9. Management of histologically confirmed low-grade squamous abnormalities

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Background

According to the two-tiered nomenclature for cervical histology recommended by the Lower Anogenital Squamous Terminology (LASTLower Anogenital Squamous Terminology) Standardization Project[1] and adopted by the Royal College of Pathologists of Australasia, non-invasive human papillomavirus (HPVHuman papillomavirus)-associated squamous lesions are classified as follows (see Chapter 3. Terminology):

Current 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.) guidelines do not recommend treatment for histologically confirmed low-grade squamous intraepithelial lesions (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.); cervical intraepithelial neoplasia grade one (CIN1mild dysplasia) or a lesser lesion detected on biopsy. These lesions are considered to be an expression of a productive HPV infection.[2] The 2005 national guideline for the management of screen-detected cervical abnormalities[2] recommended that women with histologically confirmed low-grade squamous abnormalities undergo repeat conventional cytology (Pap test) at 12 and 24 months, and return to routine screening if both tests are negative or continue annual cytology until two consecutive tests are negative.

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., it is common for a woman’s cytology status to fluctuate between low-grade abnormality and negative,[2] probably due to HPV infection, clearance and reinfection.[2] Within programs based on primary HPV screening, clinical decisions can be informed by known HPV status as well as cytology.

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., the HPV status of individual women with histologically confirmed low-grade squamous abnormalities is not routinely available and recommendations are based on the assumption that it is unknown. Under 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., in contrast, the clinical significance of histological, colposcopic and cytological findings in women with screen-detected abnormalities is assessed in the context of known positive HPV status.

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Evidence

Systematic review evidence

A systematic review was performed to identify studies evaluating efficacy and safety outcomes of management options for women with a positive oncogenic HPV-test result, a colposcopic impression 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. and histologically confirmed CIN1mild dysplasia or less on biopsy, whether concordant or discordant with referral liquid-based cytology (LBCLiquid based cytology(LBC) is a way of preparing cervical samples for examination in the laboratory.):

  • For those with a cytology finding of negative, possible low-grade squamous epithelial lesion or low-grade squamous epithelial lesion (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.), repeat HPV test at 12 months was compared with the combination of repeat LBCLiquid based cytology(LBC) is a way of preparing cervical samples for examination in the laboratory. and HPV test (co-testingHPV test and LBC both requested and performed on a cervical sample.) at 12 months.
  • For those with a cytology finding of possible or high-grade squamous epithelial lesion (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).), diagnostic excision was compared with co-testingHPV test and LBC both requested and performed on a cervical sample. at 12 months.

No randomised or pseudorandomised controlled trials were identified that compared:

  • HPV testing alone with co-testingHPV test and LBC both requested and performed on a cervical sample. as follow-up for women with a positive HPV test result with a reflex LBCLiquid based cytology(LBC) is a way of preparing cervical samples for examination in the laboratory. finding of 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.
  • excisional treatment with follow-up by co-testingHPV test and LBC both requested and performed on a cervical sample. in women with a reflex cytology finding 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)..

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

General literature review evidence

In the absence of any direct evidence from the systematic review, a general review of the literature was performed to inform consensus-based recommendations. The review focused on the management of women with:

  • a positive oncogenic HPV test result
  • a colposcopic impression 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.
  • histologically confirmed CIN1mild dysplasia or less on biopsy
  • referral cytology 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. or 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)..

Several studies examined outcomes following histologically confirmed CIN1mild dysplasia or less on biopsy.[2][3][4][5][6][7][8][9] The most relevant findings are summarised below:

