Oncogenic HPV types not 16/18

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Women who have a positive oncogenic human papillomavirus (HPVHuman papillomavirus) test result for which HPV types other than 16 and/or 18 are detected (‘HPV not 16/18’), should be managed according to the recommendations in this section.

Women who have a positive oncogenic HPV test result indicating the presence of both HPV type 16 and/or 18 and other oncogenic HPV types (not 16 /18), for example, a woman whose test indicates the presence of types 16 and/or 18 and 31, or 18 and 33), should be managed as for HPV types 16/18 (see Oncogenic HPV types 16/18).

Some HPV test platforms may provide additional channels with information on some of the other oncogenic HPV types (e.g. Type 31, 33 and/or 45). For the purposes of these guidelines, these HPV types should be considered as ‘oncogenic HPV (not 16/18)’ and women with these types should be managed accordingly.

These guidelines incorporate recommended HPVHuman papillomavirus, cytology and histopathology terminology (see 3. Terminology).

Background

2016 analysis

MSACThe Australian Medical Services Advisory Committee recommended liquid-based cytology (LBCLiquid based cytology(LBC) is a way of preparing cervical samples for examination in the laboratory.) triage for women with a positive oncogenic HPV (not 16/18)Women with a positive HPV test result of other oncogenic HPV types other than types 16 and 18 detected using routine HPV testing in a pathology laboratory.,[1] but made no recommendations for subsequent management on the basis of triage LBCLiquid based cytology(LBC) is a way of preparing cervical samples for examination in the laboratory..

For some groups of women, it may be safe to delay colposcopy and monitor risk with follow-up surveillance, as distinct from women with a positive oncogenic HPV (16/18)Women with a positive HPV test result of HPV types 16 and/or 18 detected using routine HPV testing in a pathology laboratory. test result, for whom MSACThe Australian Medical Services Advisory Committee recommended immediate colposcopy (see Oncogenic HPV types 16/18).

HPV infections typically clear rapidly. Overall, an estimated 67% of infections resolve by 12 months, although the rate of resolution probably varies between age groups and by HPV type. After viral clearance (i.e. oncogenic HPV is no longer detected), women are at very low risk of significant cervical disease for the next 5 years. Therefore, if women with a positive oncogenic HPV (not 16/18)Women with a positive HPV test result of other oncogenic HPV types other than types 16 and 18 detected using routine HPV testing in a pathology laboratory. test result are not referred to colposcopy immediately, 12 months is an appropriate follow-up interval for retesting and allows for viral clearance to occur in a proportion of women.

The modelled MSACThe Australian Medical Services Advisory Committee evaluation of partial genotyping strategies made the following assumptions:

  • Women with pHSILPossible HSIL in the Australian Modified Bethesda System is broadly equivalent to ASC-H in US Bethesda system. or a higher-grade lesion on LBCLiquid based cytology(LBC) is a way of preparing cervical samples for examination in the laboratory. are referred for immediate colposcopy, irrespective of HPV type. This assumption is standard-of-care because these women are already known to be at risk of a high-grade lesion. Within the pre-renewal National Cervical Screening Program (NCSPNational Cervical Screening ProgramA joint program of the Australian, state and territory governments. It aims to reduce morbidity and mortality from cervical cancer, in a cost-effective manner through an organised approach to cervical screening. The program encourages women in the target population to have regular Pap smears.), women with pHSILPossible HSIL in the Australian Modified Bethesda System is broadly equivalent to ASC-H in US Bethesda system. are referred to immediate colposcopy.
  • Women with a positive oncogenic HPV (not 16/18)Women with a positive HPV test result of other oncogenic HPV types other than types 16 and 18 detected using routine HPV testing in a pathology laboratory. test result who have negative LBCLiquid based cytology(LBC) is a way of preparing cervical samples for examination in the laboratory. undergo follow-up surveillance at 12 months rather than immediate colposcopy.

The MSACThe Australian Medical Services Advisory Committee evaluation also modelled alternative management options for women with a LBCLiquid based cytology(LBC) is a way of preparing cervical samples for examination in the laboratory. prediction of possible low-grade intraepithelial lesion (pLSILPossible LSIL in the Australian Modified Bethesda System is broadly equivalent to ASCUS in US Bethesda system.) or low-grade intraepithelial lesion (LSILLow-grade squamous intraepithelial lesionThe low-grade squamous intraepithelial lesion (LSIL) category is the morphological correlate of productive viral infection. It is to be used when the scientist/pathologist observes changes that would have been described as ‘HPV effect’ or ‘CIN 1’ in the previous Australian terminology and represents part of the previous ‘low-grade squamous epithelial abnormality’ category.) and a positive oncogenic HPV (not 16/18)Women with a positive HPV test result of other oncogenic HPV types other than types 16 and 18 detected using routine HPV testing in a pathology laboratory. test result. These women are at intermediate risk of significant cervical abnormality (see Section 3. Terminology). MSACThe Australian Medical Services Advisory Committee did not make recommendations for the follow-up of this group of women.[1] Therefore, further systematic reviews and modelling analyses were undertaken to inform recommendations for this group. The updated modelled analysis considers the management pathways for colposcopy referral, colposcopic management, and post-treatment test-of-cure as specified in these guidelines, some of which differ from the assumptions made in the MSACThe Australian Medical Services Advisory Committee modelling. Therefore, the final modelled analysis considers the impact of changing recommendations for this group on outcomes and costs (see Section 5. Benefits, harms and cost-effectiveness of cervical screening in the renewed NCSP and Modelling reports.)

2020 analysis

In April 2020, the NCSPNational Cervical Screening ProgramA joint program of the Australian, state and territory governments. It aims to reduce morbidity and mortality from cervical cancer, in a cost-effective manner through an organised approach to cervical screening. The program encourages women in the target population to have regular Pap smears. reviewed program data relating to biopsy outcomes in women referred to colposcopy following persistent detection of oncogenic HPV (not 16/18) at their 12-month follow-up HPV test, where LBCLiquid based cytology(LBC) is a way of preparing cervical samples for examination in the laboratory. was either negative, pLSILPossible LSIL in the Australian Modified Bethesda System is broadly equivalent to ASCUS in US Bethesda system. or LSILLow-grade squamous intraepithelial lesionThe low-grade squamous intraepithelial lesion (LSIL) category is the morphological correlate of productive viral infection. It is to be used when the scientist/pathologist observes changes that would have been described as ‘HPV effect’ or ‘CIN 1’ in the previous Australian terminology and represents part of the previous ‘low-grade squamous epithelial abnormality’ category..[2]

As a result, an update was made to the management of HPV (not 16/18) – such that if HPV (not 16/18) continues to be detected at 12 months and reflex LBCLiquid based cytology(LBC) is a way of preparing cervical samples for examination in the laboratory. does not predict a possible high-grade squamous intraepithelial lesion (pHSILPossible HSIL in the Australian Modified Bethesda System is broadly equivalent to ASC-H in US Bethesda system.), high-grade squamous intraepithelial lesion (HSILHigh-grade squamous intraepithelial lesionIn the Australian context, HSIL is used to refer to a cytology predictive of a high grade precancerous lesion (AMBS 2004), or histologically confirmed high grade precancerous lesion (HSIL-CIN2 or HSIL-CIN3 as per LAST terminology).), cancer or a glandular abnormality, women can safely be retested in a further 12 months before being referred to colposcopy if HPV detection persists at that time.

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Evidence – sources and methods

Initial evidence review

Systematic reviews and modelling studies were initially undertaken to assess the comparative safety and effectiveness of different strategies based on LBCLiquid based cytology(LBC) is a way of preparing cervical samples for examination in the laboratory. triage in women with a positive oncogenic HPV (not 16/18)Women with a positive HPV test result of other oncogenic HPV types other than types 16 and 18 detected using routine HPV testing in a pathology laboratory. test result.

In the initial evaluation, for women with a positive oncogenic HPV (not 16/18)Women with a positive HPV test result of other oncogenic HPV types other than types 16 and 18 detected using routine HPV testing in a pathology laboratory. test result and LBCLiquid based cytology(LBC) is a way of preparing cervical samples for examination in the laboratory. prediction of pLSILPossible LSIL in the Australian Modified Bethesda System is broadly equivalent to ASCUS in US Bethesda system./LSILLow-grade squamous intraepithelial lesionThe low-grade squamous intraepithelial lesion (LSIL) category is the morphological correlate of productive viral infection. It is to be used when the scientist/pathologist observes changes that would have been described as ‘HPV effect’ or ‘CIN 1’ in the previous Australian terminology and represents part of the previous ‘low-grade squamous epithelial abnormality’ category., we compared the following strategies:

  • immediate colposcopy
  • 12-month follow-up and referral to colposcopy if follow-up HPV testing is positive (regardless of HPV type) at 12 months.

In the initial evaluation, for women with a positive oncogenic HPV (not 16/18)Women with a positive HPV test result of other oncogenic HPV types other than types 16 and 18 detected using routine HPV testing in a pathology laboratory. test result who do not undergo immediate colposcopy, we compared the following strategies:

  • repeated HPV testing at 12 and 24 months before returning to 5-yearly screening if negative at both follow-up tests
  • repeated HPV testing at 12 months only, before returning to 5-yearly screening if negative at 12 months.

Evidence update (non-systematic review)

In a subsequent (April 2020) evaluation of emergent National Cancer Screening RegisterA database of identifiable persons containing defined demographic and health information, established for a specific purpose. In the case of cervical screening or other cancer screening registers, the purpose includes inviting eligible persons for screening, sending reminders when they are overdue for screening, follow up of abnormalities, statistical reporting and research. (NCSRNational Cancer Screening Register) data from the renewed NCSPNational Cervical Screening ProgramA joint program of the Australian, state and territory governments. It aims to reduce morbidity and mortality from cervical cancer, in a cost-effective manner through an organised approach to cervical screening. The program encourages women in the target population to have regular Pap smears., we considered the following modification in management for women with a positive oncogenic HPV (not 16/18)Women with a positive HPV test result of other oncogenic HPV types other than types 16 and 18 detected using routine HPV testing in a pathology laboratory. test result who do not undergo immediate colposcopy, and who have a follow-up HPV testing at 12 months where the follow-up HPV test is positive for oncogenic HPV (not 16/18):[2]

  • Where reflex LBCLiquid based cytology(LBC) is a way of preparing cervical samples for examination in the laboratory. at 12 months predicts pHSILPossible HSIL in the Australian Modified Bethesda System is broadly equivalent to ASC-H in US Bethesda system., HSILHigh-grade squamous intraepithelial lesionIn the Australian context, HSIL is used to refer to a cytology predictive of a high grade precancerous lesion (AMBS 2004), or histologically confirmed high grade precancerous lesion (HSIL-CIN2 or HSIL-CIN3 as per LAST terminology)., cancer or a glandular abnormality – colposcopy referral is recommended (no change in management)
  • Where reflex LBCLiquid based cytology(LBC) is a way of preparing cervical samples for examination in the laboratory. at 12 months does not predict pHSILPossible HSIL in the Australian Modified Bethesda System is broadly equivalent to ASC-H in US Bethesda system., HSILHigh-grade squamous intraepithelial lesionIn the Australian context, HSIL is used to refer to a cytology predictive of a high grade precancerous lesion (AMBS 2004), or histologically confirmed high grade precancerous lesion (HSIL-CIN2 or HSIL-CIN3 as per LAST terminology)., cancer or a glandular abnormality – a second follow-up HPV test in a further 12 months is recommended (i.e. 24 months after the initial screen). If HPV detection persists at the second follow-up test, it is recommended that women are referred for colposcopy, regardless of the result of reflex LBCLiquid based cytology(LBC) is a way of preparing cervical samples for examination in the laboratory..

