PRIMEVIEW

CARCINOGENIC HPV INFECTION

For the Primer, visit doi:10.1038/nrdp.2016.86

Of the >200 known human PREVENTION

DIAGNOSIS
papillomavirus (HPV) genotypes,
13 are deemed high risk and associated
Three vaccines are
with human diseases — notably,
currently available that
cervical, vaginal, vulvar, penile, anal and Several tests
provide coverage against
oropharyngeal cancers. These high-risk and strategies
have been developed several high-risk HPVs:
types belong to the Alpha genus of HPV.
to assess the cervix and The Papanicolaou a bivalent vaccine that
predict the risk of cancer (‘Pap’) cytology offers protection from HPV16 and HPV18,
of a given HPV lesion, screen is widely used, which are responsible for most HPV cancers; a
MECHANISMS many of which are in but HPV DNA testing is tetravalent vaccine, which provides coverage
use internationally.
being incorporated (or even against HPV16, HPV18, HPV6 and HPV11
HPV infections are common and primarily recommended to replace (HPV6 and HPV11 commonly cause genital
transmitted by sexual contact. The virus mainly cytology as the screen) into warts); and a nonavalent vaccine that provides
infects epithelial and mucosal tissues and regulates the technique. protection against HPV16, HPV18, HPV6,
gene expression as the infected basal cell migrates HPV11, HPV31, HPV33, HPV45, HPV52 and
towards the epithelial surface. The carcinogenicity The cervical intraepithelial HPV58. In countries that have implemented a
of HPVs results predominantly from the activity of neoplasia tripartite scale vaccination programme with >50% coverage of
the oncoproteins E6 and E7, which are viral proteins (CIN1–CIN3) is the most adolescent girls, herd protection against genital
that impair growth regulatory pathways in the host common histopathology HPV infections and warts has been later shown
system used in diagnosis
cell. E6 and E7 expression increase as an infection in heterosexual women and men.
and is based on the A clinically
transitions from a productive (virion-producing) fraction of epithelium more-meaningful
to an abortive (transforming) state, after which replaced by approach would be
cancer can result following the accumulation of host undifferentiated tissue classification
genetic mutations over many years. Most infections cells. MANAGEMENT
according to HPV
(even those of high-risk Alpha HPVs) are controlled status: normal (no
immunologically and cleared by the host, such that HPV detected), Cervical precancers are typically excised or
viral DNA or RNA is undetectable within 2 years. precancer (a lesion ablated. Anogenital cancers are preferentially
However, which infectious precancerous lesions with a very high treated with radical local excision (for example,
can be immunologically cleared and which progress probability of invasion hysterectomy for cervical cancer) and, when the
cannot be accurately predicted. Although many if untreated) or cancer. risk of spread to the lymph nodes is high, with
systems and nomenclatures have been devised to
characterize precancerous lesions with the aim of
DNA The cost
of implementing HPV,
regional lymphadenectomy. For early-stage
anogenital cancers, radiotherapy is an acceptable
guiding treatment, overtreatment of potentially DNA or RNA testing (and primary therapy; platinum-based chemotherapy
benign lesions is common.
RNA replacing current pathology
systems) is potentially
can also be given. However, in advanced-stage,
metastatic cancer, treatment outcomes are
Normal HPV Precancer Cancer controversial.
epithelium infection universally poor and focus shifts to palliation.
EPIDEMIOLOGY

Cervical cancer is the most
common HPV-related cancer,
with >500,000 cases reported
in 2012. Indeed, the fraction of
HPV-induced cancers in men
is much lower (<1%) than in
women (8.6%) because of the
unique vulnerability of the
cervix. However, the rates of
cervical cancer vary greatly
between geographical regions
owing to the combined effect of
Currently, HPV
status of the tumour
prevalence of cervical HPV does not influence
infection and quality of cervical treatment strategy
for any HPV‑related
cancer screening programmes in
anogenital cancer
different countries.

Written by Mina Razzak; designed by Laura Marshall Article number: 16087; doi:10.1038/nrdp.2016.87; published online 1 Dec 2016
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