Human Papillomaviruses (HPVs)

HPVs are epitheliotropic viruses with double-stranded DNA genomes
and eight coding genes defined as “early” or “late” depending on when
they are expressed. Over 200 HPVs have been identified with 13 types
considered oncogenic or high risk (HR). HPV type 16 confers the
greatest risk, being responsible for around 60% of cervical cancers.
HPV infection is common with a global point prevalence of around
10% and most infections are transient. The life cycle of HPV is inextricably
linked with squamous epithelial differentiation and, during a
productive infection, involves tightly regulated sequential gene expression
at the separate epithelial layers before particle release. Some persistent
infections can lead to cancer; in this scenario the productive life
cycle is not completed, and deregulated expression of early oncoproteins
E6 and E7 stimulates uncontrolled cellular proliferation while
abrogating tumor suppressor function.
Prophylactic HPV immunization and the use of molecular HPV testing
as a primary cervical screening test have been implemented in several settings.
Immunization has led to a significant decrease in HPV infection and
associated disease at the population level, and the high sensitivity and
reproducibility of HPV testing enables screening intervals to be extended
(for those who test negative) and provides options for self-sampling.
Future challenges will include how to integrate and implement immunization
and contemporary screening practices most optimally.