Women who may be at higher risk of harbouring a high-grade abnormality should be referred to colposcopy if HPV is detected at 12 months, regardless of the result of reflex cytology. This includes the following groups:

  • Women two or more years overdue for screening at the time of the initial screen
  • Women who identify as being of Aboriginal or Torres Strait Islander descent
  • Women age 50 years or older

There are other groups of women who fall outside these recommendations with separate guidance, including:

Evidence findings

Systematic review

The systematic literature search identified no randomised or pseudo-randomised controlled trials directly addressing either of the following:

  • the safety and effectiveness of immediate colposcopy for women with a positive oncogenic HPV (not 16/18)Women with a positive HPV test result of other oncogenic HPV types other than types 16 and 18 detected using routine HPV testing in a pathology laboratory. test result and a reflex LBCLiquid based cytology(LBC) is a way of preparing cervical samples for examination in the laboratory. prediction of pLSILPossible LSIL in the Australian Modified Bethesda System is broadly equivalent to ASCUS in US Bethesda system./LSILLow-grade squamous intraepithelial lesionThe low-grade squamous intraepithelial lesion (LSIL) category is the morphological correlate of productive viral infection. It is to be used when the scientist/pathologist observes changes that would have been described as ‘HPV effect’ or ‘CIN 1’ in the previous Australian terminology and represents part of the previous ‘low-grade squamous epithelial abnormality’ category., compared with 12 months’ delay.
  • the safety and effectiveness of repeating HPV testing after 12 and 24 months for women with a positive oncogenic HPV (not 16/18)Women with a positive HPV test result of other oncogenic HPV types other than types 16 and 18 detected using routine HPV testing in a pathology laboratory. test result and LBCLiquid based cytology(LBC) is a way of preparing cervical samples for examination in the laboratory. reported negative or with a prediction of pLSILPossible LSIL in the Australian Modified Bethesda System is broadly equivalent to ASCUS in US Bethesda system./LSILLow-grade squamous intraepithelial lesionThe low-grade squamous intraepithelial lesion (LSIL) category is the morphological correlate of productive viral infection. It is to be used when the scientist/pathologist observes changes that would have been described as ‘HPV effect’ or ‘CIN 1’ in the previous Australian terminology and represents part of the previous ‘low-grade squamous epithelial abnormality’ category., compared with repeating HPV testing at 12 months only, before returning to 5-yearly screening.

The search strategies and inclusion and exclusion criteria are described in detail in the Technical report.

In the absence of studies directly addressing these issues, an indirect approach to the literature review was planned which focussed on benchmarking (i.e. assessing the underlying risk threshold for abnormalities that may develop into cervical intraepithelial neoplasia grade 3 (CIN3) or invasive cancer, which was accepted in the pre-renewal NCSPNational Cervical Screening ProgramA joint program of the Australian, state and territory governments. It aims to reduce morbidity and mortality from cervical cancer, in a cost-effective manner through an organised approach to cervical screening. The program encourages women in the target population to have regular Pap smears. as requiring colposcopy referral). Similarly, we sought evidence on the benchmark (lower) risk level for which, in the pre-renewal NCSPNational Cervical Screening ProgramA joint program of the Australian, state and territory governments. It aims to reduce morbidity and mortality from cervical cancer, in a cost-effective manner through an organised approach to cervical screening. The program encourages women in the target population to have regular Pap smears., it was accepted that 12-month follow-up was appropriate. These ‘benchmark’ risks were compared with the risks in women in the renewed NCSPNational Cervical Screening ProgramA joint program of the Australian, state and territory governments. It aims to reduce morbidity and mortality from cervical cancer, in a cost-effective manner through an organised approach to cervical screening. The program encourages women in the target population to have regular Pap smears. with LBCLiquid based cytology(LBC) is a way of preparing cervical samples for examination in the laboratory. reported negative or with a prediction of pLSILPossible LSIL in the Australian Modified Bethesda System is broadly equivalent to ASCUS in US Bethesda system./LSILLow-grade squamous intraepithelial lesionThe low-grade squamous intraepithelial lesion (LSIL) category is the morphological correlate of productive viral infection. It is to be used when the scientist/pathologist observes changes that would have been described as ‘HPV effect’ or ‘CIN 1’ in the previous Australian terminology and represents part of the previous ‘low-grade squamous epithelial abnormality’ category. and a positive oncogenic HPV (not 16/18)Women with a positive HPV test result of other oncogenic HPV types other than types 16 and 18 detected using routine HPV testing in a pathology laboratory. test result.

Risk benchmarks were considered for women with a positive oncogenic HPV (not 16/18)Women with a positive HPV test result of other oncogenic HPV types other than types 16 and 18 detected using routine HPV testing in a pathology laboratory. test result and a reflex LBCLiquid based cytology(LBC) is a way of preparing cervical samples for examination in the laboratory. prediction of pLSILPossible LSIL in the Australian Modified Bethesda System is broadly equivalent to ASCUS in US Bethesda system./LSILLow-grade squamous intraepithelial lesionThe low-grade squamous intraepithelial lesion (LSIL) category is the morphological correlate of productive viral infection. It is to be used when the scientist/pathologist observes changes that would have been described as ‘HPV effect’ or ‘CIN 1’ in the previous Australian terminology and represents part of the previous ‘low-grade squamous epithelial abnormality’ category.:

  • 12-month follow-up benchmark: as recommended for women with LSILLow-grade squamous intraepithelial lesionThe low-grade squamous intraepithelial lesion (LSIL) category is the morphological correlate of productive viral infection. It is to be used when the scientist/pathologist observes changes that would have been described as ‘HPV effect’ or ‘CIN 1’ in the previous Australian terminology and represents part of the previous ‘low-grade squamous epithelial abnormality’ category. cytology in the pre-renewal NCSPNational Cervical Screening ProgramA joint program of the Australian, state and territory governments. It aims to reduce morbidity and mortality from cervical cancer, in a cost-effective manner through an organised approach to cervical screening. The program encourages women in the target population to have regular Pap smears..[3]
  • ColposcopyThe examination of the cervix and vagina with a magnifying instrument called a colposcope, to check for abnormalities. referral benchmark 1 (cytology prediction of pHSILPossible HSIL in the Australian Modified Bethesda System is broadly equivalent to ASC-H in US Bethesda system./HSILHigh-grade squamous intraepithelial lesionIn the Australian context, HSIL is used to refer to a cytology predictive of a high grade precancerous lesion (AMBS 2004), or histologically confirmed high grade precancerous lesion (HSIL-CIN2 or HSIL-CIN3 as per LAST terminology).): as recommended (and considered standard-of-care) in the pre-renewal NCSPNational Cervical Screening ProgramA joint program of the Australian, state and territory governments. It aims to reduce morbidity and mortality from cervical cancer, in a cost-effective manner through an organised approach to cervical screening. The program encourages women in the target population to have regular Pap smears.[3]
  • ColposcopyThe examination of the cervix and vagina with a magnifying instrument called a colposcope, to check for abnormalities. referral benchmark 2 (positive oncogenic HPV (16/18)Women with a positive HPV test result of HPV types 16 and/or 18 detected using routine HPV testing in a pathology laboratory. test result): as recommended by MSACThe Australian Medical Services Advisory Committee in the renewed NCSPNational Cervical Screening ProgramA joint program of the Australian, state and territory governments. It aims to reduce morbidity and mortality from cervical cancer, in a cost-effective manner through an organised approach to cervical screening. The program encourages women in the target population to have regular Pap smears..

Systematic reviews were performed to identify studies examining the risk for the development of CIN3+ (CIN 3Severe dysplasia to carcinoma in situ (The term CIN 2+ refers to CIN 2, 3, or invasive cervical cancer; CIN3+ refers to CIN 3 or invasive cervical cancer) or invasive cervical cancer) among women with a positive oncogenic HPV (not 16/18)Women with a positive HPV test result of other oncogenic HPV types other than types 16 and 18 detected using routine HPV testing in a pathology laboratory. test result and pLSILPossible LSIL in the Australian Modified Bethesda System is broadly equivalent to ASCUS in US Bethesda system./LSILLow-grade squamous intraepithelial lesionThe low-grade squamous intraepithelial lesion (LSIL) category is the morphological correlate of productive viral infection. It is to be used when the scientist/pathologist observes changes that would have been described as ‘HPV effect’ or ‘CIN 1’ in the previous Australian terminology and represents part of the previous ‘low-grade squamous epithelial abnormality’ category. cytology, compared with each of the following groups:

  • women with cytological prediction of pLSILPossible LSIL in the Australian Modified Bethesda System is broadly equivalent to ASCUS in US Bethesda system./LSILLow-grade squamous intraepithelial lesionThe low-grade squamous intraepithelial lesion (LSIL) category is the morphological correlate of productive viral infection. It is to be used when the scientist/pathologist observes changes that would have been described as ‘HPV effect’ or ‘CIN 1’ in the previous Australian terminology and represents part of the previous ‘low-grade squamous epithelial abnormality’ category., regardless of HPV status
  • women with cytological prediction of pHSILPossible HSIL in the Australian Modified Bethesda System is broadly equivalent to ASC-H in US Bethesda system./HSILHigh-grade squamous intraepithelial lesionIn the Australian context, HSIL is used to refer to a cytology predictive of a high grade precancerous lesion (AMBS 2004), or histologically confirmed high grade precancerous lesion (HSIL-CIN2 or HSIL-CIN3 as per LAST terminology)., regardless of HPV status
  • women with a positive oncogenic HPV (16/18)Women with a positive HPV test result of HPV types 16 and/or 18 detected using routine HPV testing in a pathology laboratory. test result, regardless of cytology status.

The search strategies and findings are described in detail in the Technical report.

