A risk-based approach for post-treatment detection of recurrent CIN

By Rebecca Millecamps, Fujirebio
 

Women who are treated for CIN2/3 remain at increased risk of recurrent CIN and cervical cancer. Therefore, strategies to monitor these women after treatment are implemented in many countries. The most common posttreatment surveillance method to detect recurrent CIN include HPV testing and/or cytology. Methylation markers are promising tools for reliable posttreatment detection of recurrent CIN2/3 with a persistent HPV infection following treatment of high-grade CIN. Unnecessary interventions should be avoided, since (re)treatment of CIN is associated with an increased risk of obstetric complications.

This article describes how HPV genotyping and DNA methylation analysis can help discriminate women in need of re-treatment from those who can be managed conservatively to prevent overtreatment. 

The article is part of a series of resources dedicated to the state-of-the-art of HPV testing. 
Get a full overview of our resources here. 

Treatment of high-grade cervical intraepithelial neoplasia (CIN2/3) is effective in preventing subsequent invasive cervical cancer, but despite treatment these women remain at increased risk of developing a new CIN for the next 25 years compared to the general population. The majority of cases develop within the first two years after treatment and approximately 7% of treated women are diagnosed with recurrent disease during the 18-month follow-up period. In view of the substantial risk of recurrent disease, effective post-treatment testing is mandatory.^1,2,3,4,5,6

Careful clinical surveillance is a necessary condition for effectiveness of conservative treatments of cervical intraepithelial neoplasia (CIN) from both a clinical and a public health perspective.  The rate of patients lost to follow-up is often not documented, although figures as high as 25% have occasionally been observed.⁷

Recurrent cervical high-grade lesions – a heterogenous group

Recurrent cervical high-grade lesions represent a heterogenous group, including either persisting lesions resulting from incomplete treatment (residual lesions) or newly develop lesions (incident  lesions). Most of the recurrent high-grade lesions diagnosed within two years of surgery are actually residual lesions. Several factors influence the recurrence of high-grade lesions.  For example, a persistent HPV16 infection is associated with a greater rate of relapse after conisation of CIN2+ with respect to the other high risk HPV genotypes.^13,14

Persistent versus new HPV infection

The strong etiological link between persistent high-risk HPV-infection and the development of cervical cancer is clear. A new infection of a different HPV genotype gives a relatively low future risk, given the probability of clearance of the infection and the long interval after HPV infection before the development of an invasive cancer. A negative high-risk HPV result has a superior negative predictive value (NPV) compared with negative cytology or negative resection margins. Posttreatment negative co-testing avoids an additional 8.4 cases of CIN3 or worse per 1,000 women treated and reduce health care costs, compared with negative cytology alone.¹²