Discussion: Management of histologically confirmed high-grade squamous abnormalities

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Benefits and harms

The practice of treating all cases 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). (CIN2/3) has been highly effective and has led to a reduction in the risk of subsequent cervical cancer.

A very small number of women with 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). may be treated unnecessarily. However, it is not possible to identify these women in advance. This small risk must be weighed against the substantial evidence for the effectiveness of cervical screening and 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). (CIN2/3) treatment to prevent the development of invasive cervical cancer. The benefits of treating 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). (CIN2/3) outweigh the harms, and treating 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). (CIN2/3) is the basis for the documented success of the National Cervical Screening Program (NCSP).

See the 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

Recommendations regarding the management of women with 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). (CIN2/3) are consistent with present clinical practice.

Resourcing

No additional costs are anticipated.

Barriers to implementation

Women treated for 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). (CIN2/3) may choose not to attend for post-treatment co-testingHPV test and LBC both requested and performed on a cervical sample. as recommended. An Australian study using state registry data found that 53% of women treated for high-grade cervical dysplasia attended only a single HPV follow-up test.[1]

Some women will be very anxious if they have continuing abnormality (as may their GP) and a colposcopy may be needed for reassurance. However, treatment 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. (Less than or equal to CIN1mild dysplasia), even if persistent, should be avoided wherever possible.

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Discussion

Women who are undergoing Test of Cure, and who have 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 with any LBCLiquid based cytology(LBC) is a way of preparing cervical samples for examination in the laboratory. report, or 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). with any HPV test result, should be referred for colposcopy to exclude recurrent or residual disease. This more cautious post-treatment management of these women is warranted.

The National HPV Vaccination Program is expected to reduce the number of oncogenic HPV 16/18Only HPV types 16 and or 18 detected using routine HPV screening tests in laboratory. infections, high-grade abnormalities and the risk of cervical cancer directly in vaccinated women, as successive vaccinated cohorts mature and indirectly in unvaccinated women, via a reduction in the circulation of vaccine included HPV types within the population.

Unresolved issues

Although two negative co-tests are required before returning women to routine screening after treatment for 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). (CIN2/3), there is uncertainty regarding whether one negative co-testHPV test and LBC both requested and performed on a cervical sample. or a single negative HPV test would be sufficient before safely returning women to routine screening intervals of 5 years. This issue will be informed by the ongoing accumulation of national data by the Australian Institute of Health and Welfare (AIHWAustralian Institute of Health and Welfare) and will be considered by the Quality and Safety Monitoring Committee of the renewed NCSPNational Cervical Screening ProgramA joint program of the Australian, state and territory governments. It aims to reduce morbidity and mortality from cervical cancer, in a cost-effective manner through an organised approach to cervical screening. The program encourages women in the target population to have regular Pap smears..

For some women with a negative co-testHPV test and LBC both requested and performed on a cervical sample. result at 12 months but a positive HPV test and negative cytology result at 24 months, there is a possibility that the lesion is ‘cured’ and the positive oncogenic HPV test may indicate re-infection rather than recurrence. However, the scientific evidence to support this is currently not available.

Future research priorities

The role of p16 and ki67 in the triage 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). (CIN2), and its use 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., should be further investigated. Long-term follow-up studies of women with 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). (CIN2/3) cervical abnormalities that evaluate the clinical use of p16 and other molecular biomarkers, alone or in combination, are needed to guide the management of this group of women.

Outcomes of various post-treatment screening scenarios in longitudinal studies are needed to inform future recommendations for test of cure. These should compare the 5-year cumulative risk of subsequent 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). (CIN2+). Analysis by age groups (< 30 years and Greater than or equal to 30 years) would also be informative, as the specificity of HPV testing is lower in younger women.

The role of post-treatment HPV vaccination in unvaccinated women should be considered as a potential research activity.

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References

  1. Morrell S, Qian L. A whole-population profile of HPV testing as a test of cure for high-grade cervical dysplasia in NSW, Australia. J Med Screen 2014 Sep;21(3):151-62 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/24981084.
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