  • In a prospective cohort study using data from the Kaiser Permanente Northern California health system,[4] the crude rate of CIN3+ was 0.7% following a single negative follow-up smear, 0.2% following a single negative follow-up HPV test and 0.1% following a negative follow-up co-testHPV test and LBC both requested and performed on a cervical sample. in women with HPV-positiveWomen with a positive HPV test result of any oncogenic HPV types detected using HPV testing platforms in a pathology laboratory. ASC-USAtypical squamous cells, undetermined significance or any 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 less than CIN2 on colposcopy/biopsy over a maximum of 7 years of follow-up.
  • In a prospective cohort study (ASCUSAtypical squamous cells, undetermined significanceIn the previous versions of the US Bethesda System, a category of atypical squamous cells of undetermined significance: The nature of the abnormality is uncertain or unequivocal. Included lesions equivalent to both possible low-grade squamous intraepithelial lesion (pLSIL) and possible high-grade squamous intraepithelial lesion (pHSIL) in the Australian Modified Bethesda System. Later versions (including the current version) of the Bethesda System split this category into ASC-H and ASC-US.-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. Triage Study),[7] 45% of women with baseline ASCUSAtypical squamous cells, undetermined significanceIn the previous versions of the US Bethesda System, a category of atypical squamous cells of undetermined significance: The nature of the abnormality is uncertain or unequivocal. Included lesions equivalent to both possible low-grade squamous intraepithelial lesion (pLSIL) and possible high-grade squamous intraepithelial lesion (pHSIL) in the Australian Modified Bethesda System. Later versions (including the current version) of the Bethesda System split this category into ASC-H and ASC-US./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 less than CIN2 on colposcopy/biopsy, a follow-up finding of 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). and a positive HPV test, developed CIN3+ within 2-year follow-up. (In this cohort, ASCUSAtypical squamous cells, undetermined significanceIn the previous versions of the US Bethesda System, a category of atypical squamous cells of undetermined significance: The nature of the abnormality is uncertain or unequivocal. Included lesions equivalent to both possible low-grade squamous intraepithelial lesion (pLSIL) and possible high-grade squamous intraepithelial lesion (pHSIL) in the Australian Modified Bethesda System. Later versions (including the current version) of the Bethesda System split this category into ASC-H and ASC-US. may have included ASC–H.)
  • One retrospective cohort study[8] of women who underwent loop electrosurgical excision procedure (LEEPLoop electrical excision procedureLoop electrical excision procedure) after referral 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). reported histologically confirmed CIN3+ in 41% of those with normal histology on the initial biopsy and 64% of those with CIN1mild dysplasia at initial biopsy. However, HPV status was not known.

Overall, available evidence suggests the following conclusions:

  • For women with a positive oncogenic HPV test result, ASC-USAtypical squamous cells, undetermined significance and histologically confirmed CIN1mild dysplasia or a lower-grade lesion, the negative predictive value of HPV follow-up testing alone will be greater than that of cytology alone, but less than co-testingHPV test and LBC both requested and performed on a cervical sample..
  • For women with a positive oncogenic HPV test result and initial referral cytology 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 finding of 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). at follow-up cytology indicates a substantial risk of future CIN3+.
  • Diagnostic excision of the transformation zone (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.) appears to be the optimal approach for women with a positive oncogenic HPV test result, a referral 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)., a colposcopic impression 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., and histologically confirmed CIN1mild dysplasia or a lower-grade lesion, especially if 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). is confirmed on cytopathology review.[10] The PPVPositive predictive value is variable and depends on the referral cytology prediction. One study reported that, where referral cytology predicted a high-grade abnormality, then the PPVPositive predictive value for identifying 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). on biopsy was 73%. If the referral cytology was low grade, the PPVPositive predictive value was 48%, demonstrating a clear relationship between the PPVPositive predictive value of colposcopic impression to the referral cytology prediction.[11]

A summary of the literature considered can be found in the Technical report.

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Recommendations

When there is discordance between the LBCLiquid based cytology(LBC) is a way of preparing cervical samples for examination in the laboratory. report and histopathology, review of both cytology and histopathology should be carried out to inform management decisions.


