Human Papillomaviruses: Benign and Malignant Disease

Papillomaviruses are extremely widespread, small, nonenveloped, icosahedral, species-specific, double-stranded DNA epitheliotropic viruses, which include human papillomaviruses (HPVs) only infecting humans. HPVs establish chronic epithelial infections, with various genotypes associated with infection at specific anatomic sites. Of greatest importance are oncogenic (“high risk” [HR]) HPVs, the etiological agent of many upper and lower genital tract neoplasias, especially cervical, as well as a sizeable proportion of oropharyngeal carcinomas. HPV-6/11 causes most genital warts and recurrent respiratory papillomatosis. In clinical trials and/or in real-world settings, prophylactic HPV vaccines (2–9 valent) have resulted in significant reductions in circulating infection, with vaccine-related genotypes and in associated diseases (genital warts, precancerous lesions, and cancer itself). Maximizing these outcomes requires high vaccine coverage of the target population. The WHO global cervical cancer elimination strategy aims to make cervical cancer a rare disease (incidence < 4 per 100,000). Scale-up targets to be achieved by 2030 are known as the “90-70-90” targets (90% of young girls fully vaccinated by 15 years of age, 70% of women receive high-precision cervical screening at least twice by 45 years of age, and 90% of those with cervical lesions/cancer receive treatment). Because countries with the least resources bear the heaviest burden of HPV-related disease, achieving global equity as envisioned by WHO is a major challenge: As of 2023 only 13% of young girls eligible for HPV vaccination are fully vaccinated and two-thirds of 30- to 49-year-old women have never had cervical screening.