Human papillomavirus (HPV)

Michael Melia, M.D.


  • Non-enveloped DNA virus.
  • HPV is widespread worldwide.
  • >100 types recognized as capable of causing human infection with specific clinical manifestations.
  • Papillomaviruses use skin or mucosal linings (such as oral, genital, anal or respiratory) to replicate.
  • Some types have oncogenic potential.


  • The most common sexually transmitted infection in the U.S.
  • Most infections are asymptomatic and resolve spontaneously within 2 years.
  • Anogenital warts (condylomata acuminatum): see separate module on anogenital warts.
  • Uterine cervical infection without visible warts:
    • Usually no clinical signs of infection.
    • While "high risk" (oncogenic) virus types are responsible for 99.7% of all cervical cancer, most infections do not lead to cervical cancer.
    • Liquid-based cytology (e.g., ThinPrep®) and conventional Pap smears are both acceptable for cervical cancer cytology.
      • Liquid-based cytology permits co-testing for HPV, which may help guide the management of women whose Pap smear reveals ASCUS or LSIL, as well as women ≥30y with normal Pap smears.
    • Cervical cancer screening may be undertaken by primary HPV testing every 5y (preferred by the American Cancer Society, with screening beginning at 25y through 65y), co-testing (Pap + HPV testing) every 5y, or Pap test every 3y.
      • USPSTF recommends Pap test q3y for women 21-29y, with one of the above three methods for women 30-65y.
  • Perianal and intra-anal HPV infection without visible warts:
    • Oncogenic HPV types account for most anal intraepithelial neoplasia (AIN) cases and squamous cell carcinoma of the anorectal area.
    • The cellular transition zone of the anal verge is at higher risk of infection than other mucosal surfaces in the perirectal area.
    • Consideration of screening high-risk groups (e.g., MSM, people with HIV) for anal neoplasia using anal Pap smears is recommended by expert panels (CDC, American Society of Colon and Rectal Surgeons).
      • These recommendations are strengthened by the results of the ANCHOR study showing a lower risk of incident anal cancer among persons with anal HSIL. They receive treatment as compared with active monitoring.
    • Provided access to appropriate follow-up is available, the HIV Medicine Association of the Infectious Diseases Society of America recommends anal Pap smears for all HIV-infected MSM, HIV-infected women with a history of receptive anal intercourse and/or an abnormal cervical Pap smear, and all HIV-infected patients with genital warts
  • Cutaneous warts: common, plantar, flat
    • Primarily seen in children/adolescents but may be an occupational hazard in butchers, fish handlers and meat packers.
    • Caused by non-oncogenic HPV types (HPV-1, -2, -4, -27, and -57 most commonly).
    • Usually asymptomatic except at weight-bearing or frequent friction sites.
    • Spontaneous resolution of 50-90% within 1-5 years.
    • Patients with warts lasting >18 months despite treatment are more likely to be HLA-type DQA1*0301.
    • Common warts (verruca vulgaris):
      • The most common type of cutaneous wart.
      • Most prevalent in young children.
      • Usually on the hands.
      • A typical lesion is a brown, exophytic, hyperkeratotic papule [Fig 1]
    • Plantar warts (verruca plantaris):
      • The second most common type of wart.
      • Most common in adolescents/young adults.
      • Upon paring down [Fig 2], thrombosed capillaries distinguish from callus.
    • Flat warts (verruca plana):
      • Most commonly seen in children.
      • Face [Fig 3], neck, chest, forearms, and legs flexor surfaces