Searches identified six relevant prospective cohort studies (level II evidence): two longitudinal studies[4][5] and four studies that reported results for outcomes on immediate colposcopy.[6][7][8][9][10][11][12][13][14] None of these studies were specifically designed to compare the risks associated with specific oncogenic HPV genotypes and specific cytology findings. As a result, it was not possible to determine whether subgroups with oncogenic HPV types (not 16/18), pLSILPossible LSIL in the Australian Modified Bethesda System is broadly equivalent to ASCUS in US Bethesda system. or LSILLow-grade squamous intraepithelial lesionThe low-grade squamous intraepithelial lesion (LSIL) category is the morphological correlate of productive viral infection. It is to be used when the scientist/pathologist observes changes that would have been described as ‘HPV effect’ or ‘CIN 1’ in the previous Australian terminology and represents part of the previous ‘low-grade squamous epithelial abnormality’ category. were similar to benchmark groups or to control for confounding factors such as smoking. Therefore, all six studies were assessed to have a high risk of bias.

Both longitudinal studies reported CIN3+ risks associated with oncogenic HPV (not 16/18), LSILLow-grade squamous intraepithelial lesionThe low-grade squamous intraepithelial lesion (LSIL) category is the morphological correlate of productive viral infection. It is to be used when the scientist/pathologist observes changes that would have been described as ‘HPV effect’ or ‘CIN 1’ in the previous Australian terminology and represents part of the previous ‘low-grade squamous epithelial abnormality’ category. cytology and, for the benchmark for 12-month follow-up, all LSILLow-grade squamous intraepithelial lesionThe low-grade squamous intraepithelial lesion (LSIL) category is the morphological correlate of productive viral infection. It is to be used when the scientist/pathologist observes changes that would have been described as ‘HPV effect’ or ‘CIN 1’ in the previous Australian terminology and represents part of the previous ‘low-grade squamous epithelial abnormality’ category. cytology, regardless of HPV status. In one study women were actively followed up for 2 years and underwent an exit colposcopy,[4] and in the other women were passively followed-up for a maximum of 18 years.[5]

Two studies[6][7][8][9][10][14] reported CIN3+ risks on immediate colposcopy for women with a positive oncogenic HPV (not 16/18)Women with a positive HPV test result of other oncogenic HPV types other than types 16 and 18 detected using routine HPV testing in a pathology laboratory. test result, pLSILPossible LSIL in the Australian Modified Bethesda System is broadly equivalent to ASCUS in US Bethesda system. (ASC-USAtypical squamous cells, undetermined significance, Bethesda 2001) or LSILLow-grade squamous intraepithelial lesionThe low-grade squamous intraepithelial lesion (LSIL) category is the morphological correlate of productive viral infection. It is to be used when the scientist/pathologist observes changes that would have been described as ‘HPV effect’ or ‘CIN 1’ in the previous Australian terminology and represents part of the previous ‘low-grade squamous epithelial abnormality’ category. cytology and the benchmarks for immediate colposcopy (pHSILPossible HSIL in the Australian Modified Bethesda System is broadly equivalent to ASC-H in US Bethesda system./HSILHigh-grade squamous intraepithelial lesionIn the Australian context, HSIL is used to refer to a cytology predictive of a high grade precancerous lesion (AMBS 2004), or histologically confirmed high grade precancerous lesion (HSIL-CIN2 or HSIL-CIN3 as per LAST terminology). cytology or positive HPV (16/18) test result), as well as the benchmark for 12-month follow-up (all LSILLow-grade squamous intraepithelial lesionThe low-grade squamous intraepithelial lesion (LSIL) category is the morphological correlate of productive viral infection. It is to be used when the scientist/pathologist observes changes that would have been described as ‘HPV effect’ or ‘CIN 1’ in the previous Australian terminology and represents part of the previous ‘low-grade squamous epithelial abnormality’ category.).

The findings of these studies showed the following:

  • For women with a positive oncogenic HPV (not 16/18)Women with a positive HPV test result of other oncogenic HPV types other than types 16 and 18 detected using routine HPV testing in a pathology laboratory. test result and a cytological prediction of LSILLow-grade squamous intraepithelial lesionThe low-grade squamous intraepithelial lesion (LSIL) category is the morphological correlate of productive viral infection. It is to be used when the scientist/pathologist observes changes that would have been described as ‘HPV effect’ or ‘CIN 1’ in the previous Australian terminology and represents part of the previous ‘low-grade squamous epithelial abnormality’ category., the risk of CIN3+ was lower than that for the 12-month follow-up benchmark (LSILLow-grade squamous intraepithelial lesionThe low-grade squamous intraepithelial lesion (LSIL) category is the morphological correlate of productive viral infection. It is to be used when the scientist/pathologist observes changes that would have been described as ‘HPV effect’ or ‘CIN 1’ in the previous Australian terminology and represents part of the previous ‘low-grade squamous epithelial abnormality’ category. cytology, regardless of HPV status):
  • over 2 years in cohorts age >18 years or >30 years at baseline
  • after 18 years in a cohort age >16 years at baseline.
  • For women with a positive oncogenic HPV (not 16/18)Women with a positive HPV test result of other oncogenic HPV types other than types 16 and 18 detected using routine HPV testing in a pathology laboratory. test result and a cytological prediction of pLSILPossible LSIL in the Australian Modified Bethesda System is broadly equivalent to ASCUS in US Bethesda system./LSILLow-grade squamous intraepithelial lesionThe low-grade squamous intraepithelial lesion (LSIL) category is the morphological correlate of productive viral infection. It is to be used when the scientist/pathologist observes changes that would have been described as ‘HPV effect’ or ‘CIN 1’ in the previous Australian terminology and represents part of the previous ‘low-grade squamous epithelial abnormality’ category., the risk of CIN3+ diagnosed on immediate colposcopy was consistently less than half the risk for the immediate colposcopy benchmarks (cytological prediction of pHSILPossible HSIL in the Australian Modified Bethesda System is broadly equivalent to ASC-H in US Bethesda system./HSILHigh-grade squamous intraepithelial lesionIn the Australian context, HSIL is used to refer to a cytology predictive of a high grade precancerous lesion (AMBS 2004), or histologically confirmed high grade precancerous lesion (HSIL-CIN2 or HSIL-CIN3 as per LAST terminology). or positive oncogenic HPV (16/18)Women with a positive HPV test result of HPV types 16 and/or 18 detected using routine HPV testing in a pathology laboratory. test result) and similar to (if not less than) the 12-month follow-up benchmark (cytological prediction of LSILLow-grade squamous intraepithelial lesionThe low-grade squamous intraepithelial lesion (LSIL) category is the morphological correlate of productive viral infection. It is to be used when the scientist/pathologist observes changes that would have been described as ‘HPV effect’ or ‘CIN 1’ in the previous Australian terminology and represents part of the previous ‘low-grade squamous epithelial abnormality’ category., regardless of HPV status) in cohorts age >25 years, >21 years or >18 years at baseline.

A second systematic review was performed to identify studies examining the risk of CIN3 or higher-grade lesion among women undergoing routine cervical screening with a positive oncogenic HPV (not 16/18)Women with a positive HPV test result of other oncogenic HPV types other than types 16 and 18 detected using routine HPV testing in a pathology laboratory. test result and negative cytology, compared with the following groups:

  • 12-month follow-up benchmark (women with a cytological prediction of pLSILPossible LSIL in the Australian Modified Bethesda System is broadly equivalent to ASCUS in US Bethesda system./LSILLow-grade squamous intraepithelial lesionThe low-grade squamous intraepithelial lesion (LSIL) category is the morphological correlate of productive viral infection. It is to be used when the scientist/pathologist observes changes that would have been described as ‘HPV effect’ or ‘CIN 1’ in the previous Australian terminology and represents part of the previous ‘low-grade squamous epithelial abnormality’ category., regardless of HPV status)
  • women with a cytological prediction of pLSILPossible LSIL in the Australian Modified Bethesda System is broadly equivalent to ASCUS in US Bethesda system./LSILLow-grade squamous intraepithelial lesionThe low-grade squamous intraepithelial lesion (LSIL) category is the morphological correlate of productive viral infection. It is to be used when the scientist/pathologist observes changes that would have been described as ‘HPV effect’ or ‘CIN 1’ in the previous Australian terminology and represents part of the previous ‘low-grade squamous epithelial abnormality’ category. and a positive oncogenic HPV (not 16/18)Women with a positive HPV test result of other oncogenic HPV types other than types 16 and 18 detected using routine HPV testing in a pathology laboratory. test result.

No studies that met inclusion criteria were identified. The search strategy and findings are described in detail in the Technical report.

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Modelling

The findings of the systematic review confirmed that a modelled analysis was required to assess the safety and effectiveness of immediate colposcopy, compared with returning in 12 months for a repeat HPV test, for women with a positive oncogenic HPV (not 16/18)Women with a positive HPV test result of other oncogenic HPV types other than types 16 and 18 detected using routine HPV testing in a pathology laboratory. test result and reflex LBCLiquid based cytology(LBC) is a way of preparing cervical samples for examination in the laboratory. prediction of pLSILPossible LSIL in the Australian Modified Bethesda System is broadly equivalent to ASCUS in US Bethesda system./LSILLow-grade squamous intraepithelial lesionThe low-grade squamous intraepithelial lesion (LSIL) category is the morphological correlate of productive viral infection. It is to be used when the scientist/pathologist observes changes that would have been described as ‘HPV effect’ or ‘CIN 1’ in the previous Australian terminology and represents part of the previous ‘low-grade squamous epithelial abnormality’ category. at triage. The modelling study assessed the population-level effects of alternative strategies, within a national program of primary HPV screening with partial genotyping, for women with a positive oncogenic HPV (not 16/18)Women with a positive HPV test result of other oncogenic HPV types other than types 16 and 18 detected using routine HPV testing in a pathology laboratory. test result and reflex LBCLiquid based cytology(LBC) is a way of preparing cervical samples for examination in the laboratory. prediction of pLSILPossible LSIL in the Australian Modified Bethesda System is broadly equivalent to ASCUS in US Bethesda system./LSILLow-grade squamous intraepithelial lesionThe low-grade squamous intraepithelial lesion (LSIL) category is the morphological correlate of productive viral infection. It is to be used when the scientist/pathologist observes changes that would have been described as ‘HPV effect’ or ‘CIN 1’ in the previous Australian terminology and represents part of the previous ‘low-grade squamous epithelial abnormality’ category.. Modelling was performed for HPV-unvaccinated women and for cohorts offered vaccination.

Options compared in women with a positive oncogenic HPV (not 16/18)Women with a positive HPV test result of other oncogenic HPV types other than types 16 and 18 detected using routine HPV testing in a pathology laboratory. test result and reflex LBCLiquid based cytology(LBC) is a way of preparing cervical samples for examination in the laboratory. prediction of pLSILPossible LSIL in the Australian Modified Bethesda System is broadly equivalent to ASCUS in US Bethesda system./LSILLow-grade squamous intraepithelial lesionThe low-grade squamous intraepithelial lesion (LSIL) category is the morphological correlate of productive viral infection. It is to be used when the scientist/pathologist observes changes that would have been described as ‘HPV effect’ or ‘CIN 1’ in the previous Australian terminology and represents part of the previous ‘low-grade squamous epithelial abnormality’ category.