Consensus-based recommendationQuestion mark transparent.png

REC9.1: HPV test 12 months after histologically confirmed 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. (Less than or equal to CIN1mild dysplasia)
Women who have a positive oncogenic HPV (any type) test result with a LBCLiquid based cytology(LBC) is a way of preparing cervical samples for examination in the laboratory. report of either 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., and histologically confirmed Less than or equal to CIN1mild dysplasia on biopsy, should have a repeat HPV test 12 months later:

  • If oncogenic HPV is not detected at the repeat HPV test, the woman should return to routine 5 yearly screening.
  • If the repeat test is positive for oncogenic HPV (not 16/18) and the LBCLiquid based cytology(LBC) is a way of preparing cervical samples for examination in the laboratory. report is 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., the woman should have a further repeat HPV test in 12 months.
  • If the second follow-up HPV test is negative the woman should return to routine 5-yearly screening.
  • If the second follow-up test is HPV positiveWomen with a positive HPV test result of any oncogenic HPV types detected using HPV testing platforms in a pathology laboratory., the woman should be referred for colposcopic assessment informed by reflex LBCLiquid based cytology(LBC) is a way of preparing cervical samples for examination in the laboratory..
  • If the repeat test is positive for oncogenic HPV (not 16/18) and the LBCLiquid based cytology(LBC) is a way of preparing cervical samples for examination in the laboratory. report is 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)., the woman should be referred for colposcopic assessment.
  • If the repeat test is positive for oncogenic HPV (16/18), the woman should be referred for colposcopic assessment informed by the reflex LBCLiquid based cytology(LBC) is a way of preparing cervical samples for examination in the laboratory..
Consensus-based recommendationQuestion mark transparent.png

REC9.2: 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. (Less than or equal to CIN1mild dysplasia) should not be treated
Women who have 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 with a LBCLiquid based cytology(LBC) is a way of preparing cervical samples for examination in the laboratory. report of 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., who have undergone colposcopy and have a histologically confirmed 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. (Less than or equal to CIN1mild dysplasia), should not be treated, because these lesions are considered to be an expression of a productive HPV infection.

Consensus-based recommendationQuestion mark transparent.png

REC9.3: Diagnostic excision when 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). confirmed on cytopathology review
Women who have a positive oncogenic HPV test result (any type) with a LBCLiquid based cytology(LBC) is a way of preparing cervical samples for examination in the laboratory. report of 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). (confirmed after cytopathology review), and who have undergone colposcopy and have a histologically confirmed 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. (Less than or equal to CIN1mild dysplasia), should be offered 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..

Consensus-based recommendationQuestion mark transparent.png

REC9.4: Option for observation following cytological prediction of pHSILPossible HSIL in the Australian Modified Bethesda System is broadly equivalent to ASC-H in US Bethesda system.
Women who have 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 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. (confirmed after cytopathology review), and who have undergone colposcopy and have a histologically confirmed 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. (Less than or equal to CIN1mild dysplasia), could be offered 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..
If the colposcopist considers a period of observation is preferable to treatment, or the woman with these findings wishes to defer diagnostic excision, she can be offered observation with a HPV test and colposcopy at 6–12 months:

  • If oncogenic HPV is not detected at the repeat test, the HPV test should be repeated again in 12 months.
  • If the second follow-up test is negative, the woman should return to routine 5-yearly screening.
  • If the 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 at the repeat test, her reflex LBCLiquid based cytology(LBC) is a way of preparing cervical samples for examination in the laboratory. report is 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., and her colposcopic impression is normal 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 HPV test should be repeated annually.
  • When oncogenic HPV is not detected at two consecutive annual tests, the woman can return to 5-yearly screening.
  • If the 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 at the repeat test, and her LBCLiquid based cytology(LBC) is a way of preparing cervical samples for examination in the laboratory. prediction is 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 have a 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..
Practice pointQuestion mark transparent.png

REC9.5: Criteria for observation following cytological prediction of pHSILPossible HSIL in the Australian Modified Bethesda System is broadly equivalent to ASC-H in US Bethesda system.
Women should not be offered observation unless the colposcopic assessment meets all the following conditions:

  • ColposcopyThe examination of the cervix and vagina with a magnifying instrument called a colposcope, to check for abnormalities. is adequate.
  • 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. is completely visualised (Type 1 or 2 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.^).
  • 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. (Less than or equal to CIN1mild dysplasia) has been confirmed on histopathological review.


