Human papillomavirus (HPV)

About Human Papillomavirus Human papillomaviruses (HPVs) are small, non-enveloped double-stranded DNA viruses in the family Papillomaviridae. More than 200 HPV types have been identified, and they primarily infect cutaneous or mucosal epithelial cells. HPV types are classified mainly by nucleotide sequence relatedness in the L1 gene and are distributed among several genera, including Alphapapillomavirus, Betapapillomavirus, and Gammapapillomavirus. The virion is approximately 55 nm in diameter and contains a T=7d icosahedral capsid composed primarily of the major capsid protein L1, with smaller amounts of the minor capsid protein L2. L1 forms pentameric capsomers and can self-assemble into virus-like particles, while L2 contributes to genome packaging, entry, intracellular trafficking, and delivery of viral DNA to the nucleus. The circular HPV genome is approximately 8 kb and is maintained as an episome during productive infection. Viral replication is closely linked to epithelial differentiation: early genes are expressed in basal and suprabasal cells, while high-level genome amplification, capsid-protein production, and virion assembly occur in more differentiated epithelial layers.

Mucosal HPV types are commonly grouped as low-risk or high-risk according to their association with cancer. Low-risk types such as HPV6 and HPV11 are frequently associated with anogenital warts and rarely cause cancer. Persistent infection with high-risk types can lead to precancerous lesions and malignancies of the cervix, anus, vulva, vagina, penis, and oropharynx. HPV16 and HPV18 account for the largest proportion of HPV-associated cancers.

In high-risk HPV types, the E6 and E7 oncoproteins promote continued cell-cycle progression and interfere with key tumor-suppressor pathways. E6 can direct degradation of p53 through the E6AP ubiquitin ligase, while E7 binds and inactivates retinoblastoma-family proteins. These activities support viral genome amplification in differentiating epithelial cells and, during persistent infection, can contribute to genomic instability and malignant progression.

The HPV genome contains an upstream regulatory region, an early region, and a late region. The early region encodes proteins involved in replication, transcriptional control, cell-cycle regulation, immune modulation, and productive infection. The late region encodes the structural capsid proteins L1 and L2. All major open reading frames are transcribed from one DNA strand, and extensive alternative splicing expands the range of viral products.