Comparison 1:

  • (Option A) follow-up with HPV testing in 12 months, followed by colposcopy for those with a positive oncogenic HPV (any type)Women with a positive HPV test result of any oncogenic HPV types detected using routine HPV testing in a pathology laboratory. test result at 12 months, or return to routine 5-yearly screening if oncogenic HPV not detectedOncogenic HPV types not detected by the HPV testing platform. at 12 months
  • (Option B) referral to colposcopy.

Comparison 2:

  • (Option A) as above
  • (Option C) referral to follow-up with HPV testing in 12 months and 24 months, with immediate colposcopy for those with a positive oncogenic HPV (any type)Women with a positive HPV test result of any oncogenic HPV types detected using routine HPV testing in a pathology laboratory. test result at either follow-up test, or return to routine 5-yearly screening if oncogenic HPV not detectedOncogenic HPV types not detected by the HPV testing platform. at both follow-up tests.

Summary of findings

The findings are described in detail in the Modelling reports.

Comparison 1: 12-month follow-up versus immediate colposcopy

Modelling comparing 12-month follow-up with immediate referral to colposcopy in women with a positive oncogenic HPV (not 16/18)Women with a positive HPV test result of other oncogenic HPV types other than types 16 and 18 detected using routine HPV testing in a pathology laboratory. test result and reflex LBCLiquid based cytology(LBC) is a way of preparing cervical samples for examination in the laboratory. prediction of pLSILPossible LSIL in the Australian Modified Bethesda System is broadly equivalent to ASCUS in US Bethesda system./LSILLow-grade squamous intraepithelial lesionThe low-grade squamous intraepithelial lesion (LSIL) category is the morphological correlate of productive viral infection. It is to be used when the scientist/pathologist observes changes that would have been described as ‘HPV effect’ or ‘CIN 1’ in the previous Australian terminology and represents part of the previous ‘low-grade squamous epithelial abnormality’ category. predicted the following:

  • For women in this group undergoing 12-month follow-up (Option A), the 20-year risk of developing invasive cervical cancer (Figure 6.1) is lower than the risk for women with a screening cytology prediction of LSILLow-grade squamous intraepithelial lesionThe low-grade squamous intraepithelial lesion (LSIL) category is the morphological correlate of productive viral infection. It is to be used when the scientist/pathologist observes changes that would have been described as ‘HPV effect’ or ‘CIN 1’ in the previous Australian terminology and represents part of the previous ‘low-grade squamous epithelial abnormality’ category. in the pre-renewal NCSPNational Cervical Screening ProgramA joint program of the Australian, state and territory governments. It aims to reduce morbidity and mortality from cervical cancer, in a cost-effective manner through an organised approach to cervical screening. The program encourages women in the target population to have regular Pap smears. (i.e. lower than the accepted benchmark risk for 12-month follow-up in Australia).
  • The renewed NCSPNational Cervical Screening ProgramA joint program of the Australian, state and territory governments. It aims to reduce morbidity and mortality from cervical cancer, in a cost-effective manner through an organised approach to cervical screening. The program encourages women in the target population to have regular Pap smears., incorporating 12-month follow-up for women in this group (and incorporating other recommendations in these guidelines), is predicted to reduce cervical cancer incidence and mortality by 31–36% in unvaccinated cohorts and 24–29% in cohorts offered vaccination, compared with the pre-renewal NCSPNational Cervical Screening ProgramA joint program of the Australian, state and territory governments. It aims to reduce morbidity and mortality from cervical cancer, in a cost-effective manner through an organised approach to cervical screening. The program encourages women in the target population to have regular Pap smears..
  • The renewed NCSPNational Cervical Screening ProgramA joint program of the Australian, state and territory governments. It aims to reduce morbidity and mortality from cervical cancer, in a cost-effective manner through an organised approach to cervical screening. The program encourages women in the target population to have regular Pap smears., incorporating immediate colposcopy for women in this group (and incorporating other recommendations in these guidelines), is predicted to reduce cervical cancer incidence and mortality by 32–37% in unvaccinated cohorts and 27–32% in cohorts offered vaccination, compared with the pre-renewal NCSPNational Cervical Screening ProgramA joint program of the Australian, state and territory governments. It aims to reduce morbidity and mortality from cervical cancer, in a cost-effective manner through an organised approach to cervical screening. The program encourages women in the target population to have regular Pap smears..
  • For women in this group, immediate referral to colposcopy provides an incremental 1–3% reduction in cervical cancer incidence and mortality, compared with 12-month follow-up. However, colposcopy referral for this group substantially increases the number of colposcopies in the renewed NCSPNational Cervical Screening ProgramA joint program of the Australian, state and territory governments. It aims to reduce morbidity and mortality from cervical cancer, in a cost-effective manner through an organised approach to cervical screening. The program encourages women in the target population to have regular Pap smears., with more than 650 colposcopies required to avert an additional case of cervical cancer, compared with 12-month follow-up.
  • ColposcopyThe examination of the cervix and vagina with a magnifying instrument called a colposcope, to check for abnormalities. referral for this group would be very cost-ineffective, with an incremental cost-effectiveness ratio of >$100,000 per life-year saved (LYS), compared with 12-month follow-up.
  • ColposcopyThe examination of the cervix and vagina with a magnifying instrument called a colposcope, to check for abnormalities. referral of only women age >45 years in this group, however, is more cost-effective, with an incremental cost-effectiveness ratio of $40,000/LYS (95% credible interval (CrI): $37,000–42,000/LYS) in unvaccinated cohorts, and $41,000/LYS (95% CrI: $38,000–44,000/LYS) in cohorts offered vaccination.

Figure 6.1. Predicted 20-year risk of cervical cancer in women with a positive oncogenic HPV (not 16/18)Women with a positive HPV test result of other oncogenic HPV types other than types 16 and 18 detected using routine HPV testing in a pathology laboratory. test result and a reflex LBCLiquid based cytology(LBC) is a way of preparing cervical samples for examination in the laboratory. prediction of pLSILPossible LSIL in the Australian Modified Bethesda System is broadly equivalent to ASCUS in US Bethesda system./LSILLow-grade squamous intraepithelial lesionThe low-grade squamous intraepithelial lesion (LSIL) category is the morphological correlate of productive viral infection. It is to be used when the scientist/pathologist observes changes that would have been described as ‘HPV effect’ or ‘CIN 1’ in the previous Australian terminology and represents part of the previous ‘low-grade squamous epithelial abnormality’ category.

Figure 6.1

Note: The black horizontal line in each figure indicates the risk under the pre-renewal NCSPNational Cervical Screening ProgramA joint program of the Australian, state and territory governments. It aims to reduce morbidity and mortality from cervical cancer, in a cost-effective manner through an organised approach to cervical screening. The program encourages women in the target population to have regular Pap smears. for women with a cytological prediction of LSILLow-grade squamous intraepithelial lesionThe low-grade squamous intraepithelial lesion (LSIL) category is the morphological correlate of productive viral infection. It is to be used when the scientist/pathologist observes changes that would have been described as ‘HPV effect’ or ‘CIN 1’ in the previous Australian terminology and represents part of the previous ‘low-grade squamous epithelial abnormality’ category. at a routine screening visit and a negative cytology test in the previous 2 years.

Comparison 2: follow-up options (12 and 24 months versus 12 months only)

Modelling comparing follow-up at both 12 months and 24 months, with 12-month follow-up only, in women with a positive oncogenic HPV (not 16/18)Women with a positive HPV test result of other oncogenic HPV types other than types 16 and 18 detected using routine HPV testing in a pathology laboratory. test result and reflex LBCLiquid based cytology(LBC) is a way of preparing cervical samples for examination in the laboratory. prediction of pLSILPossible LSIL in the Australian Modified Bethesda System is broadly equivalent to ASCUS in US Bethesda system./LSILLow-grade squamous intraepithelial lesionThe low-grade squamous intraepithelial lesion (LSIL) category is the morphological correlate of productive viral infection. It is to be used when the scientist/pathologist observes changes that would have been described as ‘HPV effect’ or ‘CIN 1’ in the previous Australian terminology and represents part of the previous ‘low-grade squamous epithelial abnormality’ category. at index screening visit predicted the following:

  • Performing both 12-month and 24-month follow-up results in <1% difference in cervical cancer incidence and mortality and <1% difference in colposcopies, compared with 12-month follow-up only.
  • Performing both 12-month and 24-month follow-up for this group would be very cost-ineffective, with an incremental cost-effectiveness ratio of >$300,000/LYS, compared with 12-month follow-up only.
  • Limiting both 12-month and 24-month follow-up to women over 55 in this group remains cost-ineffective compared with 12-month follow-up only. The incremental cost-effectiveness ratio is >$65,000/LYS if 12-month and 24-month follow-up is used in women age over 55 years, compared with performing 12-month follow-up only for women of all ages.

The detailed description of the model assumptions, calibration and findings are provided in the Modelling reports.

Although the update to these Guidelines in 2020 for the management of intermediate risk women who remain HPV positiveWomen with a positive HPV test result of any oncogenic HPV types detected using HPV testing platforms in a pathology laboratory. at 12/24 months was not explicitly modelled, based on the 2020 NCSRNational Cancer Screening Register data analysis (see below), the overall population-level benefits modelled for the renewed NCSPNational Cervical Screening ProgramA joint program of the Australian, state and territory governments. It aims to reduce morbidity and mortality from cervical cancer, in a cost-effective manner through an organised approach to cervical screening. The program encourages women in the target population to have regular Pap smears. compared with the pre-renewed NCSPNational Cervical Screening ProgramA joint program of the Australian, state and territory governments. It aims to reduce morbidity and mortality from cervical cancer, in a cost-effective manner through an organised approach to cervical screening. The program encourages women in the target population to have regular Pap smears., are likely to be similar to those originally modelled.

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Review of NCSPNational Cervical Screening ProgramA joint program of the Australian, state and territory governments. It aims to reduce morbidity and mortality from cervical cancer, in a cost-effective manner through an organised approach to cervical screening. The program encourages women in the target population to have regular Pap smears. data

In 2020, a review of the first 2 years of the renewed NCSPNational Cervical Screening ProgramA joint program of the Australian, state and territory governments. It aims to reduce morbidity and mortality from cervical cancer, in a cost-effective manner through an organised approach to cervical screening. The program encourages women in the target population to have regular Pap smears. was conducted on data for women classified as having higher or intermediate risk of cervical cancer on their baseline Cervical Screening Test with subsequent colposcopy and/or histology recorded on the NCSRNational Cancer Screening Register. The following data were included:

  • all results for women at higher risk and intermediate risk from 1 December 2017 to 31 December 2019 (data extracted 14 January 2020)
  • all colposcopy assessment and MBS forms coded and completed by the NCSRNational Cancer Screening Register relating to visits up to 16 April 2020 (data extracted 22 September 2020)
  • and all histology assessment and MBS forms coded and completed by the NCSRNational Cancer Screening Register relating to samples collected up to 16 April 2020 (data extracted 22 September 2020).

