Follow-up after excisional treatment for AIS

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Background

Guidelines for 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.[1] recommended:

  • that decisions about management of histologically confirmed AISAdenocarcinoma in situ should take into account the woman’s age, fertility status, and excision margins
  • hysterectomy for women with histologically confirmed AISAdenocarcinoma in situ who have completed childbearing
  • that hysterectomy should not be undertaken as a treatment for AISAdenocarcinoma in situ without first performing a cone biopsy to exclude invasive carcinoma
  • that women with histologically confirmed invasive adenocarcinoma on cone or punch biopsy should be referred to a gynaecological oncologist or a gynaecological oncology unit.[1]

For women who wish to maintain fertility and choose cytological surveillance rather than hysterectomy, the risk of recurrent AISAdenocarcinoma in situ has been estimated at less than 10% and there is a very small risk of invasive adenocarcinoma, even when excision margins are negative.[2]
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Evidence

Systematic review evidence

A systematic review was undertaken to assess the safety and effectiveness of different follow-up options for women with AISAdenocarcinoma in situ after an excisional procedure (cone excision or LEEPLoop electrical excision procedureLoop electrical excision procedure) with complete excision confirmed histologically:

  • completion hysterectomy
  • repeat co-testingHPV test and LBC both requested and performed on a cervical sample. at 12 and 24 months after excision, returning to routine screening if both tests are negative at both follow-up points
  • annual cytology only.

The systematic literature search identified no relevant randomised or pseudorandomised controlled trials comparing different follow-up options for women who have undergone an excisional procedure for AISAdenocarcinoma in situ. The search strategies and inclusion and exclusion criteria used are described 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 on the follow-up of women who have undergone excisional treatment for AISAdenocarcinoma in situ to inform the drafting of relevant consensus-based recommendations.

Two prospective cohort studies[3][4] reported cancer outcomes for women with histologically confirmed AISAdenocarcinoma in situ managed conservatively after excisional biopsy.

For women diagnosed with AISAdenocarcinoma in situ on cone biopsy (almost 50% with involved margins) and followed up for 3 years, the presence of involved margins and oncogenic-HPV types detection on follow-up were associated with an increased risk of progressive disease.[3][4]

In a cohort of women who had follow-up including colposcopy and endocervical curettage every 6 months, residual disease was subsequently diagnosed in 55% of 20 women who had involved margins at baseline and 28.6% of the 21 women who had free margins at baseline. Twelve of the 13 women who underwent hysterectomy for persistent positive margins had residual disease including four adenocarcinomas and one squamous cell carcinoma.[3] Follow-up using HPV testing had a higher sensitivity and better negative predictive value than cytology when using a colposcopy and histology reference standard.[3] Sensitivity and negative predictive values were further improved when co-testingHPV test and LBC both requested and performed on a cervical sample. was used. These findings demonstrate that colposcopy has limited ability to detect glandular disease. In this study of 42 AISAdenocarcinoma in situ cases, the initial colposcopy was normal in 16% of cases and the squamocolumnar junctionThis is the junction where the ectocervical squamous epithelium and the endocervical columnar epithelium meet, and may be located on the visible ectocervix or may be within the endocervical canal. was not visible in 55% cases.

The findings are described in more detail in the Technical report.

Although the evidence is limited, the findings suggest that women with AISAdenocarcinoma in situ and clear margins can be safely followed up by annual co-testingHPV test and LBC both requested and performed on a cervical sample. for at least 3 years.

There was no evidence comparing completion hysterectomy with ongoing surveillance by co-testingHPV test and LBC both requested and performed on a cervical sample.. However, hysterectomy is not routinely required, based on expert opinion.

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Recommendations

Flowchart 11.4. Follow up after excisional treatment for AISAdenocarcinoma in situ

Follow up after excisional treatment for AIS.PNG




Consensus-based recommendation*Question mark transparent.png

REC11.13: Follow-up of completely excised AISAdenocarcinoma in situ
Women with histologically confirmed AISAdenocarcinoma in situ who have undergone complete excision with clear margins should have annual co-testingHPV test and LBC both requested and performed on a cervical sample. indefinitely.

If any abnormal result is obtained on follow-up co-testingHPV test and LBC both requested and performed on a cervical sample., the woman should be referred for colposcopic assessment.

Until sufficient data become available to support cessation of testing.

