Oncogenic HPV types not 16/18

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Women who have a positive oncogenic HPV 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 typesOncogenic HPV are HPV types considered capable of causing cancer. Types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59 and 68 are included in tests suitable for cervical screening. Some tests also detect type 66. 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 Chapter 3. Terminology).

Background

MSACThe Australian Medical Services Advisory Committee recommended 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 HPV oncogenic types 16/18).

HPV infections typically clear rapidly, with an estimated 67% of infections resolving by 12 months. 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 to allow for viral clearance.

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

  • Women with possible high-grade squamous intraepithelial lesions (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 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 Chapter 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 takes into account 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 Benefits, harms and cost-effectiveness of cervical screening in the renewed National Cervical Screening Program (NCSP) and Modelling reports.)

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Evidence

Systematic reviews and modelling studies were 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.

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.

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.

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 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..[2]
  • 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.[2]
  • 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[3][4] and four studies that reported results for outcomes on immediate colposcopy.[5][6][7][8][9][10][11][12][13] 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,[3] and in the other women were passively followed-up for a maximum of 18 years.[4]

Two studies[5][6][7][8][9][13] 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 aged > 18 years or > 30 years at baseline
  • after 18 years in a cohort aged > 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 aged > 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 aged >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 1

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 less than 1% difference in cervical cancer incidence and mortality and less than 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 aged 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.

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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 [3], [4]
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 with12-month follow-up only.
N/A
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Recommendations

Flowchart 6.1. Cervical screening pathway for primary oncogenic HPV testing

Cervical screening pathway.PNG
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 other than types 16 and 18 detected using routine HPV testing in a pathology laboratory.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 repeat 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 repeat 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, 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.
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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.[14] 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 (see Chapter 2. The rationale for primary HPV screening and (see Chapter 5. Benefits, harms and cost-effectiveness of cervical screening in the renewed National Cervical Screening Program (NCSP)).[15]

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 aged 20–69 years.[16]

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.[17] Those with persistent infection (or with an HPV infection detected on repeat testing) would be identified at the 12-month HPV repeat test and referred to colposcopy, regardless of LBCLiquid based cytology(LBC) is a way of preparing cervical samples for examination in the laboratory. result.

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. In particular, 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.

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 Chapter 5. Benefits, harms and cost-effectiveness of cervical screening in the renewed National Cervical Screening Program (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.

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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. 2.02.1 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.
  3. 3.03.13.2 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.
  4. 4.04.14.2 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.
  5. 5.05.1 Castle PE, Stoler MH, Wright TC Jr, Sharma A, Wright TL, Behrens CM. Performance of carcinogenic human papillomavirus (HPV) testing and HPV16 or HPV18 genotyping for cervical cancer screening of women aged 25 years and older: a subanalysis of the ATHENA study. Lancet Oncol 2011 Sep;12(9):880-90 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/21865084.
  6. 6.06.1 Cox JT, Castle PE, Behrens CM, Sharma A, Wright TC Jr, Cuzick J, et al. Comparison of cervical cancer screening strategies incorporating different combinations of cytology, HPV testing, and genotyping for HPV 16/18: results from the ATHENA HPV study. Am J Obstet Gynecol 2013 Mar;208(3):184.e1-184.e11 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/23174289.
  7. 7.07.1 Cuzick J, Thomas Cox J, Zhang G, Einstein MH, Stoler M, Trupin S, et al. Human papillomavirus testing for triage of women with low-grade squamous intraepithelial lesions. Int J Cancer 2013 Feb 15;132(4):959-66 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/22806936.
  8. 8.08.1 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.
  9. 9.09.1 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.
  10. 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.
  11. Einstein MH, Garcia FA, Mitchell AL, Day SP. Age-stratified performance of the Cervista HPV 16/18 genotyping test in women with ASC-US cytology. Cancer Epidemiol Biomarkers Prev 2011 Jun;20(6):1185-9 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/21527581.
  12. Castle PE, Eaton B, Reid J, Getman D, Dockter J. Comparison of human papillomavirus detection by Aptima HPV and cobas HPV tests in a population of women referred for colposcopy following detection of atypical squamous cells of undetermined significance by Pap cytology. J Clin Microbiol 2015 Apr;53(4):1277-81 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/25653409.
  13. 13.013.1 Mesher D, Szarewski A, Cadman L, Austin J, Ashdown-Barr L, Ho L, et al. Comparison of human papillomavirus testing strategies for triage of women referred with low-grade cytological abnormalities. Eur J Cancer 2013 Jun;49(9):2179-86 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/23452990.
  14. Australian Institute of Health and Welfare. Cervical screening in Australia 2012–2013. Cancer series no. 93. Cat. no. CAN 91. Canberra: AIHWAustralian Institute of Health and Welfare; 2015 Available from: http://www.aihw.gov.au/WorkArea/DownloadAsset.aspx?id=60129550872.
  15. 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.
  16. 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).
  17. 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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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
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