For benchmarking, the outcomes for intermediate risk women whose follow-up test result is HPV (not 16/18) were compared with outcomes in those women at higher risk at baseline (Tables 6.1, 6.2).[2]
Table 6.1. Outcomes for higher-risk group according to baseline test (based on April 2020 NCSRNational Cancer Screening Register data)

Baseline test result Histologically

confirmed CIN2+

Histologically

confirmed CIN3+

Invasive

cervical cancer

HPV 16/18Only HPV types 16 and or 18 detected using routine HPV screening tests in laboratory. 17.8–19.5% 12.6–14.0% 0.88–0.96%
HPV (not 16/18) and LBCLiquid based cytology(LBC) is a way of preparing cervical samples for examination in the laboratory. prediction

pHSILPossible HSIL in the Australian Modified Bethesda System is broadly equivalent to ASC-H in US Bethesda system., HSILHigh-grade squamous intraepithelial lesionIn the Australian context, HSIL is used to refer to a cytology predictive of a high grade precancerous lesion (AMBS 2004), or histologically confirmed high grade precancerous lesion (HSIL-CIN2 or HSIL-CIN3 as per LAST terminology)., or glandular

55.4–58.6% 35.9–38.5% 0.66–0.76%
Source: National Cervical Screening Program[2]
Ranges reflect variation depending on whether or not histological outcomes are restricted to occurring within 6 months of referral.

Table 6.2. Outcomes for women initially at intermediate risk, whose follow-up test result is HPV (not 16/18), according to LBCLiquid based cytology(LBC) is a way of preparing cervical samples for examination in the laboratory. prediction at follow-up test (based on April 2020 NCSRNational Cancer Screening Register data)
LBCLiquid based cytology(LBC) is a way of preparing cervical samples for examination in the laboratory. prediction Histologically

confirmed CIN2+

Histologically

confirmed CIN3+

Invasive

cervical cancer

pHSILPossible HSIL in the Australian Modified Bethesda System is broadly equivalent to ASC-H in US Bethesda system., HSILHigh-grade squamous intraepithelial lesionIn the Australian context, HSIL is used to refer to a cytology predictive of a high grade precancerous lesion (AMBS 2004), or histologically confirmed high grade precancerous lesion (HSIL-CIN2 or HSIL-CIN3 as per LAST terminology)., or glandular 54.1–55.8% 32.1–33.8% 0.32–0.37%
negative, pLSILPossible LSIL in the Australian Modified Bethesda System is broadly equivalent to ASCUS in US Bethesda system. or LSILLow-grade squamous intraepithelial lesionThe low-grade squamous intraepithelial lesion (LSIL) category is the morphological correlate of productive viral infection. It is to be used when the scientist/pathologist observes changes that would have been described as ‘HPV effect’ or ‘CIN 1’ in the previous Australian terminology and represents part of the previous ‘low-grade squamous epithelial abnormality’ category. 8.1–8.5% 3.1–3.4% 0.01–0.02%
Source: National Cervical Screening Program[2]
Ranges reflect variation depending on whether or not histological outcomes are restricted to occurring within 6 months of referral.

The analysis shows that, compared with other groups who are referred for colposcopy, the risk of CIN2+, CIN3+ and cervical cancer are much lower for women at intermediate risk whose follow-up test is HPV (not 16/18) and who have an LBCLiquid based cytology(LBC) is a way of preparing cervical samples for examination in the laboratory. prediction of negative, pLSILPossible LSIL in the Australian Modified Bethesda System is broadly equivalent to ASCUS in US Bethesda system. or LSILLow-grade squamous intraepithelial lesionThe low-grade squamous intraepithelial lesion (LSIL) category is the morphological correlate of productive viral infection. It is to be used when the scientist/pathologist observes changes that would have been described as ‘HPV effect’ or ‘CIN 1’ in the previous Australian terminology and represents part of the previous ‘low-grade squamous epithelial abnormality’ category.. Within this group of women, we compared risks for women age <50 years with those for women age 50 years or older (Table 6.3).[2]

Table 6.3. Outcomes for women initially at intermediate risk, whose follow-up test result is (HPV (not 16/18), and LBCLiquid based cytology(LBC) is a way of preparing cervical samples for examination in the laboratory. prediction is negative, pLSILPossible LSIL in the Australian Modified Bethesda System is broadly equivalent to ASCUS in US Bethesda system. or LSILLow-grade squamous intraepithelial lesionThe low-grade squamous intraepithelial lesion (LSIL) category is the morphological correlate of productive viral infection. It is to be used when the scientist/pathologist observes changes that would have been described as ‘HPV effect’ or ‘CIN 1’ in the previous Australian terminology and represents part of the previous ‘low-grade squamous epithelial abnormality’ category., according to age (based on April 2020 NCSRNational Cancer Screening Register data)

Age Histologically

confirmed CIN2+

Histologically

confirmed CIN3+

Invasive

cervical cancer

<50 years 10.08% 4.0% 0.02%
≥50 years 3.4% 1.5% No cases identified
Source: National Cervical Screening Program[2]

It should be noted that women 50 years or older who are HPV positiveWomen with a positive HPV test result of any oncogenic HPV types detected using HPV testing platforms in a pathology laboratory. without a visible lesion at colposcopy, are at higher risk of harbouring a covert abnormality in the canal (compared to younger women who are HPV positiveWomen with a positive HPV test result of any oncogenic HPV types detected using HPV testing platforms in a pathology laboratory.). Considering this issue, and applying the precautionary principle, among women at intermediate risk whose follow-up test is HPV (non 16/18), LBCLiquid based cytology(LBC) is a way of preparing cervical samples for examination in the laboratory. prediction negative, pLSILPossible LSIL in the Australian Modified Bethesda System is broadly equivalent to ASCUS in US Bethesda system. or LSILLow-grade squamous intraepithelial lesionThe low-grade squamous intraepithelial lesion (LSIL) category is the morphological correlate of productive viral infection. It is to be used when the scientist/pathologist observes changes that would have been described as ‘HPV effect’ or ‘CIN 1’ in the previous Australian terminology and represents part of the previous ‘low-grade squamous epithelial abnormality’ category., direct referral to coloscopy should still be recommended for women 50 years of age or over. It is important to note that older women referred to colposcopy on this basis, who are likely to have a type 3 TZTransformation zoneThis region of the cervix where the columnar epithelium has been replaced and/or is being replaced by the new metaplastic squamous epithelium is referred to as the transformation zone. It corresponds to the area of cervix bound by the original squamocolumnar junction at the distal end and proximally by the furthest extent that squamous metaplasia has occurred as defined by the new squamocolumnar junction. In premenopausal women, the transformation zone is fully located on the ectocervix. After menopause through old age, the cervix shrinks with the decreasing levels of estrogen. Consequently, the transformation zone may move partially, and later fully, into the cervical canal.The transformation zone may be described as normal when it is composed of immature and/or mature squamous metaplasia along with intervening areas or islands of columnar epithelium, with no signs of cervical carcinogenesis. It is termed an abnormal or atypical transformation zone (ATZ) when evidence of cervical carcinogenesis such as dysplastic change is observed in the transformation zone. Identifying the transformation zone is of great importance in colposcopy, as almost all manifestations of cervical carcinogenesis occur in this zone., not undergo diagnostic excision of the TZTransformation zoneThis region of the cervix where the columnar epithelium has been replaced and/or is being replaced by the new metaplastic squamous epithelium is referred to as the transformation zone. It corresponds to the area of cervix bound by the original squamocolumnar junction at the distal end and proximally by the furthest extent that squamous metaplasia has occurred as defined by the new squamocolumnar junction. In premenopausal women, the transformation zone is fully located on the ectocervix. After menopause through old age, the cervix shrinks with the decreasing levels of estrogen. Consequently, the transformation zone may move partially, and later fully, into the cervical canal.The transformation zone may be described as normal when it is composed of immature and/or mature squamous metaplasia along with intervening areas or islands of columnar epithelium, with no signs of cervical carcinogenesis. It is termed an abnormal or atypical transformation zone (ATZ) when evidence of cervical carcinogenesis such as dysplastic change is observed in the transformation zone. Identifying the transformation zone is of great importance in colposcopy, as almost all manifestations of cervical carcinogenesis occur in this zone. without histological or cytological evidence of a high-grade lesion (see Recommendation 8.12).

Additionally, other groups of women may be at higher risk of harbouring a high-grade abnormality, and again applying the precautionary principle, among women at intermediate risk whose follow-up test is HPV (non 16/18), LBCLiquid based cytology(LBC) is a way of preparing cervical samples for examination in the laboratory. prediction negative, pLSILPossible LSIL in the Australian Modified Bethesda System is broadly equivalent to ASCUS in US Bethesda system. or LSILLow-grade squamous intraepithelial lesionThe low-grade squamous intraepithelial lesion (LSIL) category is the morphological correlate of productive viral infection. It is to be used when the scientist/pathologist observes changes that would have been described as ‘HPV effect’ or ‘CIN 1’ in the previous Australian terminology and represents part of the previous ‘low-grade squamous epithelial abnormality’ category., direct referral to coloscopy should still be recommended for:

  • Women two or more years overdue for screening at the time of the initial Cervical Screening Test
  • Women who identify as being of Aboriginal or Torres Strait Islander descent

Women who identify as being of Aboriginal or Torres Strait Islander descent are known to have higher rates of cervical cancer incidence and mortality. There is a paucity of program-wide data on risk of high-grade abnormalities in Aboriginal or Torres Strait Islander women, due to a historical lack of data on Indigenous status in screening registers and continuing low levels of completeness of this information on the National Cancer Screening RegisterA database of identifiable persons containing defined demographic and health information, established for a specific purpose. In the case of cervical screening or other cancer screening registers, the purpose includes inviting eligible persons for screening, sending reminders when they are overdue for screening, follow up of abnormalities, statistical reporting and research.. Data from population-based linked health records in Queensland, however, document a higher risk of high-grade histological abnormalities among Aboriginal or Torres Strait Islander women (OR 2.0, 95% CI 1.9–2.1).[15]

Note that there are other groups of women who fall outside these recommendations as there are separate guidelines specifically for them, including:

