Human papillomavirus (HPV) is the leading etiological factor in the development of intraepithelial neoplasia’s and malignant neoplasms of the anogenital region. A distinctive clinical feature of the HPV-associated process is its propensity to form multifocal lesions, in which neoplasia’s of different anatomical sites – the cervix, vagina, vulva, and anal canal (CIN, VAIN, VIN, and AIN) – are detected either synchronously or metachronously during follow-up. Despite the high prevalence of this phenomenon, its pathogenetic basis remains a subject of debate. Existing interpretations predominantly regard such lesions as a set of independent local processes. In recent years, accumulating evidence has shown that HPV is capable of establishing persistent populations of infected cells that retain proliferative potential over extended periods. These changes create conditions for long-term viral persistence in epithelial tissues and maintenance of subclinical infection. In this context, multifocal HPV-associated lesions can be considered a manifestation of a single pathological process driven by prolonged viral persistence in the anogenital epithelium. Analysis of these mechanisms is of considerable interest for understanding the patterns of HPV infection spread, the development of multifocal neoplasia’s, and their clinical course. Multifocal HPV-associated lesions of the anogenital region reflect the complex, multilevel nature of the underlying pathogenesis and create significant challenges for their timely detection. In this setting, optimization of patient management requires a comprehensive diagnostic approach, including advanced visualization techniques, morphological and molecular-biological verification, as well as the development of personalized risk stratification strategies. These strategies aim to prevent disease progression and reduce the recurrence rate of precancerous lesions in the anogenital area.