Human papillomavirus: find out and try to prevent it

Human papillomavirus (HPV) is one of the most common infectious agents affecting the anogenital tract and mucosal surfaces. Because most infections are transient and asymptomatic, HPV is frequently underrecognized, yet persistent infection with certain HPV types is a necessary cause of cervical cancer and contributes to other anogenital and oropharyngeal cancers. This article reviews HPV virology and classification, clinical manifestations, diagnostic and screening strategies, treatment and follow‑up, vaccination and prevention, and relevant considerations for pregnancy and immunocompromised patients. Sources include guidance from the American College of Obstetricians and Gynecologists (ACOG), the National Institutes of Health (NIH), the Mayo Clinic, and the Cleveland Clinic.

What is human papillomavirus?

Human papillomavirus (HPV) is a group of more than 100 related DNA viruses that infect epithelial cells of the skin and mucosa. Different HPV types have different biological behaviors and clinical consequences. Clinically relevant types are commonly grouped into:

  • Low‑risk HPV types (for example, types 6 and 11): typically associated with benign lesions such as anogenital warts and low‑grade epithelial abnormalities.
  • High‑risk (oncogenic) HPV types (for example, types 16, 18, 31, 33, 45, 52, 58): associated with the development of high‑grade precancerous lesions and invasive cancers, particularly cervical cancer, but also anal, vulvar, penile, vaginal and oropharyngeal cancers. (ACOG; NIH)

Transmission occurs primarily through intimate skin‑to‑skin or mucosal contact. Because many infections are acquired soon after the onset of sexual activity and may be clinically silent, HPV is considered highly prevalent in sexually active populations. For most immunocompetent individuals, the host immune response clears the infection within months to a few years. However, when infection persists—especially with high‑risk types—there is a risk of progression to precancerous lesions and, over years to decades, invasive cancer. (NIH; Mayo Clinic)

Epidemiology and public health impact

HPV is extremely common. Most sexually active individuals will acquire at least one type of HPV infection in their lifetime. Exact prevalence estimates vary by population and testing methods, but high‑risk HPV prevalence and persistence are greatest in younger age groups, with a second, smaller peak in some populations later in life.

Globally, persistent infection with high‑risk HPV types is responsible for nearly all cases of cervical cancer, which remains a leading cause of cancer morbidity and mortality in regions with limited screening and vaccination coverage. In high‑resource settings, organized screening programs and vaccination have substantially reduced the incidence of cervical precancers and cancers. HPV is also implicated in increasing proportions of oropharyngeal cancers, especially in men, and in a subset of anal and other anogenital cancers. (NIH; ACOG)

Clinical manifestations

HPV infection can produce distinct clinical presentations or remain asymptomatic:

  • Anogenital warts (condylomata acuminata): Typically caused by low‑risk types such as HPV 6 and 11. Warts may be soft, fleshy growths on the vulva, vagina, cervix, perineum, perianal area or penis. They may be single or multiple and can vary in size. Warts themselves do not lead to cancer but can cause discomfort, pruritus, bleeding with trauma, and psychological distress. (Mayo Clinic; Cleveland Clinic)
  • Cervical epithelial abnormalities: Persistent infection with high‑risk types can cause cellular changes in the cervix detected by cytology (Pap test) or HPV testing. These changes are graded as low‑grade squamous intraepithelial lesion (LSIL/CIN1), which often regress, or high‑grade squamous intraepithelial lesion (HSIL/CIN2–3), which have a higher risk of progression to invasive cancer without treatment. (ACOG)
  • Other mucosal lesions and cancers: Persistent infection with high‑risk HPV types can lead to precancer and cancer of the vulva, vagina, anus, penis and oropharynx. HPV‑related oropharyngeal cancers commonly present as a unilateral neck mass or throat symptoms, often without prior mucosal lesions. (NIH; Mayo Clinic)
  • Subclinical infection: Most infections are asymptomatic and detected only by screening tests or incidentally.

Incubation periods vary considerably: initial infection may be followed by apparent clearance or may persist subclinically for months to years before clinical detection or progression. This long natural history is the basis for effective screening and prevention strategies. (ACOG; NIH)

Diagnosis and screening

Timely detection of cervical precancer is central to preventing invasive cervical cancer. Two principal laboratory modalities are used: cytology (Pap test) and molecular HPV testing.

