Follow-up strategies for women following treatment for CIN: Impact of HPV testing

Background

It is widely accepted that infection with high-risk human papillomavirus (hrHPV) is associated with development of precancerous changes, namely, cervical intraepithelial neoplasia (CIN) and cervical cancer. It is also accepted that women who develop high-grade CIN and subsequently receive treatment with a procedure called large loop excision of the transformation zone (LLETZ), which uses a wire loop to remove abnormal cells, are at greater risk for developing further CIN than women who have never had CIN. Therefore, these women need regular follow-up assessment to detect additional abnormalities.

Main findings

We searched for randomised control trials (RCTs) that compared follow-up management strategies following LLETZ treatment for CIN. We checked 1348 titles and abstracts of potentially relevant references, but we identified no randomised controlled trials (RCTs) that met our inclusion criteria. We identified trials of interest, but they were deemed not relevant because of their focus on diagnostic outcomes and examination of how sensitive tests are, rather than on the effects of different follow-up strategies on long-term outcomes. Currently no evidence indicates whether hrHPV post-treatment testing is better or worse in terms of important long-term clinical outcomes. This review highlights the need for good quality trials in this area that do not focus solely on the diagnostic accuracy of testing.

Conclusion

We found no evidence from RCTs to inform decisions about the best surveillance strategy following treatment for CIN. A prognostic systematic review is needed to investigate the risks and benefits of different follow-up strategies for women after LLETZ treatment.

Authors' conclusions: 

We found no evidence from RCTs to inform decisions about the best surveillance strategy for women following treatment for CIN. A prognostic systematic review is needed to investigate the risk of developing recurrent cervical intraepithelial neoplasia 2+ (CIN2+) in women with a positive hrHPV test after large loop excision of the transformation zone (LLETZ) treatment.

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Background: 

Development of cancer of the cervix is a multi-step process as before cervical cancer develops, cervical cells undergo changes and become abnormal. These abnormalities are called cervical intraepithelial neoplasia (CIN) and are associated with increased risk of subsequent invasive cancer of the cervix. Oncogenic high-risk human papillomavirus (hrHPV), the causative agent of cervical cancer and its precursor lesions, is present in up to one-third of women following large loop excision of the transformation zone (LLETZ) treatment and is associated with increased risk of residual disease and disease recurrence. HPV testing may serve as a surveillance tool for identifying women at higher risk of recurrence. High-risk human papillomavirus testing will enable us to identify women at increased risk of residual or recurrent CIN and therefore will allow us to offer closer surveillance and early treatment, when indicated.

Objectives: 

• To evaluate the effectiveness and safety of hrHPV testing after large loop excision of the transformation zone (LLETZ) treatment
• To determine optimal follow-up management strategies following LLETZ treatment according to hrHPV status

Search strategy: 

We searched the Cochrane Gynacological Cancer Review Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), PubMed and PsycINFO up to August 2013. We searched registers of clinical trials, abstracts of scientific meetings and reference lists of included studies, and we contacted experts in the field.

Selection criteria: 

We searched for randomised control trials (RCTs) that compared follow-up management strategies following LLETZ treatment for CIN.

Data collection and analysis: 

Two review authors independently assessed whether potentially relevant studies met the inclusion criteria. No trials were found; therefore no data were analysed.

Main results: 

The search identified 813 references on MEDLINE, 418 on EMBASE, 22 on CINAHL, 666 on PubMed, 291 on PsycINFO and 145 on CENTRAL. When all references were imported into EndNote and duplications were removed, 1348 references remained. Initial screening of titles and abstracts of these references revealed that 42 references were potentially eligible for this review. After reading the full-text versions, we identified no relevant trials comparing hrHPV and cytology testing versus cytology testing alone for detecting residual or recurrent disease during follow-up to LLETZ treatment of adult women with CIN.

We found no evidence on the effects of hrHPV and cytology testing on residual or recurrent CIN2 or higher lesions, anxiety and psychosexual morbidity outcomes in women undergoing colposcopy and treatment for CIN.