Papillomaviruses

Papillomaviruses are a large group of non-enveloped, double-stranded DNA viruses in the family Papillomaviridae. They infect epithelial tissues of humans and many animals. The genome is a circular ~8 kilobase pair molecule encoding early regulatory proteins (E1, E2, E4, E5, E6, E7) and late structural proteins (L1, L2). E6 and E7 oncoproteins can interfere with p53 and RB pathways, contributing to deregulation of the cell cycle in high-risk types.

Most infections are asymptomatic and cleared by the immune system. Some produce benign warts on skin or mucosal surfaces; others lead to persistent infections. Mucosal HPVs infect the genital, anal, oropharyngeal epithelia, while cutaneous types affect the skin, with disease manifestations ranging from warts to malignant transformation in rare cases.

High-risk HPV types, notably 16 and 18 (often with 31, 33, 45 among others), are associated with cancers of the cervix, anus, penis, and oropharynx. Low-risk types such as 6 and 11 cause genital and laryngeal warts. The oncogenic risk stems in part from expression of E6 and E7 in infected cells, which can disrupt tumor-suppressor pathways.

Transmission occurs mainly through sexual contact for mucosal infections and through skin-to-skin contact for cutaneous infections; vertical transmission during birth can occur but is uncommon. The viral life cycle is linked to epithelial differentiation: virus infects basal cells, persists as an episome, and productive replication occurs in suprabasal cells with assembly and release of virions in the superficial layers.

Prevention relies on vaccines based on virus-like particles from the L1 major capsid protein. Prophylactic vaccines (Gardasil 9, Cervarix) cover multiple HPV types and are recommended for preteens and sexually active individuals where not already infected. Screening with cervical cytology (Pap tests) and HPV DNA testing supports early detection.

The role of papillomaviruses in cancer was established by research led by Harald zur Hausen, for which he received the Nobel Prize in 2008.