Cervical cytology (Pap test)

  • Recommended to begin at age 21 regardless of sexual activity history.
  • For women aged 21–29 years: cervical cytology alone every 3 years is the preferred approach. HPV testing is not recommended for routine screening in this age group because of the high prevalence of transient infections. (ACOG)

HPV testing and co‑testing

  • For those aged 30–65 years there are three acceptable screening options:
  • Primary HPV testing alone every 5 years (preferred by many organizations),
  • Co‑testing (HPV test plus Pap cytology) every 5 years,
  • Pap cytology alone every 3 years.
  • Primary HPV testing can detect high‑risk HPV infection before cytologic abnormalities develop, enabling earlier identification of risk for precancerous changes. Genotyping for HPV 16 and 18 can stratify immediate risk, as these types carry the highest oncogenic potential. (ACOG; NIH)

Management of abnormal screening

  • Low‑grade cytologic abnormalities (e.g., LSIL) are often managed conservatively with repeat testing because many lesions regress spontaneously.
  • High‑grade cytology (HSIL) or persistent high‑risk HPV (especially with HPV 16/18) usually prompt referral to colposcopy and directed biopsy to evaluate for CIN2 or CIN3.
  • Confirmed high‑grade lesions (CIN2–3) typically require treatment to prevent progression to invasive cancer. (ACOG; ASCCP guidance summarized by ACOG)

Screening after treatment

  • After treatment of CIN2 or CIN3, surveillance protocols include HPV testing and/or cytology at defined intervals (for example, co‑testing at 12 and 24 months) to document clearance. Continued close follow‑up is important because treated patients remain at increased risk for recurrent disease. (ACOG)

Diagnostic tests beyond screening

  • Colposcopy and directed biopsy: indicated when screening results suggest high‑grade disease or persistent abnormalities. Colposcopy allows visualization under magnification and targeted biopsy of suspicious areas.
  • Histopathology of biopsy specimens determines grade (CIN1, CIN2, CIN3) and presence or absence of invasion.
  • HPV DNA testing with genotyping can identify high‑risk types; type 16 and 18 genotyping is often used to prioritize management decisions. (ACOG; NIH)

Treatment and management

Management is individualized based on lesion type, severity, patient age, reproductive plans and comorbidities.

Management of anogenital warts

  • Treatment is typically directed at removing warts to relieve symptoms and reduce lesion size. Options include:
  • Provider‑applied therapies: cryotherapy (liquid nitrogen or cryoprobe), surgical removal, electrocautery or laser ablation.
  • Patient‑applied topical agents for external warts: imiquimod cream, podofilox solution/gel, or other keratolytic agents. These agents stimulate local immune response or have cytotoxic action and require careful instruction and follow‑up. (Mayo Clinic; Cleveland Clinic)
  • Warts may recur despite treatment because treatment removes visible lesions but does not eradicate underlying HPV infection.
  • Treatment selection considers wart size, location, pregnancy status and patient ability to adhere to topical therapy. Cryotherapy is a common office‑based option. (Mayo Clinic)

Management of cervical intraepithelial neoplasia (CIN)

  • CIN1 (low‑grade): Often observed with repeat cytology and/or HPV testing because most regress spontaneously, especially in younger women. Observation includes repeat testing at intervals recommended by clinical guidelines. (ACOG)
  • CIN2: For nonpregnant patients, treatment is commonly recommended for those who have completed childbearing. Younger patients (for example, ages <25) may be considered for observation because of higher regression rates, but decisions should be individualized. (ACOG)
  • CIN3: Generally treated due to higher risk of progression to invasive cancer.