Consensus-based recommendation*Question mark transparent.png

REC11.14: Repeat excision for incompletely excised AISAdenocarcinoma in situ
If AISAdenocarcinoma in situ is incompletely excised (positive endocervical margin and/or deep stromal margin, not ectocervical margin) or if the margins cannot be assessed, further excision to obtain clear margins should be performed.

Consensus-based recommendationQuestion mark transparent.png

REC11.15: Role of hysterectomy in AISAdenocarcinoma in situ
In women who have been treated for AISAdenocarcinoma in situ by excision, with clear margins, there is no evidence to support completion hysterectomy. In this situation, hysterectomy is not recommended.

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Benefits and harms

Long-term surveillance after treatment for AISAdenocarcinoma in situ will provide women with reassurance about detecting recurrent AISAdenocarcinoma in situ and thus preventing invasive disease.

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 has been shown to be a very good predictor of recurrent disease over the few years following treatment. Conversely, a HPV test in which oncogenic HPV is not detected has been shown to be a very good predictor of absence of recurrent disease over the few years following treatment in women with complete excision of AISAdenocarcinoma in situ. This supports a surveillance approach using co-testingHPV test and LBC both requested and performed on a cervical sample. which will provide reassurance to women.

Women who persistently have a positive oncogenic HPV test result, but have no cytological abnormality suggestive of glandular disease, will be referred for colposcopic assessment to exclude occult disease. This recommendation may result in colposcopy for some women who would not have developed a clinically significant endocervical glandular lesion, with potential harms including the physical and psychological harms associated with colposcopy. However, this, should be offset against the additional reassurance provided by referral in this situation.

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

The recommended Test of Cure for women treated for AISAdenocarcinoma in situ using annual co-testingHPV test and LBC both requested and performed on a cervical sample. will lead to more intensive surveillance than under 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. However, this will enable the collection of valuable data on AISAdenocarcinoma in situ recurrence and its detection, which will inform future practice.

Eventually, when more accurate risk assessment is possible, long-term surveillance may not be necessary for women who complete a specified duration of Test of Cure. Until more information is available, however, follow-up will be for an indefinite period.

Resourcing

Indefinite follow-up for AISAdenocarcinoma in situ now involves co-testingHPV test and LBC both requested and performed on a cervical sample. rather than cytology alone (as in the pre-renewal program), so more HPV tests will be performed in follow-up to enable management of this relatively small group.

Whilst at this time indefinite co-testingHPV test and LBC both requested and performed on a cervical sample. is recommended, the ongoing monitoring 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. may provide data in the future to support the safety of discharging women who have had a negative co-testHPV test and LBC both requested and performed on a cervical sample. on multiple occasions at an earlier point.

Barriers to implementation

Women may not understand the importance of long-term surveillance for treated AISAdenocarcinoma in situ and may fail to attend for test of cure. It will be important to educate women, and their health professionals, about the importance of long-term surveillance.

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References

  1. 1.01.1 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.
  2. Massad LS, Einstein MH, Huh WK, Katki HA, Kinney WK, Schiffman M, et al ;American Society for ColposcopyThe examination of the cervix and vagina with a magnifying instrument called a colposcope, to check for abnormalities. and Cervical Pathology Consensus Guidelines Conference. 2012 updated consensus guidelines for the management of abnormal cervical cancer screening tests and cancer precursors. J Low Genit Tract Dis 2013 Apr;17(5 Suppl 1):S1-S27 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/23519301.
  3. 3.03.13.23.3 Costa S, Negri G, Sideri M, Santini D, Martinelli G, Venturoli S, et al. Human papillomavirus (HPV) test and PAP smear as predictors of outcome in conservatively treated adenocarcinoma in situ (AIS) of the uterine cervix. Gynecol Oncol 2007 Jul;106(1):170-6 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/17481701.
  4. 4.04.1 Costa S, Venturoli S, Negri G, Sideri M, Preti M, Pesaresi M, et al. Factors predicting the outcome of conservatively treated adenocarcinoma in situ of the uterine cervix: an analysis of 166 cases. Gynecol Oncol 2012 Mar;124(3):490-5 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/22188786.
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Appendices

Jutta's magnifying glass icon.pngPICO questions 7 & 17 View Systematic review report q 7View Systematic review report q 7 View Systematic review report q 17View Systematic review report q 17 View General evidence summary table q 7General evidence summary table q 7
View General evidence summary table q 17General evidence summary table q 17
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