Cervical HPV

Epidemiology

 Genital HPV is the most common sexually transmitted disease (S D) in the United States.
 Most incident HPV infections develop in women younger than 25 years.
 Clinically, HPV types are classified as high-risk (HR) or low-risk (LR) based on their strength of
association with cervical cancer.
 LR HPV types 6 and 11 cause nearly all genital warts are rarely oncogenic.

 HR HPV types, including 16, 18, 31, 33, 35, 45, and 58, along with a few less common types,
account or approximately 95 percent of cervical cancer cases worldwide.
 HPV 16 is the most oncogenic, which accounts or more than 1 in 5 cervical HPV infections.
 HPVs 16 and 18 account or approximately 70 percent of cervical cancers worldwide, 68 percent
of squamous cell carcinomas, and 85 percent of adenocarcinomas.

Etiology

 The causative role of HPV in nearly all cervical neoplasia and a significant proportion of vulvar,
vaginal, and anal neoplasia.
 HPV primarily infects human squamous or metaplastic epithelial cells.
 Double-stranded DNA virus with a protein capsid unique to each viral type.


Pathophysiology

 Cervix
o When visible on the ectocervix, the SCJ is a pink, smooth squamous epithelium
juxtaposed against the red, velvety columnar epithelium surrounding the external
cervical os
o The location of the SCJ varies with age and hormonal status.
 During the reproductive years, it everts outward onto the ectocervix, especially
during adolescence, pregnancy, and with combination hormonal contraceptive
use.
 It regresses into the endocervical canal during the natural process of squamous
metaplasia and in low-estrogen states such as menopause, prolonged lactation,
and long-term progestin-only contraceptive use.
 At puberty, the rise in estrogen levels leads to increased glycogenation of the
LGT nonkeratinized squamous epithelium. In providing a carbohydrate source,
glycogen allows vaginal flora to be dominated by lactobacilli, which produce
lactic acid. The resultant acidic vaginal pH is the suspected stimulus or
squamous metaplasia, which is the normal replacement of columnar by
squamous epithelium on the cervix.
  Cervical reserve and immature metaplastic cells appear particularly vulnerable
to the oncogenic effects of HPV and cocarcinogens.
 Squamous metaplasia is most active during adolescence and pregnancy.
This may explain why early ages of first sexual activity and of first
pregnancy are cervical cancer risk actors.

 True HPV lesions tend to be multifocal and asymmetric, and to have multiple papillations arising
from a single base

 incubation period is up to 6 months

Transmission

 Direct contact
 Most important risk factors or the acquisition of genital HPV infection are the number of lifetime
and recent sexual partners and early age at first sexual intercourse.

Clinical Manifestations

 Latent infection refers to that in which cells are infected, but HPV remains quiescent.
o No detectable tissue effects, as the virus is not actively replicating
o Virus is present below detectable levels
 Productive in ections
o Characterized by viral life-cycle completion and plentiful production of infectious viral
particles
o In both female and male genital tracts, productive HPV infections cause either visible
genital warts (condyloma acuminata)
 Neoplastic infection
o Integration of viral genome into the host’s chromosomes
o E6 and E7 oncoproteins produced inter ere with and accelerate degradation of p53 and
pRb, which are key tumor suppressor proteins produced by the host
o This leaves the infected cell vulnerable to malignant transformation by loss of cell-cycle
control, cellular proliferation, and accumulation of DNA mutations over time.

Laboratory Work-up

1. Pap smear
2. HPV testing
3. Cervical Cancer Screening Guidelines
4. Colposcopy
5. Biopsy
6.
Management

Vulvar HPV

 Condylomata acuminata are benign genital warts caused by low oncogenic risk HPVs, mainly
types 6 and 11. They may be solitary, but are more frequently multifocal, and may involve
vulvar, perineal, and perianal regions as well as the vagina and, less commonly, the cervix. The
lesions are identical to those found on the penis and around the anus in males. On histologic
examination, they consist of papillary, exophytic, treelike cores of stroma covered by thickened
squamous epithelium. The surface epithelium shows characteristic viral cytopathic changes
referred to as koilocytic atypia, which manifest as nuclear enlargement, hyperchromasia and a
cytoplasmic perinuclear halo. Condylomata acuminata are not precancerous lesions.
o Papillomavirus-induced lesion

 Classic VIN
o .

 Differentiated VIN
o