^IFCPCThe International Federation of Cervical Pathology and Colposcopy: International Federation of Cervical Pathology and ColposcopyThe examination of the cervix and vagina with a magnifying instrument called a colposcope, to check for abnormalities. 2011

Flowchart 9.1. Histological 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. following colposcopy for LBCLiquid based cytology(LBC) is a way of preparing cervical samples for examination in the laboratory. prediction of 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).

Histo LSIL following colp LSIL prediction HSIL.png







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REC9.6: Cytology review essential when test results are discordant
For women who have 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 with a histologically confirmed 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. (Less than or equal to CIN1mild dysplasia) after 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)., both the cytology and the histopathology should be reviewed by a pathologist from at least one of the reporting laboratories, who should then convey the results of the review to the colposcopist in order to inform the management plan.

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Benefits and harms

Despite the recommendations contained 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. guidelines, many women have continued to have unnecessary treatment for 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. (Less than or equal to CIN1mild dysplasia). These guidelines reiterate the previous advice, and colposcopists are advised not to treat these women unless there are exceptional circumstances. Compliance with these recommendations will benefit women by avoiding unnecessary treatment and consequent harms.

Cytological review for discordant results, as recommended in these guidelines, will benefit women by preventing over investigation and unnecessary treatment (see Chapter 5. Benefits, harms and cost-effectiveness of cervical screening in the renewed National Cervical Screening Program (NCSP)).

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Health system implications of these recommendations

Clinical practice

These recommendations represent minimal change to those that apply to 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]

Timely expert review of cytology and histology is recommended for women with low-grade histology results that are discordant with preceding high-grade cytology findings, before proceeding to any diagnostic treatment. Implementation of this recommendation may increase the workload of pathologists, laboratories and colposcopists. Clinicians may need to spend extra time reviewing results and providing advice to women.

The major change in clinical practice is that conventional cytology is replaced by HPV testing and reflex LBCLiquid based cytology(LBC) is a way of preparing cervical samples for examination in the laboratory. for the follow-up of women with histologically confirmed 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. (Less than or equal to CIN1mild dysplasia). The high negative predictive value of HPV testing should allow a significant proportion of women to return to routine cervical screening earlier than was possible under 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..

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Resourcing

Pathology review of discordant results may increase the workload of pathology services, leading to delay in service provision and increased distress to already anxious women. Ensuring that pathology services are adequately staffed (have enough pathologists and laboratory staff) may have cost implications.

Failure of colposcopists to comply with the recommendation not to offer treatment 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. (Less than or equal to CIN1mild dysplasia) would lead to unnecessary costs.

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Barriers to implementation

These recommendations represent minimal change to those that apply to 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] Accordingly, no significant barriers to implementation are anticipated. It is recommended that 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. (Less than or equal to CIN1mild dysplasia) should not be treated. Under 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., clinical practice has not fully complied with this recommendation. It is estimated that approximately 30% of 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. (Less than or equal to CIN1mild dysplasia) undergo excisional treatment. This decision may be due to physician or patient anxiety, especially when the finding is persistent. Under 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., colposcopists may continue to have concerns about conservative management of low-grade abnormalities, despite evidence supporting this approach. Failure to implement this recommendation would result in unnecessary treatment and consequent harms.

ColposcopistsHealth professionals, usually gynaecologists, trained to perform colposcopy. may proceed to diagnostic excisional procedures for apparent discordant pathology results, without arranging for expert pathology review to confirm the findings. Failure to implement the recommendation for cytological and histological review may lead to unnecessary treatment.

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Discussion

Unresolved issues

No unresolved issues have been identified.

The safety of this approach will be monitored by the Quality and Safety Monitoring Committee of 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..

Future research priorities

Prospective studies are needed to measure compliance with recommendations, especially the recommendation against routine treatment for histologically confirmed 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. (Less than or equal to CIN1mild dysplasia), and the recommendation for pathology review of discordant results.