Evidence summary and recommendations

Evidence summary Level References
Data from two prospective cohort studies indicate that women with a cytological prediction of LSILLow-grade squamous intraepithelial lesionThe low-grade squamous intraepithelial lesion (LSIL) category is the morphological correlate of productive viral infection. It is to be used when the scientist/pathologist observes changes that would have been described as ‘HPV effect’ or ‘CIN 1’ in the previous Australian terminology and represents part of the previous ‘low-grade squamous epithelial abnormality’ category. in whom HPV 16/18Only HPV types 16 and or 18 detected using routine HPV screening tests in laboratory. is not detected, but have a positive oncogenic HPV (not 16/18)Women with a positive HPV test result of other oncogenic HPV types other than types 16 and 18 detected using routine HPV testing in a pathology laboratory. test result at lower risk for CIN3+ over 2 years (and for up to approximately 18 years) than women with a cytology prediction of LSILLow-grade squamous intraepithelial lesionThe low-grade squamous intraepithelial lesion (LSIL) category is the morphological correlate of productive viral infection. It is to be used when the scientist/pathologist observes changes that would have been described as ‘HPV effect’ or ‘CIN 1’ in the previous Australian terminology and represents part of the previous ‘low-grade squamous epithelial abnormality’ category., regardless of HPV status (who are referred to 12-month follow-up within the pre-renewal NCSPNational Cervical Screening ProgramA joint program of the Australian, state and territory governments. It aims to reduce morbidity and mortality from cervical cancer, in a cost-effective manner through an organised approach to cervical screening. The program encourages women in the target population to have regular Pap smears.). II [4], [5]
No longitudinal studies were found that reported the subsequent risks of CIN3+ for women with normal cytology in whom HPV 16/18Only HPV types 16 and or 18 detected using routine HPV screening tests in laboratory. is not detected, have a positive oncogenic HPV (not 16/18)Women with a positive HPV test result of other oncogenic HPV types other than types 16 and 18 detected using routine HPV testing in a pathology laboratory. test result, compared with either of the following groups:
  • women with a cytological prediction of pLSILPossible LSIL in the Australian Modified Bethesda System is broadly equivalent to ASCUS in US Bethesda system./LSILLow-grade squamous intraepithelial lesionThe low-grade squamous intraepithelial lesion (LSIL) category is the morphological correlate of productive viral infection. It is to be used when the scientist/pathologist observes changes that would have been described as ‘HPV effect’ or ‘CIN 1’ in the previous Australian terminology and represents part of the previous ‘low-grade squamous epithelial abnormality’ category., regardless of HPV status
  • women with a cytological prediction of pLSILPossible LSIL in the Australian Modified Bethesda System is broadly equivalent to ASCUS in US Bethesda system./LSILLow-grade squamous intraepithelial lesionThe low-grade squamous intraepithelial lesion (LSIL) category is the morphological correlate of productive viral infection. It is to be used when the scientist/pathologist observes changes that would have been described as ‘HPV effect’ or ‘CIN 1’ in the previous Australian terminology and represents part of the previous ‘low-grade squamous epithelial abnormality’ category. and a positive oncogenic HPV (not 16/18)Women with a positive HPV test result of other oncogenic HPV types other than types 16 and 18 detected using routine HPV testing in a pathology laboratory. test result.
N/A
Modelling study findings

For women with a positive oncogenic HPV (not 16/18)Women with a positive HPV test result of other oncogenic HPV types other than types 16 and 18 detected using routine HPV testing in a pathology laboratory. test result and reflex LBCLiquid based cytology(LBC) is a way of preparing cervical samples for examination in the laboratory. prediction of pLSILPossible LSIL in the Australian Modified Bethesda System is broadly equivalent to ASCUS in US Bethesda system./LSILLow-grade squamous intraepithelial lesionThe low-grade squamous intraepithelial lesion (LSIL) category is the morphological correlate of productive viral infection. It is to be used when the scientist/pathologist observes changes that would have been described as ‘HPV effect’ or ‘CIN 1’ in the previous Australian terminology and represents part of the previous ‘low-grade squamous epithelial abnormality’ category.:

  • modelling comparing 12-month follow-up with immediate colposcopy predicted that the 20-year risk of developing invasive cervical cancer for those who have 12-month follow-up surveillance is lower than the risk in women with a screening cytology result of LSILLow-grade squamous intraepithelial lesionThe low-grade squamous intraepithelial lesion (LSIL) category is the morphological correlate of productive viral infection. It is to be used when the scientist/pathologist observes changes that would have been described as ‘HPV effect’ or ‘CIN 1’ in the previous Australian terminology and represents part of the previous ‘low-grade squamous epithelial abnormality’ category. in the pre-renewal NCSPNational Cervical Screening ProgramA joint program of the Australian, state and territory governments. It aims to reduce morbidity and mortality from cervical cancer, in a cost-effective manner through an organised approach to cervical screening. The program encourages women in the target population to have regular Pap smears. (i.e. lower than the accepted benchmark risk for 12-month follow-up in Australia).
  • performing both 12-month and 24-month follow-up results in <1% difference in cervical cancer incidence and mortality and <1% difference in colposcopies, compared with 12-month follow-up only.
N/A
Based on data for first 2 years of the renewed NCSPNational Cervical Screening ProgramA joint program of the Australian, state and territory governments. It aims to reduce morbidity and mortality from cervical cancer, in a cost-effective manner through an organised approach to cervical screening. The program encourages women in the target population to have regular Pap smears., risks are low for women at intermediate risk whose follow-up test is HPV (not 16/18) and LBCLiquid based cytology(LBC) is a way of preparing cervical samples for examination in the laboratory. prediction negative, pLSILPossible LSIL in the Australian Modified Bethesda System is broadly equivalent to ASCUS in US Bethesda system. or LSILLow-grade squamous intraepithelial lesionThe low-grade squamous intraepithelial lesion (LSIL) category is the morphological correlate of productive viral infection. It is to be used when the scientist/pathologist observes changes that would have been described as ‘HPV effect’ or ‘CIN 1’ in the previous Australian terminology and represents part of the previous ‘low-grade squamous epithelial abnormality’ category.:
  • The likelihood of histologically confirmed CIN2+ is approximately 8.1–8.5%.
  • The likelihood of histologically confirmed CIN3+ is approximately 3.1–3.4%.
  • The risk of invasive cervical cancer is extremely low (0.02%).

Ranges reflect variation depending on whether or not histological outcomes are restricted to occurring within 6 months of referral.

N/A [2]

*Note that grading of the evidence was performed according the NHMRCNational Health and Medical Research Council guidelines in place at the time of the original development of these guidelines (for consistency).
**2020 review of NCSPNational Cervical Screening ProgramA joint program of the Australian, state and territory governments. It aims to reduce morbidity and mortality from cervical cancer, in a cost-effective manner through an organised approach to cervical screening. The program encourages women in the target population to have regular Pap smears. data.

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Recommendations

Flowchart 6.1. Cervical screening pathway for primary oncogenic HPV testing (Note: this updated management flowchart comes into effect on 1 February 2020)

Flowchart 6 1 updated.jpg

Evidence-based recommendationQuestion mark transparent.png Grade
REC6.6: Positive oncogenic HPV (not 16/18)Women with a positive HPV test result of other oncogenic HPV types not including types 16 and 18 detected using routine HPV testing in a pathology laboratory. test result at routine screening

Women with a positive oncogenic HPV (not 16/18)Women with a positive HPV test result of other oncogenic HPV types other than types 16 and 18 detected using routine HPV testing in a pathology laboratory. test result, with a LBCLiquid based cytology(LBC) is a way of preparing cervical samples for examination in the laboratory. report of negative or prediction of pLSILPossible LSIL in the Australian Modified Bethesda System is broadly equivalent to ASCUS in US Bethesda system./LSILLow-grade squamous intraepithelial lesionThe low-grade squamous intraepithelial lesion (LSIL) category is the morphological correlate of productive viral infection. It is to be used when the scientist/pathologist observes changes that would have been described as ‘HPV effect’ or ‘CIN 1’ in the previous Australian terminology and represents part of the previous ‘low-grade squamous epithelial abnormality’ category., should have a repeat HPV test in 12 months.

C
Practice pointQuestion mark transparent.png

REC6.7: Referral of women with a positive oncogenic HPV (not 16/18)Women with a positive HPV test result of other oncogenic HPV types other than types 16 and 18 detected using routine HPV testing in a pathology laboratory. test result and LBCLiquid based cytology(LBC) is a way of preparing cervical samples for examination in the laboratory. prediction of pHSILPossible HSIL in the Australian Modified Bethesda System is broadly equivalent to ASC-H in US Bethesda system., HSILHigh-grade squamous intraepithelial lesionIn the Australian context, HSIL is used to refer to a cytology predictive of a high grade precancerous lesion (AMBS 2004), or histologically confirmed high grade precancerous lesion (HSIL-CIN2 or HSIL-CIN3 as per LAST terminology). or any glandular abnormality
Women with a positive oncogenic HPV (not 16/18)Women with a positive HPV test result of other oncogenic HPV types other than types 16 and 18 detected using routine HPV testing in a pathology laboratory. test result, with a LBCLiquid based cytology(LBC) is a way of preparing cervical samples for examination in the laboratory. prediction of pHSILPossible HSIL in the Australian Modified Bethesda System is broadly equivalent to ASC-H in US Bethesda system./HSILHigh-grade squamous intraepithelial lesionIn the Australian context, HSIL is used to refer to a cytology predictive of a high grade precancerous lesion (AMBS 2004), or histologically confirmed high grade precancerous lesion (HSIL-CIN2 or HSIL-CIN3 as per LAST terminology). or any glandular abnormality, should be referred for colposcopic assessment at the earliest opportunity, ideally within 8 weeks.

Consensus-based recommendation*Question mark transparent.png

REC6.8: Referral to gynaecological oncologist for LBCLiquid based cytology(LBC) is a way of preparing cervical samples for examination in the laboratory. prediction of invasive disease
Women who have a positive oncogenic HPV (not 16/18)Women with a positive HPV test result of other oncogenic HPV types other than types 16 and 18 detected using routine HPV testing in a pathology laboratory. test result with a LBCLiquid based cytology(LBC) is a way of preparing cervical samples for examination in the laboratory. report of invasive cancer (squamous, glandular or other) should be referred to a gynaecological oncologist or gynaecological cancer centre for urgent evaluation, ideally within 2 weeks.

Evidence-based recommendationQuestion mark transparent.png Grade
REC6.9: Management after follow-up HPV test at 12 months, following initial positive oncogenic HPV (not 16/18)Women with a positive HPV test result of other oncogenic HPV types other than types 16 and 18 detected using routine HPV testing in a pathology laboratory. test result

At follow-up HPV testing 12 months after a positive oncogenic HPV (not 16/18)Women with a positive HPV test result of other oncogenic HPV types other than types 16 and 18 detected using routine HPV testing in a pathology laboratory. test result with reflex LBCLiquid based cytology(LBC) is a way of preparing cervical samples for examination in the laboratory. negative or pLSILPossible LSIL in the Australian Modified Bethesda System is broadly equivalent to ASCUS in US Bethesda system./LSILLow-grade squamous intraepithelial lesionThe low-grade squamous intraepithelial lesion (LSIL) category is the morphological correlate of productive viral infection. It is to be used when the scientist/pathologist observes changes that would have been described as ‘HPV effect’ or ‘CIN 1’ in the previous Australian terminology and represents part of the previous ‘low-grade squamous epithelial abnormality’ category.:

  • if a woman has a positive oncogenic HPV (16/18)Women with a positive HPV test result of HPV types 16 and/or 18 detected using routine HPV testing in a pathology laboratory. test result, reflex LBCLiquid based cytology(LBC) is a way of preparing cervical samples for examination in the laboratory. will be performed and she should be referred for colposcopic assessment
  • if a woman has a positive oncogenic HPV (not 16/18)Women with a positive HPV test result of other oncogenic HPV types other than types 16 and 18 detected using routine HPV testing in a pathology laboratory. test result, with a reflex LBCLiquid based cytology(LBC) is a way of preparing cervical samples for examination in the laboratory. report of pHSILPossible HSIL in the Australian Modified Bethesda System is broadly equivalent to ASC-H in US Bethesda system./HSILHigh-grade squamous intraepithelial lesionIn the Australian context, HSIL is used to refer to a cytology predictive of a high grade precancerous lesion (AMBS 2004), or histologically confirmed high grade precancerous lesion (HSIL-CIN2 or HSIL-CIN3 as per LAST terminology). or any glandular abnormality, she should be referred for colposcopic assessment at the earliest opportunity, ideally within 8 weeks
  • if oncogenic HPV is not detected, the woman should be advised to return to routine 5-yearly screening.


