HPV Infection Strongest Predictor of Cervical Precancer Treatment Failure

Meta-analysis sheds light on the impact of human papillomavirus infection and margin status on the likelihood of residual or recurrent high-grade cervical intraepithelial neoplasia of grade 2 or higher

medwireNews: Human papillomavirus (HPV) infection after surgery for precancerous lesions is the most accurate predictor for treatment failure, suggest the results of a meta-analysis.

The researchers collated data from 44,446 women treated for high-grade cervical intraepithelial neoplasia of grade 2 or higher (CIN2+) in one of 97 studies. Eighteen of the 25 studies of margin accuracy that had 18 months of follow-up reported findings for a high-risk HPV test performed 3–9 months after surgery – these gave a pooled sensitivity and specificity for residual or recurrent CIN2+ of 91.0% and 83.8%, respectively.

The study also confirmed earlier findings of a link between a positive surgical margin and treatment failure but this was less accurate, the researchers report in The Lancet Oncology.

“Combined results of the margin and post-treatment HPV status could be used to stratify risk and diversify management”, they write.

“Achievement of negative resection margins needs to be balanced with the depth of cervical excision in women of childbearing age in light of the potential for increased preterm birth risk.”

Data collated from 24 studies with at least 18 months of follow-up showed that positive margins occurred in 23.1% of the women and the rate varied with type of treatment, from 17.8% of laser conisation procedures and 20.2% of cold-knife conisations to 25.9% of large loop excisions of the transformation zone.

In all,6.6% of these patients were subsequently diagnosed with residual or recurrent CIN2+ and rates again varied with type of procedure, from around 2% of cold-knife and laser conisations to almost 7% of large loop excisions.

The risk of residual or recurrent CIN2+ was 17.1% for women with a positive margin after any procedure, ranging from 14.1% for laser conisation of the transformational zone to 25.6% after cold-knife conisation, whereas the risk was just 3.7% for women with a negative margin and this did not vary with procedure.

Thus, the pooled sensitivity and specificity of a positive margin for residual or recurrent CIN2+ was 55.8% and 84.4%, respectively, although the findings were “highly variable”, especially for sensitivity which ranged in the studies from 9.1% to 94.1%, emphasize Marc Arbyn, from the Scientific Institute of Public Health in Brussels, Belgium, and co-investigators.

“The finding from our review showing that free margins are associated with higher cure rates, together with knowledge that older women have higher risks of recurrent CIN2+, might justify recommendations for more aggressive treatment at ages at which reproductive safety is no longer an issue”, the authors conclude.

“Suspicion of invasive cancer, presence of glandular precancer, and unsatisfactory colposcopy are other indications for which gynaecologists might decide to do a large excision.”


Arbyn M, Redman CW, Verdoodt F, et al. Incomplete excision of cervical precancer as a predictor of treatment failure: a systematic review and meta-analysis. Lancet Oncol; Advance online publication 7 November 2017. DOI: http://dx.doi.org/10.1016/S1470-2045(17)30700-3


medwireNews is an independent medical news service provided by Springer Healthcare. © 2017 Springer Healthcare part of the Springer Nature group