Human papilloma virus (HPV) affects nearly 25% of Americans and is a key trigger for cervical cancer (CC), which remains a leading cancer among women globally. Diagnosis often involves cytology screenings and HPV testing, while treatment options vary from surgery to chemoradiation, with a 5-year survival rate of approximately 67.1%. Prevention through vaccination and safe sexual practices is critical, as a 9-valent vaccine can protect against multiple high-risk HPV types associated with CC.

1. Nearly one in four Americans are infected with human papilloma virus (HPV) – the main sexually acquired trigger
for cervical cancer (CC). Between 1975 and 2010, the diagnosis of the illness decreased by more than 50% in the
USA. However, CC continues to be the fourth most common malignancy among women worldwide and is the most
common cancer in women in East and Middle Africa. CC is estimated to cause 266,000 deaths annually.
1. Definition
This mostly-vaccine-preventable illness starts in the cells lining the cervix ie, lower part of the uterus. Typically,
CCs start as pre-cancers which, in some women, can transform into invasive CCs. Histopathologic subtypes
include squamous cancers (80%), adenocarcinomas (15%), adenosquamous (3% to 5%), and rare neoplasms
(transitional cell, neuroendocrine, small cell, adenoid cystic, mesonephric, adenoma malignum, lymphoma,
sarcoma). These microscopic features do not alter staging, but may affect treatment and prognosis.
2. Diagnosis
Apart from HPV, multiple sexual partners, HIV, early onset of sexual activity, cigarette smoking, and
immunosuppression may also be triggers for CC. Abnormal liquid-based cytology screening or a Pap smear
may be the first indication of asymptomatic disease. A differential diagnosis may involve additional tests eg,
HPV test (13 of the 100 known strains are cancer-causing; HPV 16 and 18 cause 70% of cervical cancers and
precancerous cervical lesions) as well as colposcopy and a biopsy for symptomatic females.
3. HPV and cancer
Sexually transmitted variants of this DNA tumor virus fall into low- and high-risk categories. Low-risk HPVs
cause warts around the genitals or anus e.g., 90% of all genital warts are caused by HPV types 6 and 11.
About 95% of anal and 70% of oropharyngeal cancers have been linked to HPV. Rarer cancers associated
with HPV include vaginal, vulvar, and penile cancers (mostly caused by HPV type 16). High-risk HPV types
are associated with ~5% of cancers across the globe.
4. Treatment
While preinvasive lesions may spontaneously regress, it is worth noting that untreated CC is uniformly
fatal. Treatment plans recommended by the The American Society of Clinical Oncology are stratified
based on resource settings, and range from basic or limited to enhanced or maximal. Options range
from cryosurgery and a loop electrosurgical excision procedure (LEEP/LEETZ) to a radical hysterectomy
or chemoradiation. The 5-year relative survival rate of 67.1% (2007-2013) and declining fatalities in the
USA indicate that guideline-recommended care works for many American women.
5. Emerging Therapies
Small molecule inhibitors that target PIK3CA mutations may be useful in up to 36% of advanced or recurrent
tumors. Cediranib has been found to have significant efficacy when added to carboplatin and paclitaxel in the
treatment of metastatic or recurrent cervical cancer in a single trial setting. Preclinical and preliminary data for
erlotinib and cetuximab have been encouraging. Other investigative options include nerve-sparing surgical
techniques, radiation alone, immunotherapies, gene therapy, neoadjuvant, and adjuvant chemotherapies.
6. Follow-Up Care
Most CC recurrence occurs within the first 2 years. Currently, guideline recommendations from the National
Comprehensive Cancer Network are to monitor for local recurrence with 3- to 6-monthly clinical review, physical
exam, and cervical/vaginal cytology in the first 2 years, then every 6 to 12 months for 3 to 5 years. In addition to
encouraging patients to report significant symptoms (pain, bleeding, swelling) early, patient education and
counseling may also be warranted.
7. Prevention
Effective barrier contraception, safe sexual health, and age-appropriate vaccinations are important factors in
preventing HPV-related CC. Currently, a 9-valent vaccine extends the protection offered by the first approved US
quadrivalent HPV vaccine, to HPV-31, -33, -45, -52, and -58, as well as -6, -11, -16 and -18. Vaccines against HPV-16
and 18 can protect against more than 70% of CCs. The presence of protein from the 5 additional high-risk HPV
subtypes in the 9-valent vaccine may confer protection against 14% of HPV-associated cancers in females and 4%
of HPV-associated cancers in men. Extending HPV vaccination programs to males are now being discussed.
Sources
1. World Health Organization (Globocan
Fact Sheet): Cervical Cancer. Estimated Incidence, Mortality and Prevalence
Worldwide in 2012. 2015; http://globocan.iarc.fr/old/FactSheets/cancers/cervix-
new.asp.
2. World Health Organization. Human
papillomavirus (HPV) and cervical cancer. 2016;
http://www.who.int/mediacentre/factsheets/fs380/en/. Accessed May, 2017.
3. Epocrates (An Athenahealth
company). Cervical Cancer. 2017;
https://online.epocrates.com/diseases/25911/Cervical-cancer/Key-Highlights.
Accessed May, 2017.
4. US National Insitutes of Health.
National Cancer Institute. Cancer Stat Facts: Cervix Uteri Cancer. 2017;
https://seer.cancer.gov/statfacts/html/cervix.html. Accessed May, 2017.