Approval: 1-Feb-2021 – 31-Jan-2026

C
Consensus-based recommendationQuestion mark transparent.png

REC6.10: Management after follow-up HPV test at 12 months, after initial positive oncogenic HPV (not 16/18)Women with a positive HPV test result of other oncogenic HPV types other than types 16 and 18 detected using routine HPV testing in a pathology laboratory. test result
At follow-up HPV testing 12 months after a positive oncogenic HPV (not 16/18)Women with a positive HPV test result of other oncogenic HPV types other than types 16 and 18 detected using routine HPV testing in a pathology laboratory. test result with reflex LBCLiquid based cytology(LBC) is a way of preparing cervical samples for examination in the laboratory. negative or pLSILPossible LSIL in the Australian Modified Bethesda System is broadly equivalent to ASCUS in US Bethesda system./LSILLow-grade squamous intraepithelial lesionThe low-grade squamous intraepithelial lesion (LSIL) category is the morphological correlate of productive viral infection. It is to be used when the scientist/pathologist observes changes that would have been described as ‘HPV effect’ or ‘CIN 1’ in the previous Australian terminology and represents part of the previous ‘low-grade squamous epithelial abnormality’ category.:

  • if a woman has a positive oncogenic HPV (not 16/18)Women with a positive HPV test result of other oncogenic HPV types other than types 16 and 18 detected using routine HPV testing in a pathology laboratory. test result, with a reflex LBCLiquid based cytology(LBC) is a way of preparing cervical samples for examination in the laboratory. report of negative or prediction of pLSILPossible LSIL in the Australian Modified Bethesda System is broadly equivalent to ASCUS in US Bethesda system./LSILLow-grade squamous intraepithelial lesionThe low-grade squamous intraepithelial lesion (LSIL) category is the morphological correlate of productive viral infection. It is to be used when the scientist/pathologist observes changes that would have been described as ‘HPV effect’ or ‘CIN 1’ in the previous Australian terminology and represents part of the previous ‘low-grade squamous epithelial abnormality’ category., and does not fall into any of the categories in REC6.11, she should have a further follow-up HPV test in a further 12 months.


Approval: 1-Feb-2021

Practice pointQuestion mark transparent.png

REC6.11: Management after follow-up HPV test at 12 months, following initial positive oncogenic HPV (not 16/18)Women with a positive HPV test result of other oncogenic HPV types other than types 16 and 18 detected using routine HPV testing in a pathology laboratory. test result, for women who:

  • were overdue for screening by at least 2 years prior to their initial positive oncogenic HPV (not 16/18)Women with a positive HPV test result of other oncogenic HPV types other than types 16 and 18 detected using routine HPV testing in a pathology laboratory. test result
  • identify as being of Aboriginal or Torres Strait Islander descent
  • age 50 years or older.


At follow-up HPV testing 12 months after a positive oncogenic HPV (not 16/18)Women with a positive HPV test result of other oncogenic HPV types other than types 16 and 18 detected using routine HPV testing in a pathology laboratory. test result with reflex LBCLiquid based cytology(LBC) is a way of preparing cervical samples for examination in the laboratory. negative or pLSILPossible LSIL in the Australian Modified Bethesda System is broadly equivalent to ASCUS in US Bethesda system./LSILLow-grade squamous intraepithelial lesionThe low-grade squamous intraepithelial lesion (LSIL) category is the morphological correlate of productive viral infection. It is to be used when the scientist/pathologist observes changes that would have been described as ‘HPV effect’ or ‘CIN 1’ in the previous Australian terminology and represents part of the previous ‘low-grade squamous epithelial abnormality’ category.:

  • if a woman has a positive oncogenic HPV (any type)Women with a positive HPV test result of any oncogenic HPV types detected using routine HPV testing in a pathology laboratory. test result, she should be referred for colposcopic assessment.


Approval: 1-Feb-2021

Consensus-based recommendationQuestion mark transparent.png

REC6.12: Management after second follow-up HPV test, following initial positive oncogenic HPV (not 16/18)Women with a positive HPV test result of other oncogenic HPV types other than types 16 and 18 detected using routine HPV testing in a pathology laboratory. test result
At follow-up HPV testing 12 months after a first follow-up positive oncogenic HPV (not 16/18)Women with a positive HPV test result of other oncogenic HPV types other than types 16 and 18 detected using routine HPV testing in a pathology laboratory. test result with reflex LBCLiquid based cytology(LBC) is a way of preparing cervical samples for examination in the laboratory. negative or pLSILPossible LSIL in the Australian Modified Bethesda System is broadly equivalent to ASCUS in US Bethesda system./LSILLow-grade squamous intraepithelial lesionThe low-grade squamous intraepithelial lesion (LSIL) category is the morphological correlate of productive viral infection. It is to be used when the scientist/pathologist observes changes that would have been described as ‘HPV effect’ or ‘CIN 1’ in the previous Australian terminology and represents part of the previous ‘low-grade squamous epithelial abnormality’ category.:

  • if a woman has a positive oncogenic HPV (any type)Women with a positive HPV test result of any oncogenic HPV types detected using routine HPV testing in a pathology laboratory. test result, reflex LBCLiquid based cytology(LBC) is a way of preparing cervical samples for examination in the laboratory. will be performed and she should be referred for colposcopic assessment
  • if oncogenic HPV is not detected, the woman should be advised to return to routine 5-yearly screening.


Approval: 1-Feb-2021


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Benefits and harms

While all screening programs will fail to detect some cases, implementation of these recommendations does not present any significant concern about the potential for missed cancers. Rates of cervical cancer are low in Australia, compared with international rates.[16] Modelling, taking into account post-colposcopy management as recommended in these guidelines, has predicted that a 31–36% reduction in incidence and mortality may be achievable in unvaccinated cohorts and a 24–29% reduction may be achievable in cohorts offered vaccination (Section 2. The rationale for primary HPV screening and Section 5. Benefits, harms and cost-effectiveness of cervical screening in the renewed NCSP).[17]

In 2005, the NCSPNational Cervical Screening ProgramA joint program of the Australian, state and territory governments. It aims to reduce morbidity and mortality from cervical cancer, in a cost-effective manner through an organised approach to cervical screening. The program encourages women in the target population to have regular Pap smears. adopted a policy of 12-month follow-up for women with a cytological prediction of pLSILPossible LSIL in the Australian Modified Bethesda System is broadly equivalent to ASCUS in US Bethesda system./LSILLow-grade squamous intraepithelial lesionThe low-grade squamous intraepithelial lesion (LSIL) category is the morphological correlate of productive viral infection. It is to be used when the scientist/pathologist observes changes that would have been described as ‘HPV effect’ or ‘CIN 1’ in the previous Australian terminology and represents part of the previous ‘low-grade squamous epithelial abnormality’ category., replacing the previous policy of immediate referral to colposcopy. A recent evaluation by the NCSPNational Cervical Screening ProgramA joint program of the Australian, state and territory governments. It aims to reduce morbidity and mortality from cervical cancer, in a cost-effective manner through an organised approach to cervical screening. The program encourages women in the target population to have regular Pap smears. Quality and Safety Monitoring Committee found that this policy was not associated with an increase in the incidence of cervical cancer in women age 20–69 years.[18]

Within the renewed NCSPNational Cervical Screening ProgramA joint program of the Australian, state and territory governments. It aims to reduce morbidity and mortality from cervical cancer, in a cost-effective manner through an organised approach to cervical screening. The program encourages women in the target population to have regular Pap smears., the policy of 12-month follow-up for women with a LBCLiquid based cytology(LBC) is a way of preparing cervical samples for examination in the laboratory. prediction of pLSILPossible LSIL in the Australian Modified Bethesda System is broadly equivalent to ASCUS in US Bethesda system./LSILLow-grade squamous intraepithelial lesionThe low-grade squamous intraepithelial lesion (LSIL) category is the morphological correlate of productive viral infection. It is to be used when the scientist/pathologist observes changes that would have been described as ‘HPV effect’ or ‘CIN 1’ in the previous Australian terminology and represents part of the previous ‘low-grade squamous epithelial abnormality’ category. would apply only to the subgroup of women at intermediate risk of significant cervical abnormality based on HPV testing with partial genotyping, in contrast to the pre-renewal program in which the policy applies to an undifferentiated group of women with either high or intermediate risk. Accordingly, modelled results suggest that the risk for women with a positive oncogenic HPV (not 16/18)Women with a positive HPV test result of other oncogenic HPV types other than types 16 and 18 detected using routine HPV testing in a pathology laboratory. test result and a reflex LBCLiquid based cytology(LBC) is a way of preparing cervical samples for examination in the laboratory. prediction of pLSILPossible LSIL in the Australian Modified Bethesda System is broadly equivalent to ASCUS in US Bethesda system./LSILLow-grade squamous intraepithelial lesionThe low-grade squamous intraepithelial lesion (LSIL) category is the morphological correlate of productive viral infection. It is to be used when the scientist/pathologist observes changes that would have been described as ‘HPV effect’ or ‘CIN 1’ in the previous Australian terminology and represents part of the previous ‘low-grade squamous epithelial abnormality’ category. who have 12-month follow-up surveillance, is lower than the risk in women with a screening cytological prediction of LSILLow-grade squamous intraepithelial lesionThe low-grade squamous intraepithelial lesion (LSIL) category is the morphological correlate of productive viral infection. It is to be used when the scientist/pathologist observes changes that would have been described as ‘HPV effect’ or ‘CIN 1’ in the previous Australian terminology and represents part of the previous ‘low-grade squamous epithelial abnormality’ category. in the pre-renewal NCSPNational Cervical Screening ProgramA joint program of the Australian, state and territory governments. It aims to reduce morbidity and mortality from cervical cancer, in a cost-effective manner through an organised approach to cervical screening. The program encourages women in the target population to have regular Pap smears. (i.e. the risk in this group is lower than the accepted benchmark risk for 12-month follow-up in Australia).

