Am Fam Physician. 2021;104(2):152-159
Patient information: A handout on this topic is available at https://familydoctor.org/condition/human-papillomavirus-hpv.
Author disclosure: No relevant financial affiliations.
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
WHAT'S NEW ON THIS TOPIC
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.
| Recommendation | Sponsoring organization |
|---|---|
| Do not perform cervical cytology (Pap test) or HPV screening in immunocompetent women younger than 21 years. | American Society for Colposcopy and Cervical Pathology |
| Do not perform annual cervical cytology (Pap test) or annual HPV screening in immunocompetent women with a history of negative screening. | American Society for Colposcopy and Cervical Pathology |
| Do not perform low-risk HPV testing. | American Society for Clinical Pathology |
Epidemiology and Prevalence
The Centers for Disease Control and Prevention reports that 79 million Americans are infected with HPV and an additional 14 million are newly infected each year.3 Data from early HPV vaccine trials suggest that the lifetime prevalence of the infection is 85% in women and 91% in men who have had at least one sex partner.8
The prevalence of cutaneous warts is highest in school-aged children (up to 30%), then declines with advancing age.2 HPV infection is the most common sexually transmitted infection in the United States. Genital warts occur in 1% of sexually active adults.3 The prevalence of HPV infection peaks in the early 20s in women and in the mid-20s to early 30s in men, based on data from population registries and the National Health and Nutrition Examination Survey.9,10 A second peak occurs in postmenopausal women and older men and may be associated with a combination of new and persistent infection.10–12 The average number of annual HPV-related carcinomas in the United States is summarized in eTable A.
| Location | Female | Male | Total |
|---|---|---|---|
| Anus | 4,751 | 2,332 | 7,083 |
| Cervix | 12,143 | — | 12,143 |
| Oropharynx | 3,530 | 16,245 | 19,775 |
| Penis | — | 1,348 | 1,348 |
| Vagina | 867 | — | 867 |
| Vulva | 4,114 | — | 4,114 |
| Total | 25,405 | 19,925 | 45,330 |
Risk Factors
INFECTION
PERSISTENCE
Persistent oral and genital HPV infections are associated with alcohol use and smoking.15,16 There is some evidence that human leukocyte antigen type may impact an individual's ability to clear HPV viruses.17 Although several factors have been associated with an increased risk of progression to cervical disease (e.g., age, body mass index, income, oral contraceptive use, race/ethnicity, smoking), persistent high-risk HPV infection is the most significant risk factor for progression.18,19
Pathogenesis and Subtypes
Infection with a low-risk HPV type does not preclude infection with a concomitant high-risk type. One study demonstrated that 31% of genital warts contain both low- and high-risk types of HPV.20
Subscribe
From $145- Immediate, unlimited access to all AFP content
- More than 130 CME credits/year
- AAFP app access
- Print delivery available
Issue Access
$59.95- Immediate, unlimited access to this issue's content
- CME credits
- AAFP app access
- Print delivery available
Article Only
$25.95- Immediate, unlimited access to just this article
- CME credits
- AAFP app access
- Print delivery available