Treatment modalities for CIN2–3:

  • Excisional procedures:
  • Loop electrosurgical excision procedure (LEEP/LEEP cone): removes the transformation zone and abnormal tissue; it is the most commonly used excisional technique.
  • Cold knife conization: may be used when a larger or deeper specimen is needed, or when margins need to be carefully assessed.
  • Ablative procedures (e.g., cryotherapy or laser ablation): destroy abnormal tissue and are options when the lesion is fully visible and extension is limited.
  • Choice of procedure considers lesion characteristics and reproductive desires. Excisional procedures yield a tissue specimen for histology and margin assessment, which is advantageous when invasive disease is a concern. (ACOG)

Complications and fertility considerations:

  • Excisional treatments are associated with a small increased risk of adverse obstetric outcomes (e.g., preterm birth) when deep or repeated excisions are performed. This risk should be included in counseling about treatment options in individuals who desire future fertility. (ACOG)

Management in pregnancy

  • Visible anogenital warts may be observed during pregnancy because they can enlarge due to hormonal and immunologic changes. Treatment may be pursued if symptoms are substantial; cryotherapy is often used because it is well tolerated. Some topical agents are not recommended in pregnancy.
  • For cervical abnormalities, colposcopy is safe in pregnancy when indicated. Biopsy may be required if invasive disease is suspected. Definitive excisional treatment is generally deferred until postpartum unless invasive disease is strongly suspected. (ACOG; Mayo Clinic)

Management in immunocompromised patients

  • Individuals with immunosuppression (e.g., HIV infection, organ transplant recipients) have higher rates of persistent HPV infection, more extensive disease, and higher risk of progression to high‑grade lesions and cancer. They require more intensive surveillance and often earlier and more aggressive management. (NIH; ACOG)

Vaccination: the cornerstone of primary prevention

HPV vaccination prevents infection with the most common cancer‑causing and wart‑causing HPV types and is the most effective strategy to reduce future burden of HPV‑related disease.

Vaccines available

  • Nonavalent HPV vaccine (commonly used today in many countries): protects against HPV types 6, 11, 16, 18, 31, 33, 45, 52 and 58 (often referred to as Gardasil 9).
  • Earlier formulations (bivalent and quadrivalent vaccines) targeted subsets of these types; many regions now use the nonavalent vaccine because of its broader coverage.

Recommended age and dosing

  • Routine vaccination is recommended starting at ages 11–12 years; vaccination can begin as early as age 9.
  • Two‑dose series: For individuals initiating the series before age 15, a two‑dose schedule is recommended (doses separated by 6–12 months).
  • Three‑dose series: For those initiating vaccination at age 15 or older, or for immunocompromised individuals, a three‑dose schedule is indicated (doses at 0, 1–2 and 6 months).
  • Catch‑up vaccination is recommended through age 26 for those who were not adequately vaccinated earlier.
  • For adults aged 27–45, vaccination may be offered based on shared clinical decision‑making because many in this age group have already been exposed to HPV, though they may still benefit if they are not previously exposed to vaccine types. (ACOG; NIH)

Efficacy and safety

  • Vaccination is highly effective at preventing infection with vaccine‑targeted HPV types and the precancerous lesions associated with those types, especially when given prior to HPV exposure.
  • Safety data from large trials and post‑licensure surveillance demonstrate that HPV vaccines are well tolerated; common adverse effects include injection site reactions and transient systemic symptoms (fever, myalgia). Syncope can occur after any vaccination, so post‑vaccination observation is recommended. Severe allergic reactions are rare. (ACOG; CDC summarized by NIH)

Vaccination after treatment or in persons with prior HPV infection

  • Vaccination does not treat existing HPV‑related disease, but it may protect against subsequent infection with other vaccine‑covered types. Individuals who have had treatment for precancerous lesions are still recommended to complete vaccination according to age‑based recommendations. (ACOG; NIH)

Prevention beyond vaccination

  • Condom use reduces the risk of HPV transmission and associated disease but does not eliminate it entirely because HPV can infect areas not covered by a condom. Consistent condom use is still recommended to reduce transmission of HPV and other sexually transmitted infections. (Mayo Clinic; Cleveland Clinic)
  • Smoking cessation: Tobacco smoking is associated with increased risk of persistent HPV infection and progression to cervical precancer and cancer. Smoking cessation is an important modifiable risk factor. (NIH)
  • Limiting the number of sexual partners and delaying onset of sexual activity can reduce the likelihood of early HPV exposure, but vaccination remains the most effective population‑level preventive measure.
  • Screening adherence: Even vaccinated individuals should follow routine cervical cancer screening recommendations, as vaccines do not cover all oncogenic HPV types and prior vaccination does not obviate the need for screening. (ACOG)