More than half of women with an oncogenic HPV infection are expected to clear the infection within 12 months.[19] Those with persistent infection (or with an HPV infection detected on repeat testing) would be identified at the 12-month HPV repeat test.

The original prediction of low risk among women with oncogenic HPV (not 16/18) and a reflex LBCLiquid based cytology(LBC) is a way of preparing cervical samples for examination in the laboratory. prediction of pLSILPossible LSIL in the Australian Modified Bethesda System is broadly equivalent to ASCUS in US Bethesda system./LSILLow-grade squamous intraepithelial lesionThe low-grade squamous intraepithelial lesion (LSIL) category is the morphological correlate of productive viral infection. It is to be used when the scientist/pathologist observes changes that would have been described as ‘HPV effect’ or ‘CIN 1’ in the previous Australian terminology and represents part of the previous ‘low-grade squamous epithelial abnormality’ category. has been borne out by a 2020 review of NCSPNational Cervical Screening ProgramA joint program of the Australian, state and territory governments. It aims to reduce morbidity and mortality from cervical cancer, in a cost-effective manner through an organised approach to cervical screening. The program encourages women in the target population to have regular Pap smears. data from the first 2 years of the renewed program. In fact, the risk of CIN2+ among women presenting for colposcopy following persistent detection of HPV (not 16/18), in the absence of pHSILPossible HSIL in the Australian Modified Bethesda System is broadly equivalent to ASC-H in US Bethesda system., HSILHigh-grade squamous intraepithelial lesionIn the Australian context, HSIL is used to refer to a cytology predictive of a high grade precancerous lesion (AMBS 2004), or histologically confirmed high grade precancerous lesion (HSIL-CIN2 or HSIL-CIN3 as per LAST terminology)., cancer of glandular abnormality on cytology, is low enough to justify a further 12 months of surveillance prior to referral to colposcopy. This change results in a better balance of benefits and potential harms by allowing women at very low risk of CIN2+ (and based on current data, very low risk of cancer) a further 12 months, by which time many women will have cleared the HPV infection and will then not require colposcopy at all.

Implementation of these recommendations will avoid many unnecessary colposcopies and associated harms (including biopsy, overtreatment, anxiety and financial costs) for women with HPV-related cervical abnormalities that would resolve spontaneously without medical intervention.

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Health system implications of these recommendations

Clinical practice

Colposcopic assessment and management will be more challenging in the renewed NCSPNational Cervical Screening ProgramA joint program of the Australian, state and territory governments. It aims to reduce morbidity and mortality from cervical cancer, in a cost-effective manner through an organised approach to cervical screening. The program encourages women in the target population to have regular Pap smears. because there will be a higher proportion of women with a positive oncogenic HPV test result who have minimal or no cytological changes. Women with persistent infections with oncogenic HPV (not 16/18) will be referred to colposcopy after 12 months and a very large proportion of these will represent productive HPV infection without neoplastic potential.

This has been borne out in practice in the first 2 years of the renewed NCSPNational Cervical Screening ProgramA joint program of the Australian, state and territory governments. It aims to reduce morbidity and mortality from cervical cancer, in a cost-effective manner through an organised approach to cervical screening. The program encourages women in the target population to have regular Pap smears., placing considerable pressure on colposcopy services, with some women in this category therefore facing considerable delay in accessing colposcopy. The change, implemented in 2020, to allow a further 12 months of surveillance prior to referral to colposcopy is designed to safely relieve these pressures.

Resourcing

Updated modelling, taking into account these detailed guideline recommendations, and taking into account the reduction in HPV 16/18Only HPV types 16 and or 18 detected using routine HPV screening tests in laboratory. infections due to vaccination in the population, has informed an assessment of the resourcing associated with partial genotyping strategies (see Section 5. Benefits, harms and cost-effectiveness of cervical screening in the renewed NCSP).

Barriers to implementation

Healthcare professionals may be reluctant to delay colposcopy in women who have a positive oncogenic HPV (not 16/18)Women with a positive HPV test result of other oncogenic HPV types other than types 16 and 18 detected using routine HPV testing in a pathology laboratory. test result, despite this being their current practice with low-grade cytology. Education of GPs and other healthcare professionals who provide cervical screening services, emphasising the safety of this approach, will be essential to the implementation of this recommendation.

Some women may be reluctant to accept a 12-month delay in referral for colposcopy, especially if they are aware of their HPV test result. Education of women and careful explanation by their healthcare provider will be of paramount importance.

GPs, other healthcare professionals and women participating in screening should understand that the recommendation to defer colposcopy (if needed at all) for 12 months is unchanged from accepted practice for women with an abnormal Pap test result predicting pLSILPossible LSIL in the Australian Modified Bethesda System is broadly equivalent to ASCUS in US Bethesda system./LSILLow-grade squamous intraepithelial lesionThe low-grade squamous intraepithelial lesion (LSIL) category is the morphological correlate of productive viral infection. It is to be used when the scientist/pathologist observes changes that would have been described as ‘HPV effect’ or ‘CIN 1’ in the previous Australian terminology and represents part of the previous ‘low-grade squamous epithelial abnormality’ category..

Conversely, GPs may not refer women with a persistent positive oncogenic HPV (not 16/18)Women with a positive HPV test result of other oncogenic HPV types other than types 16 and 18 detected using routine HPV testing in a pathology laboratory. test result to colposcopy, but this risk will be mitigated by the laboratory report to the GP clearly recommending referral, and by existing registry follow-up with reminder letters as needed.

Similarly, the women in this situation may not fully understand the need for colposcopy, especially if the reflex LBCLiquid based cytology(LBC) is a way of preparing cervical samples for examination in the laboratory. result is negative, and may fail to attend. Patient education and registry reminder letters will play an important role in this situation.

Effective communication with health professionals, and with affected women, will be necessary to implement the change in the pathway for women with HPV (not 16/18) detected and negative, pLSILPossible LSIL in the Australian Modified Bethesda System is broadly equivalent to ASCUS in US Bethesda system. or LSILLow-grade squamous intraepithelial lesionThe low-grade squamous intraepithelial lesion (LSIL) category is the morphological correlate of productive viral infection. It is to be used when the scientist/pathologist observes changes that would have been described as ‘HPV effect’ or ‘CIN 1’ in the previous Australian terminology and represents part of the previous ‘low-grade squamous epithelial abnormality’ category. cytology (Flowchart 6.1).

ColposcopyThe examination of the cervix and vagina with a magnifying instrument called a colposcope, to check for abnormalities. waiting lists will need to be re-prioritised and primary health providers may find that women previously referred to colposcopy are returned to primary care for a further follow-up HPV test. This will require careful communication. Laboratories will need to rework their procedures for reporting recommended management in these cases and for many laboratories a software adjustment will be needed, where decision support software is in place. The NCSRNational Cancer Screening Register will also need to adjust its follow-up communications accordingly.

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Appendices

Jutta's magnifying glass icon.pngPICO questions 1a & 1b View Systematic review report q 1aView Systematic review report q 1a View Systematic review report q 1bView Systematic review report q 1b View Evidence Statement q 1aView Evidence Statement q 1a
View Evidence Statement q 1bView Evidence Statement q 1b View Modelling report q 1a&1bView Modelling report q 1a

References

  1. 1.01.1 Medical Services Advisory Committee. MSAC Outcomes. Application No. 1276 – Renewal of the National Cervical Screening Program. [homepage on the internet] Canberra: Australian Government Department of Health; 2014 [updated 2015 Apr]. Available from: http://www.msac.gov.au/internet/msac/publishing.nsf/Content/FD36D6990FFAA639CA25799200058940/$File/1276%20-%20Final%20MSAC%20PSD%20-%20NCSP%20Renewal.pdf.
  2. 2.02.12.22.32.42.52.62.7 National Cervical Screening Program (NCSPNational Cervical Screening ProgramA joint program of the Australian, state and territory governments. It aims to reduce morbidity and mortality from cervical cancer, in a cost-effective manner through an organised approach to cervical screening. The program encourages women in the target population to have regular Pap smears.). National Cancer Screening Register (NCSR) [unpublished data]. Department of Health, Australian Commonwealth Government; 2020 Apr 16. Report No.: [Search period: 1 December 2017 to 31 December 2019].
  3. 3.03.1 National Health and Medical Research Council. Screening to prevent cervical cancer: guidelines for the management of asymptomatic women with screen detected abnormalities. Canberra: NHMRCNational Health and Medical Research Council; 2005.
  4. 4.04.14.2 Gage JC, Schiffman M, Solomon D, Wheeler CM, Gravitt PE, Castle PE, et al. Risk of precancer determined by HPV genotype combinations in women with minor cytologic abnormalities. Cancer Epidemiol Biomarkers Prev 2013 Jun;22(6):1095-101 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/23603204.
  5. 5.05.15.2 Castle PE, Glass AG, Rush BB, Scott DR, Wentzensen N, Gage JC, et al. Clinical human papillomavirus detection forecasts cervical cancer risk in women over 18 years of follow-up. J Clin Oncol 2012 Sep 1;30(25):3044-50 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/22851570.
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  9. 9.09.1 Stoler MH, Wright TC Jr, Sharma A, Apple R, Gutekunst K, Wright TL, et al. High-risk human papillomavirus testing in women with ASC-US cytology: results from the ATHENA HPV study. Am J Clin Pathol 2011 Mar;135(3):468-75 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/21350104.
  10. 10.010.1 Wright TC Jr, Stoler MH, Sharma A, Zhang G, Behrens C, Wright TL, et al. Evaluation of HPV-16 and HPV-18 genotyping for the triage of women with high-risk HPV+ cytology-negative results. Am J Clin Pathol 2011 Oct;136(4):578-86 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/21917680.
  11. Einstein MH, Martens MG, Garcia FA, Ferris DG, Mitchell AL, Day SP, et al. Clinical validation of the Cervista HPV HR and 16/18 genotyping tests for use in women with ASC-US cytology. Gynecol Oncol 2010 Aug 1;118(2):116-22 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/20488510.
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  17. Lew JB, Simms K, Smith M, et al. National Cervical Screening Program renewal: effectiveness modelling and economic evaluation in the Australian setting (Assessment report).MSAC Application No. 1276. Canberra: MSACThe Australian Medical Services Advisory Committee; 2014.
  18. Australian Institute of Health and Welfare. Report on monitoring activities of the National Cervical Screening Program Safety Monitoring Committee. Cancer series 80. Cat. no. CAN 77. Canberra: AIHWAustralian Institute of Health and Welfare; 2013 Available from: http://www.aihw.gov.au/publication-detail/?id=60129545158).
  19. Rodríguez AC, Schiffman M, Herrero R, Wacholder S, Hildesheim A, Castle PE, et al. Rapid clearance of human papillomavirus and implications for clinical focus on persistent infections. J Natl Cancer Inst 2008 Apr 2;100(7):513-7 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/18364507.

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