CADM1 and MAL methylation status in cervical scrapes is representative of the most severe underlying lesion in women with multiple cervical biopsies

Recent studies have shown that CADM1/MAL methylation levels in cervical scrapes increase with severity and duration of the underlying cervical intraepithelial neoplasia (CIN) lesion. Multiple lesions of different histological grades and duration are frequently present on the cervix. To gain more insight into the possible epigenetic heterogeneity and its consequences for the methylation status in cervical scrapes, we performed an exploratory study of CADM1/MAL methylation in different grades of CIN lesions present in women with multiple cervical biopsies. CADM1‐M18 and MAL‐M1 methylation was assessed using a standardised, multiplex, quantitative methylation specific PCR on 178 biopsies with various grades of CIN in 65 women, and in their corresponding cervical scrapes. CADM1/MAL methylation positivity increased with disease severity, from 5.5% in normal biopsies to 63.3% and 100% in biopsies with CIN3 and cervical cancer, respectively. In the majority (8/9) of women where besides a CIN2/3 lesion a biopsy from normal cervical tissue was present, the CIN2/3 biopsy was CADM1/MAL methylation positive and the normal biopsy was CADM1/MAL methylation negative. A good concordance (78%) was found between CADM1/MAL methylation results on the scrapes and the biopsy with the worst diagnosis, particularly between samples of women with CIN3 and cervical cancer (92% and 100% concordance, respectively). Thus, in women with multiple cervical biopsies, CADM1/MAL methylation increases with severity of the lesion and is lesion‐specific. CADM1/MAL methylation status in cervical scrapes appears to be representative of the worst underlying lesion, particularly for CIN3 and cervical cancer. What's new? When screening for cervical cancer, various characteristics can provide information. For instance, some results have shown that the degree of methylation in the CADM1/MAL genes can indicate how long an HPV infection has been present. The more methylated, the more severe the pre‐cancerous lesion (CIN). But what if the patient has multiple lesions? The results of this study confirmed that more advanced lesions did show more methylation. The authors then went on to demonstrate that the methylation status detected in cervical scrapes seems to correspond with the most advanced lesions present on the cervix, especially cervical cancer or CIN3.