Cervical cancer is preventable and curable as long as it is detected early and managed effectively. However, treatment of precancerous lesions carries a risk of obstetric complications that can impact future pregnancy. Researchers at Cancer Center Amsterdam have discovered that DNA methylation of certain genes from host cells can help guide risk assessment and support a wait and see policy. The study was published in the Journal of Clinical Oncology.

Most cases of cervical cancer, a type of cancer that occurs in the cells of the uterine cervix, are caused by certain types of the human papillomavirus (HPV), a sexually transmitted infection.

HPV vaccination protects against new HPV infections, but cervical screening remains an important secondary prevention method for early detection and treatment to prevent cervical intra-epithelial neoplasia (CIN) from becoming cancerous.

Precancerous lesions

When exposed to HPV, the body's immune system typically prevents the virus from doing harm. In some people, however, the virus persists for years, contributing to the process that causes cervical cells to become precancerous lesions that, without treatment, can lead to cervical cancer.

The goal of management is to prevent possible progression to cancer while avoiding overtreatment, since spontaneous regression of CIN lesions (of grade 2 or 3, CIN2/3) frequently occurs and treatment can have morbid effects.

Until recently, regression of CIN2/3 lesions could not be effectively predicted.

Clues in the DNA

A new publication in Journal of Clinical Oncology by Cancer Center Amsterdam researchers demonstrates that examining the methylation status of the DNA in cells from CIN2/3 lesions can predict the risk of progression.

Clinical regression of CIN2/3 was found to be significantly associated with absence of DNA methylation of host cell genes FAM19A4 and miR124-2 in clinician-collected and self-collected samples.

Two-year clinical regression in women with a negative FAM19A4/miR124-2 methylation test result on the baseline clinician-collected sample was 74.7%, significantly higher than in women with a positive methylation result (51.4%, P = .013).

A better Wait and See policy

These findings highlight new opportunities for a wait-and-see policy in women with CIN2/3 who have a negative FAM19A4/miR124-2 methylation test on a clinician-collected or self-collected sample. The methylation test combined with cytology and human papillomavirus genotyping can further refine the risk prediction. This policy is particularly of interest for women of reproductive age to minimize the risk of obstetric complications.

For more information see https://www.hpvstudies.nl/ or read the publication:

Kremer, W.W., et al (2022) Clinical Regression of High-Grade Cervical Intraepithelial Neoplasia Is Associated With Absence of FAM19A4/miR124-2 DNA Methylation (CONCERVE Study). J. Clin. Oncol. https://ascopubs.org/doi/full/10.1200/JCO.21.02433

Involved researchers:

Wieke W. Kremer

Stèfanie Dick

Daniëlle A.M. Heideman

Renske D.M. Steenbergen

Maaike C.G. Bleeker

Chris J.L.M. Meijer

Johannes Berkhof

This work was supported by ZonMw, grant No. 531002010 and the European Union's Horizon 2020 Research and Innovation Programme under grant agreement No. 847845 (RISCC project).