Genetic and familial high-risk assessment in cervical cancer

Cervical cancer remains a major public health concern worldwide, despite the well‐established causal role of high‐risk human papillomavirus (HPV) infection in its pathogenesis. Although HPV infection is necessary for the development of cervical neoplasia, only a fraction of infected women progress to invasive cancer. Emerging evidence indicates that host genetic factors, including familial clustering and specific genetic variants, significantly modulate individual susceptibility to both HPV persistence and progression to cervical cancer. This perspective reviews current evidence on genetic susceptibility and familial risk in cervical cancer, spanning common low-penetrance variants identified through genome-wide association studies and rare high-penetrance hereditary syndromes such as Lynch syndrome, Peutz–Jeghers syndrome, and WHIM syndrome. We discuss how these genetic factors contribute to cervical cancer heterogeneity and highlight their potential clinical relevance. In particular, genetic risk stratification may complement HPV-based screening by enabling more individualized surveillance strategies, such as tailored screening intervals and targeted follow-up in women at elevated risk.