Human Papillomavirus (HPV): Comprehensive Overview
What is HPV?
HPV is the most common sexually transmitted infection in the United States, with an estimated 6.2 million new infections annually, caused by over 100 viral types that infect mucosal and cutaneous membranes of the anogenital and upper aerodigestive tract regions. 1, 2
Viral Classification and Disease Associations
Low-risk HPV types (primarily types 6 and 11) cause approximately 90% of genital warts, benign cervical cell changes, and recurrent respiratory papillomatosis 1
High-risk oncogenic types (including 16,18,31,33,35,39,45,51,52,56,58,59,68,69,73, and 82) are detected in 99% of cervical cancers, with types 16 and 18 alone responsible for approximately 70% of cervical cancers worldwide 1
HPV infection is associated with multiple cancer types: cervical, vulvar, vaginal, penile, anal, and oropharyngeal cancers 1
Natural History and Epidemiology
Nearly 90% of HPV infections are transient and resolve spontaneously within 1-2 years without clinical sequelae 1
Persistence occurs in approximately 10% of infected healthy women, with only 1% developing neoplastic HPV-related lesions 1
The highest prevalence occurs in sexually active adolescents and young adults, with most acquiring HPV shortly after becoming sexually active 1, 3
In men, HPV infection duration and persistence are shorter than in women 1
Globally, there are approximately 30.9 million cases of cervical precancerous lesions, 32 million cases of genital warts, and 630,000 cases of HPV-related cancers diagnosed annually 1
Prevention Strategies
Primary Prevention: Vaccination
Routine HPV vaccination is recommended for all females and males at age 11-12 years (can start as early as age 9), with catch-up vaccination for females through age 26 and males through age 21 (through age 26 for men who have sex with men and immunocompromised persons). 2
Available Vaccines
Bivalent vaccine: Contains VLPs of HPV types 16 and 18 1
Quadrivalent vaccine (4vHPV): Contains VLPs of types 6,11,16, and 18 1
Nonavalent vaccine (9vHPV): Contains VLPs of types 6,11,16,18,31,33,45,52, and 58, potentially preventing approximately 90% of cervical and other HPV-related cancers 2, 4
Vaccination Schedule and Administration
Standard schedule: 3-dose series administered intramuscularly at 0,2, and 6 months 1
Two-dose schedules have shown no difference in seroconversion compared to three-dose schedules, though single-dose schedules remain controversial 4
The vaccine is most effective when administered before sexual activity begins, as it does not protect against HPV types with which individuals are already infected at the time of vaccination 1, 2
Females infected with one or more vaccine HPV types before vaccination would still be protected against disease caused by the other vaccine HPV types 1
Vaccine Efficacy and Real-World Impact
Clinical trials demonstrate high efficacy in preventing persistent HPV infection, cervical cancer precursor lesions, vaginal and vulvar cancer precursor lesions, and genital warts caused by vaccine HPV types among previously uninfected females 1
From the prevaccine era to 2015-2018, 4vHPV-type prevalence decreased 88% among females aged 14-19 years and 81% among those aged 20-24 years 5
Significant declines among unvaccinated females (87% among those aged 14-19 years, 65% among those aged 20-24 years) demonstrate herd protection effects 5
The vaccine is highly effective against oral HPV types 16/18 infection, with significant IgG antibody development in oral fluid post-vaccination 4
Special Populations Requiring Vaccination
Three doses of HPV vaccine are recommended for high-risk populations aged 9-26 years, including: 1, 2
- HIV-infected patients
- Men who have sex with men (MSM)
- Transgender persons
- Patients with primary or secondary immunocompromising conditions
- Inflammatory bowel disease patients
- Solid organ or hematopoietic stem cell transplant recipients
- Patients receiving immunosuppressive or biological treatment
- Patients with recurrent respiratory papillomatosis
- Children with a history of sexual abuse
Behavioral Prevention
Abstaining from sexual activity is the surest way to prevent genital HPV infection 1, 2
For sexually active individuals, a monogamous relationship with an uninfected partner is the strategy most likely to prevent future infections 1, 2
