Follow-up after excisional treatment for AIS

Guidelines for the pre-renewal NCSP[1] recommended:

• that decisions about management of histologically confirmed AIS should take into account the woman’s age, fertility status, and excision margins
• hysterectomy for women with histologically confirmed AIS who have completed childbearing
• that hysterectomy should not be undertaken as a treatment for AIS 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 AIS 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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Systematic review evidence

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

• completion hysterectomy
• repeat co-testing 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 AIS. 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 AIS to inform the drafting of relevant consensus-based recommendations. Two prospective cohort studies[3][4] reported cancer outcomes for women with histologically confirmed AIS managed conservatively after excisional biopsy. 

For women diagnosed with AIS 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-testing was used. These findings demonstrate that colposcopy has limited ability to detect glandular disease. In this study of 42 AIS cases, the initial colposcopy was normal in 16% of cases and the squamocolumnar junction 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 AIS and clear margins can be safely followed up by annual co-testing for at least 3 years. 

There was no evidence comparing completion hysterectomy with ongoing surveillance by co-testing. However, hysterectomy is not routinely required, based on expert opinion.

Flowchart 11.4. Follow up after excisional treatment for AIS

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

A positive oncogenic HPV (any type) 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 AIS. This supports a surveillance approach using co-testing 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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Clinical practice

The recommended Test of Cure for women treated for AIS using annual co-testing will lead to more intensive surveillance than under pre-renewal NCSP guidelines. However, this will enable the collection of valuable data on AIS 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 AIS now involves co-testing 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-testing is recommended, the ongoing monitoring of the renewed NCSP may provide data in the future to support the safety of discharging women who have had a negative co-test on multiple occasions at an earlier point.

Barriers to implementation

Women may not understand the importance of long-term surveillance for treated AIS 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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