  • Recurrent respiratory papillomatosis: HPV-driven disease primarily of the larynx.
    • Two forms:
      • Juvenile-onset: transmitted from HPV-infected mother during passage through the birth canal.
      • Adult-onset: believed to be an STD.
    • Detection usually follows complaints of voice changes or, in rapidly growing lesions, secondary to difficulty breathing.
    • Complications include obstructive, life-threatening respiratory compromise in infants/children.
    • The adult form is usually less aggressive than that seen in infants/children.
    • Caused by non-oncogenic HPV genotypes, most frequently HPV-6 and HPV-11.
  • Other uncommon forms:
    • Buschke-Lowenstein tumors (giant condylomas, GCBL)
      • Slow-growing verrucous lesions are highly destructive to contiguous tissue. Metastases are uncommon.
      • Most commonly located on the glans penis in (usually uncircumcised) men > other anogenital mucosal surfaces, including the vulva, vagina, rectum, scrotum, and bladder.
      • HPV suspected cause with types 6 and 11 commonly found and types 16 and 18 occasionally found; type 54 rarely found.
      • In the U.S., it accounts for 5-24% of penile cancers and 0.3-0.5% of all male malignancies.
      • Bladder lesions have been associated with schistosomiasis (e.g., Schistosoma haematobium).
      • Patients with suspect GCBL should be referred to dermatology for diagnosis and treatment.
    • Bowenoid papulosis
      • Flesh-colored to reddish papules outside the anogenital area.
      • HPV (usually type 16)-induced papules with distinctive histopathology (called Bowen’s disease when occurring outside the anogenital region and also seen in erythroplasia of Queyrat) of focal epidermal hyperplasia and dysplasia and evidence of squamous cell carcinoma (SCC) in situ.
      • No racial or gender preferences; were found in sexually active young adults with a mean age of 31 yrs.
    • Bowen’s disease (BD)
      • Gradually enlarging, well-demarcated, usually solitary [multiple in 10–20%] erythematous plaque with an irregular border and surface crusting or scaling, often of the lower leg (60-85% of cases).
      • It may occur at any age in adults but is rare before the age of 30 years (sixth and seventh decades most common).
      • Women account for up to 85% of cases.
      • Patients with suspect BD should be referred to a dermatologist for management.
      • HPV is suspected but not proven as the etiological agent of some or all of the cases.
    • Epidermodysplasia verruciformis
      • Rare, probably autosomal recessive (sex-linked also reported).
      • Disseminated (trunk, hands, upper and lower extremities, and face characteristic) flat to warty eruptions and reddish-brown pigmented plaques beginning early in life with frequent malignant transformation to squamous cell carcinomas (SCC) after age 30 years, first on sun-exposed areas.
      • Multiple HPV types often present simultaneously. HPV-5 and HPV-8 have been isolated in more than 90% of associated SCC.
      • Ddx includes SCC, common warts, flat warts, tinea versicolor, and benign papillomas.
      • Patients with the suspected disease should be referred to an oncologic dermatologist for definitive diagnosis and management.
    • Erythroplasia of Queyrat
      • Lesions on the glans penis (similar in morphology to Bowen’s disease lesions) have oncogenic potential.
      • Occur on the glans penis and under the prepuce, almost exclusively in uncircumcised men.
      • Histopathology is intraepithelial neoplasia.
      • HPV is suspected but not proven as the etiological agent of some or all of the cases.
      • Suspect cases should be referred to a dermatologist for management.