Consistent and correct condom use reduces HPV acquisition risk by approximately 70% among newly sexually active individuals 1, 2
Neither routine surveillance for HPV infection nor partner notification is useful for prevention, as the majority of partners are already infected 1, 2
Screening Recommendations
Cervical Cancer Screening
All women should have a Pap test for cervical cancer screening within 3 years of beginning sexual activity or by age 21 years, whichever occurs first. 1, 2
Age-Specific Screening Protocols
Women aged <30 years: Annual screening recommended 1
Women aged ≥30 years with three normal consecutive Pap tests: Screen every 2-3 years 1, 2
Women aged ≥30 years with both negative Pap and HPV testing: Screening interval can be extended to 3 years 2
HPV Testing Adjuncts
HPV DNA testing (HC2 High Risk test) is recommended as an adjunct to regular Pap screening in women aged >30 years 1
HPV DNA testing should be used to triage women with equivocal ASC-US Pap test results 1
High-Risk Population Screening
Data are insufficient to recommend routine anal cancer screening with anal cytology in persons living with HIV/AIDS or HIV-negative MSM 2
An annual digital anorectal examination may be useful for early detection of anal cancer in high-risk populations 2
If anal cytologic screening indicates abnormal findings, high-resolution anoscopy should be performed with biopsy of abnormal areas 2
Treatment of HPV-Related Conditions
Important Caveat
HPV infections themselves are not treated; treatment is directed only at HPV-associated lesions. 1
Treatment Modalities for Precancerous Lesions
Treatment options for cervical, vaginal, and vulvar cancer precursors include local approaches that remove the lesion: 1, 2
- Cryotherapy
- Electrocautery
- Laser therapy
- Surgical excision
Genital Warts Treatment
Topical pharmacologic agents are used for genital warts 1
Imiquimod 3.75% cream is recommended for anogenital warts treatment 2
Available therapies might reduce but probably do not eliminate infectiousness 1
Recurrent Respiratory Papillomatosis
JORRP (juvenile-onset recurrent respiratory papillomatosis) results from vertical transmission during delivery, with median diagnosis age of 4 years 1
The clinical course is variable but associated with extensive morbidity, requiring a median of 13 lifetime surgeries to remove warts and maintain an open airway 1
Patient Counseling and Education
Essential Counseling Points
HPV vaccination does not protect against persistent infection or disease caused by HPV types with which individuals are already infected at the time of vaccination 2
Vaccination is not a substitute for routine cervical cancer screening; vaccinated females should continue screening as recommended 1
When HPV testing is performed, it should be accompanied by evidence-driven and patient-centered counseling to minimize negative psychosocial outcomes 2
Educational Focus Areas
Education should address illness, treatment, symptom burden, and sexual behaviors associated with increased HPV transmission risk 2
Counseling for emotional support can be provided through enhanced coping techniques and delivering resources and information 2
Smoking has been linked with increased prevalence of oral HPV infection and is associated with worse prognosis 2
Special Considerations for HIV-Infected Individuals
HPV vaccination is recommended for all HIV-infected males and females in a 3-dose series at 11 or 12 years of age, and for those 13-26 years of age if not previously vaccinated 2
HIV-infected MSM with HPV infection are at increased risk for anal dysplasia and cancer 2
Evidence regarding the efficacy and risk of HPV vaccination in the context of HIV infection remains limited 4
Common Pitfalls to Avoid
Do not assume vaccination eliminates the need for cervical cancer screening - screening remains essential even in vaccinated individuals 1, 2
Do not perform routine partner notification or surveillance - HPV is so prevalent that most partners are already infected, and no prevention strategies exist for partners 1, 2
Do not delay vaccination waiting for "ideal" timing - even sexually active individuals benefit from vaccination against HPV types they have not yet encountered 1
Do not misinterpret vaccine effectiveness data - long-term cancer prevention outcomes require decades of follow-up as vaccinated cohorts reach peak cancer incidence ages 6