Follow‑up and long‑term considerations

  • Persistence of high‑risk HPV infection is the key determinant of progression to high‑grade lesions. Surveillance after treatment for CIN2/3 involves periodic HPV testing and cytology to detect recurrence early.
  • Invasive disease detected on biopsy requires multidisciplinary management and staging, with treatment tailored to extent and site of disease.
  • Counseling on recurrence risk, expected surveillance intervals and implications for future pregnancy or fertility is integral to care.

Special populations

  • Adolescents and young adults: Given high rates of transient infection and high vaccine effectiveness when given before HPV exposure, vaccination programs targeting preadolescents are a public health priority.
  • Men: While screening programs for asymptomatic men are not routinely performed, vaccination in boys and men reduces transmission and prevents HPV‑associated anogenital and oropharyngeal disease. Men who have sex with men and immunocompromised men benefit particularly from vaccination and, in some settings, anal cancer screening may be considered. (NIH; Cleveland Clinic)
  • Immunocompromised persons: Require individualized monitoring and often more aggressive treatment and surveillance due to increased risk of persistent infection and progression. (NIH; ACOG)

Psychological and social considerations

A diagnosis of HPV infection or detection of cervical abnormalities can provoke anxiety and stigma. Clinicians should provide clear education that HPV is common, that most infections are cleared by the immune system, and that detection of HPV or low‑grade abnormalities does not imply personal failure. Counseling should include discussion of implications for partners, prevention strategies, and the rationale for recommended follow‑up and treatment. Partner notification is generally not required for HPV in the same way as for other reportable sexually transmitted infections, but patients may wish to discuss prevention measures with partners. (Mayo Clinic; Cleveland Clinic)

Emerging issues and research

  • Implementation of primary HPV testing and HPV‑based screening protocols is expanding. Molecular assays and risk‑based algorithms continue to evolve to improve specificity and reduce unnecessary procedures.
  • Continued surveillance of vaccine impact has shown reductions in vaccine‑type infections and genital warts in populations with high coverage. Ongoing research evaluates the long‑term durability of vaccine protection, optimal schedules, and the impact on HPV‑associated cancers.
  • Strategies for anal cancer screening in high‑risk populations, and for tailored vaccination strategies in older age groups, are areas of active investigation. (NIH; ACOG)

Key takeaways

  • HPV is a common virus transmitted primarily by intimate contact. Most infections are transient and asymptomatic, but persistent infection with high‑risk types can cause cervical and other anogenital and oropharyngeal cancers. (NIH; ACOG)
  • Routine cervical screening with cytology and/or HPV testing detects precancerous lesions early, enabling effective treatment before invasive cancer develops. Screening guidelines vary by age; initiation at age 21 is standard for cytology. (ACOG)
  • Treatment for visible warts and for precancerous cervical lesions is effective. Management choices depend on lesion severity, patient age and reproductive plans. (Mayo Clinic; Cleveland Clinic; ACOG)
  • HPV vaccination is safe and highly effective at preventing infection with the most common oncogenic and wart‑causing HPV types; routine vaccination is recommended in early adolescence, with catch‑up through age 26 and individualized decision‑making for some adults up to age 45. Vaccination does not replace the need for cervical screening. (ACOG; NIH)
  • Prevention strategies include vaccination, consistent condom use, smoking cessation, and adherence to screening recommendations. Special populations such as pregnant individuals, immunocompromised persons and men who have sex with men require individualized counseling and care. (ACOG; Mayo Clinic; Cleveland Clinic)

For detailed clinical practice guidance, refer to ACOG committee opinions and practice bulletins on HPV and cervical cancer screening and management, the NIH/NCI resources on HPV and cancer, and patient resources from the Mayo Clinic and Cleveland Clinic. These organizations provide evidence‑based, up‑to‑date information for clinicians and patients on prevention, screening and treatment of HPV‑related disease. (ACOG; NIH; Mayo Clinic; Cleveland Clinic)