  • Cutaneous surfaces: plantar warts, common warts, flat warts; other rare manifestations noted above.
  • Mucosa: genitalia in areas of coital friction, perianal/anal area, mouth, cervix
  • Larynx/trachea: respiratory papillomatosis


External Anogenital Warts

Cutaneous Warts

  • 67% resolve spontaneously within 2 years among children; clearance among adults can be much slower, and warts can last 5-10 years.
  • Many remedies have been tried, including immunotherapy, surgical removal, and chemical or physical destruction.
  • In the 2012 Cochrane Review[15], only salicylic acid was found superior to placebo.
    • One study found that liquid nitrogen was superior to placebo (and salicylic acid) for hand warts.
  • Hand warts:
    • Self-application of topical salicylic acid (e.g., 17% or 27.5%) once or twice daily for up to 12 wks (cure rates range from 0% to >80%).
    • Cryotherapy (cure rates range 14% to >90%).
  • Plantar warts:
    • 40% salicylic acid plaster taped into place x48-72h followed by debridement (e.g., with a nail file or pumice stone). Repeat the cycle for a total duration of 2-3 weeks.
      • Avoid damaging surrounding skin when paring, given the risk of spread of infection.
    • Cryotherapy
    • Combination treatment may be undertaken but may also be associated with more side effects.
    • One small study in children showed that imiquimod 5% + salicylic acid 15% was superior to cryotherapy in eradicating plantar warts at 3 months.
  • Flat warts:
    • Tretinoin (retinoic acid cream 0.05%) 1-2x daily ± topical 5% benzoyl peroxide or topical 5% salicylic acid cream until cured. Sun protection is important.
    • Topical 5-fluorouracil cream (1% or 5%) twice daily until resolved. Sun protection is essential.
    • Imiquimod (5%) at bedtime
    • Cryotherapy
    • Isotretinoin 30 mg/d was shown to eradicate treatment-refractory facial flat warts in a small study of adults.
  • Filiform warts: snipping or curettage
  • For treatment-refractory warts: Dermatology consultation for consideration of alternative therapy, including topical immunotherapy or intralesional bleomycin.

Referral for Management

  • Cervical warts
  • Rectal mucosal warts
  • Oral warts
  • Suspected laryngeal involvement.
  • Suspected cancerous lesions
  • Epidermodysplasia verruciformis
  • Bowen’s disease and Bowenoid papulosis
  • Buschke-Lowenstein tumors
  • Erythroplasia of Queyrat

Vaccines (Prevention)

  • Vaccination: see the HPV vaccine module for additional details.
    • 9-valent Gardasil9®
      • Protects against the two HPV types (16 and 18) responsible for the majority of cervical cancers, the two types responsible for the majority of anogenital warts (6 and 11), and also types 31, 33, 45, 52, and 58
        • These final five types are responsible for approximately 15% of cervical cancers.
      • Initially licensed in 2014, now licensed for females and males aged 9 through 45 years
  • Prevention strategy:
    • Ideally, the vaccine should be administered before the sexual debut.
    • Recommendations:
      • Vaccinate boys and girls aged 11-12 years.
      • May begin vaccine series as early as age 9 years.
      • Catch-up vaccination is recommended for all persons aged 13-26 years.
      • Shared decision-making is recommended for adults 27 through 45 years of age.
    • Co-administration with other age-appropriate vaccines is fine; the 9vHPV vaccine is not a live virus.
    • Dosing recommendations:
      • < 15 years: Two-dose series spaced by 6-12 months
        • The minimum interval between doses is 5 months.
      • ≥15 years and immunocompromised persons (cancer, HIV, immunosuppressive medications): Three-dose series at 0, 1-2, and 6 months
        • The minimum interval between first and second doses is 4 weeks.
        • The minimum interval between second and third doses is 12 weeks.
        • The minimum interval between first and third doses is 5 months.
      • If the vaccine series is interrupted, it does not need to be restarted.
  • Persons previously vaccinated with the 2vHPV or 4vHPV vaccine:
    • Females who began the vaccine series with the 2vHPV or 4vHPV vaccine may complete the vaccine series with the 9vHPV vaccine according to the dosing recommendations above.
    • Females who previously completed the 2vHPV or 4vHPV vaccine series may receive the 9vHPV vaccine series.
      • There is no recommendation for or against this practice.
      • Greater protection against the additional HPV types may result.
      • Shared decision-making should be undertaken regarding the potential benefit of immunity against the five additional oncogenic HPV strains covered by the 9-valent vaccine.
    • Additional relevant guidance from CDC is available here.
    • Bivalent Cervarix was never approved for use in males. Any such doses should not be counted as evidence of prior HPV vaccination.
  • Vaccination has no therapeutic effect on existing Pap test abnormalities, HPV infection or genital warts.
    • However, patients with these diagnoses should still be vaccinated, as they may not yet have been infected with all (or any) of the vaccine HPV types.
  • Lactating women can receive HPV vaccines.
  • HPV vaccination is not recommended in pregnancy.
    • Women who learn of pregnancy amid the vaccine series should be reassured that the vaccines are not causally associated with adverse pregnancy outcomes or events to the developing fetus. The fetal risk with the 9vHPV vaccine is minimal as the vaccine is a non-infectious subunit particle.
      • If a person is found to be pregnant after receipt of HPV vaccination, further doses should be deferred until completion of pregnancy.
    • Observational long-term follow-up data obtained from women who received bivalent HPV vaccination showed no risk of miscarriage for pregnancies conceived less than 90 days from vaccination.
      • Among pregnancies conceived at any time from bivalent HPV vaccination, exposure was not associated with an increased risk of miscarriage overall or in subgroups, except for miscarriages at weeks 13-20 of gestation (relative risk 1.35), suggesting a need for further study.
    • Exposure during pregnancy can be reported to Merck at 800-986-8999.
  • Contraindications: pregnancy; persons with a history of immediate hypersensitivity to any vaccine component (9vHPV vaccine contains a trace amount of yeast protein).
  • Cervical cancer screening in vaccinated women: Cervical cancer screening recommendations have not changed for female patients who receive the HPV vaccines.
  • Impact:
    • HPV vaccination has lowered HPV prevalence by 81% (females aged 20-24y) and 88% (females aged 14-19y) compared with the pre-vaccine era
    • The impact on 4vHPV-type prevalence was 85% overall in 2015-2018, including 90% among vaccinated females and 74% among unvaccinated females, highlighting a herd immunity benefit.