Clinical trials are needed to determine the optimal management, and duration of observation, for persistent or fluctuating 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. (Less than or equal to CIN1mild dysplasia).

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References

  1. Darragh TM, Colgan TJ, Cox JT, Heller DS, Henry MR, Luff RD, et al. The Lower Anogenital Squamous Terminology Standardization Project for HPV-Associated Lesions: background and consensus recommendations from the College of American Pathologists and the American Society for Colposcopy and Cervical Pathology. Arch Pathol Lab Med 2012 Oct;136(10):1266-97 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/22742517.
  2. 2.02.12.22.32.42.52.6 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. Pacchiarotti A, Ferrari F, Bellardini P, Chini F, Collina G, Dalla Palma P, et al. Prognostic value of p16-INK4A protein in women with negative or CIN1 histology result: a follow-up study. Int J Cancer 2014 Feb 15;134(4):897-904 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/23913416.
  4. 4.04.1 Katki HA, Gage JC, Schiffman M, Castle PE, Fetterman B, Poitras NE, et al. Follow-up testing after colposcopy: five-year risk of CIN 2+ after a colposcopic diagnosis of CIN 1 or less. J Low Genit Tract Dis 2013 Apr;17(5 Suppl 1):S69-77 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/23519308.
  5. Matsumoto K, Hirai Y, Furuta R, Takatsuka N, Oki A, Yasugi T, et al. Subsequent risks for cervical precancer and cancer in women with low-grade squamous intraepithelial lesions unconfirmed by colposcopy-directed biopsy: results from a multicenter, prospective, cohort study. Int J Clin Oncol 2012 Jun;17(3):233-9 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/21748261.
  6. Castle PE, Gage JC, Wheeler CM, Schiffman M. The clinical meaning of a cervical intraepithelial neoplasia grade 1 biopsy. Obstet Gynecol 2011 Dec;118(6):1222-9 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/22105250.
  7. 7.07.1 Walker JL, Wang SS, Schiffman M, Solomon D, ASCUSAtypical squamous cells, undetermined significanceIn the previous versions of the US Bethesda System, a category of atypical squamous cells of undetermined significance: The nature of the abnormality is uncertain or unequivocal. Included lesions equivalent to both possible low-grade squamous intraepithelial lesion (pLSIL) and possible high-grade squamous intraepithelial lesion (pHSIL) in the Australian Modified Bethesda System. Later versions (including the current version) of the Bethesda System split this category into ASC-H and ASC-US. 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. Triage Study Group. Predicting absolute risk of CIN3 during post-colposcopic follow-up: results from the ASCUS-LSIL Triage Study (ALTS). Am J Obstet Gynecol 2006 Aug;195(2):341-8 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/16890545.
  8. 8.08.1 Lanneau GS, Skaggs V, Moore K, Stowell S, Zuna R, Gold MA. A LEEP cervical conization is rarely indicated for a two-step discrepancy. J Low Genit Tract Dis 2007 Jul;11(3):134-7 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/17596756.
  9. Pretorius RG, Peterson P, Azizi F, Burchette RJ. Subsequent risk and presentation of cervical intraepithelial neoplasia (CIN) 3 or cancer after a colposcopic diagnosis of CIN 1 or less. Am J Obstet Gynecol 2006 Nov;195(5):1260-5 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/17074547.
  10. Hopman EH, Kenemans P, Helmerhorst TJ. Positive predictive rate of colposcopic examination of the cervix uteri: an overview of literature. Obstet Gynecol Surv 1998 Feb;53(2):97-106 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/9487534.
  11. Bekkers RL, van de Nieuwenhof HP, Neesham DE, Hendriks JH, Tan J, Quinn MA. Does experience in colposcopy improve identification of high grade abnormalities? Eur J Obstet Gynecol Reprod Biol 2008 Nov;141(1):75-8 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/18760872.
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Appendices

Jutta's magnifying glass icon.pngPICO questions 4 View Systematic review report q 4View Systematic review report q 4 View General evidence summary table q 4View General evidence summary table q 4
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