The Role of Methylation of Host and/or Human Papillomavirus (HPV) DNA in Management of Cervical Intraepithelial Neoplasia Grade 2 (CIN2) Lesions

Round 1

Reviewer 1 Report

Dovnik and Poljak review the role of host and viral DNA methylation in CIN2 management. They weigh up the wider impact of surgical approaches on younger patients, given the typical population, and identify the potential of methylation markers as a triage tool.

Overall this review is well written and comprehensive. The authors present a compelling argument that methylation analysis of virus and host combined will be a useful tool in managing CIN2, and I appreciate the overview of promising assays being presented in table form.

I have no criticisms or alterations to be made for this manuscript. For my own interest, I would find it interesting to discuss whether the different HPV types affect host methylation markers to different extents, but I realise that this may be out of the scope of the review.

Reviewer 2 Report

In this manuscript, the authors perform a systematic review where they first summarize the current knowledge regarding conservative management of CIN2 lesions. They then comprehensively describe ongoing studies dealing with the role of methylation marker assessment in dictating management of precancerous lesions.

This reviewer thought the manuscript was comprehensive and detailed the studies appropriately. This will be of interest to the subfield of HPV that is interested in prognostic markers and/or methylation. I recommend this manuscript for publication.