Human Papillomavirus: Screening, Testing, and Prevention


With more than 200 types identified, human papillomavirus (HPV) commonly causes infections of the skin and mucosa. HPV infection is the most common sexually transmitted infection in the United States. Although most HPV infections are transient and subclinical, some lead to clinical manifestations ranging from benign papillomas or warts to intraepithelial lesions. In some patients, persistent infection with high-risk mucosal types, especially HPV-16 and HPV-18, causes anal, cervical, oropharyngeal, penile, vaginal, and vulvar cancers. Most HPV-related cancers are believed to be caused by sexual spread of the virus. A history of multiple sex partners; initiation of sexual activity at an early age; not using barrier protection; other sexually transmitted infections, including HIV; an immunocompromised state; alcohol use; and smoking have been identified as risk factors for persistent HPV infections. Screening for HPV infection is effective in identifying precancerous lesions and allows for interventions that can prevent the development of cancer. Use of condoms and dental dams may decrease spread of the virus. Vaccination is the primary method of prevention. The nonavalent HPV vaccine is effective in preventing the development of high-grade precancerous cervical lesions in noninfected patients. Vaccination is ideally administered at 11 or 12 years of age, irrespective of the patient's sex. In general, a two-dose series is recommended if administered before 15 years of age; however, individuals who are immunocompromised require three doses.

There are more than 200 types of human papillomavirus (HPV), a DNA virus that infects cutaneous and mucosal epithelial cells. HPV is spread by direct skin-to-skin contact and has tropisms for cutaneous or mucosal epithelial cells.1 A small subset of HPV types can cause cutaneous warts.2 The approximately 40 types that infect mucosal surfaces are typically spread through sexual contact, including vaginal, anal, or oral sex, and can be divided into low-risk and high-risk types based on their associated cancer risk. Low-risk types cause warts, whereas the 15 high-risk types cause cervical intraepithelial neoplasia (CIN) and squamous cell carcinomas of the anogenital tract and oropharyngeal mucosa.3,4 Vertical or horizontal spread of HPV can occur during the perinatal period and is associated with oral infections and respiratory papillomatosis.5,6 Concomitant cervical and anal infections have been demonstrated in women without a history of anal intercourse and may be a result of autoinoculation.7


Human Papillomavirus

Vaccination has been demonstrated to reduce the prevalence of vaccine-type HPV in females, anogenital warts, and precancerous cervical lesions.

According to a 2018 Cochrane review, vaccinating women, with or without HPV exposure, between 15 and 26 years of age decreases the risk of cervical intraepithelial neoplasia 2 and 3, with a number needed to treat of 39.

On June 12, 2020, the U.S. Food and Drug Administration approved adding the prevention of head and neck cancers caused by HPV as an indication for the nonavalent HPV vaccine (Gardasil 9).

HPV = human papillomavirus.

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Clinical recommendationEvidence ratingComments

Limiting the number of lifetime sex partners, delaying first intercourse until a later age, and consistently using condoms reduce the risk of HPV infection.13,14


Mixed-quality randomized controlled trials of disease-oriented outcomes

Smoking and alcohol cessation should be recommended to reduce the risk of HPV persistence and the development of HPV-related malignancies.15,16


Two case-control studies

Vaccination should be recommended to prevent the development of high-grade precancerous cervical lesions in women.57,63,64


Consistent findings from a Cochrane review of randomized controlled trials of disease-oriented outcomes; evidence-based practice guideline

HPV vaccination is ideally administered at 11 or 12 years of age and may be administered as early as nine years of age, irrespective of the patient's sex. In immunocompetent individuals immunized before 15 years of age, a two-dose series is indicated. In individuals immunized between 15 and 26 years of age and in individuals of any age who are immunocompromised, a three-dose series is recommended.57,62


Evidence-based practice guidelines

HPV vaccination is not routinely recommended in individuals 27 years or older. Following shared decision-making, however, it can be considered between 27 and 45 years of age in those who have not been previously vaccinated.57


Evidence-based practice guideline

In patients 21 to 29 years of age, cervical cancer screening should be performed every three years using cervical cytology alone. In patients 30 to 65 years of age, cervical cancer screening should be performed every three years using cervical cytology alone,

The Author

JEFFREY D. QUINLAN, MD, FAAFP, is a professor in and chair of the Department of Family Medicine at the University of Iowa Carver College of Medicine, Iowa City. At the time this article was written, he was a professor in and chair of the Department of Family Medicine at the Uniformed Services University of the Health Sciences, Bethesda, Md.

Address correspondence to Jeffrey D. Quinlan, MD, FAAFP, Roy J. and Lucille Carver College of Medicine, University of Iowa, 01286D PFP, 200 Hawkins Dr. Iowa City, IA 52242 (email: Reprints are not available from the author.

Author disclosure: No relevant financial affiliations.


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