Human papillomavirus-human immunodeficiency virus coinfection and host cell DNA methylation in vulvar carcinogenesis

Abstract

Vulvar cancer accounts for about 5% of all gynaecological malignancies. Previously, it was regarded as a disease of the elderly because it occurred in women over 60 years old. Its incidence is rising due to the coinfection of human papillomavirus (HPV) and human immunodeficiency virus (HIV). High-risk HPV (HR-HPV) predominantly drives both the premalignant and invasive diseases of the vulva in the young population. Women living with HIV have compromised immunity, and the synergism of HPV and HIV might be responsible for their higher predisposition to anogenital neoplasia. They are at a higher risk of infection with multiple HPV genotypes, multifocal disease, persistent infection, and reactivation of latent infections. Genomic alteration through deoxyribonucleic acid (DNA) methylation by persistent HPV infection is implicated in carcinogenesis through the E6/E7 oncogenic pathway. These epigenetic alterations progressively accumulate in HPV-infected cells and induce cancers over time. Premalignant lesions that display abnormal methylation patterns similar to those in cancerous lesions are likely to progress to malignancy within a short period. Such methylation biomarkers can be used to triage premalignant lesions to treatment or monitoring. This review describes the distribution of HPV genotypes and host cell DNA methylation patterns across vulvar premalignant and invasive lesions.