Selected Drug Comments




Enhances local immune response by stimulating the production of interferon and other cytokines. Local inflammatory reactions are common and range from mild to moderate. The patient should be so advised. Expense and duration of treatment are drawbacks to use. Some experts have recommended use in the treatment of anal intraepithelial neoplasia in HIV-positive men, but there have been no RCTs to test the efficacy of such treatment.


Resin is an antimitotic agent. Must apply a VERY THIN layer. Over-application or failure to dry the area can lead to local irritation.

TCA (trichloroacetic acid), BCA (bichloroacetic acid).

Caustic agents destroy warts by chemical coagulation of proteins. These agents have low viscosity compared to water. Therefore, they can spread rapidly if applied excessively. Hence, use sparingly and with care.

Bevacizumab (Avastin)

The case series indicates that this cancer drug (anti-vascular endothelial growth factor antibody) benefits the management of recurrent respiratory papillomatosis.

Nine-valent human papillomavirus vaccine (9vHPV)

Recommendations as above. Having genital warts is not a contraindication to vaccination as prevention of infection with the other types in the vaccine is still possible. Also, studies suggest that the titers against vaccine types are higher and possibly more long-lived than those following natural infection. The impact of the vaccine on the natural history of infection in patients with type-specific infection is not known and likely limited.


  • Subclinical genital HPV infection without exophytic warts: routine use of 3-5% acetic acid to identify these areas is not recommended. In the absence of coexistent SIL, treatment is not recommended.
  • Cervical cancer screening guidelines:
    • American Cancer Society primary HPV testing every 5y (preferred), co-testing (Pap + HPV testing) every 5y, or Pap test every 3y
      • Screen women 25y through 65y
    • The United States Preventative Services Task Force:
      • Pap test q3y for women 21-29y
      • Primary HPV testing every 5y, co-testing (Pap + HPV testing) every 5y, or Pap test every 3y for women 30-65y
    • Management of abnormal findings should be undertaken per consensus guidelines established in 2019 by the American Society for Colposcopy and Cervical Pathology.
      • Patients are assigned one of six clinical action thresholds that guide the next steps through these guidelines.
      • A management guidelines application is available here:
    • Stop screening at age 65 years (assuming adequate negative prior screening results)

Basis for recommendation

  1. Fontham ETH, Wolf AMD, Church TR, et al. Cervical cancer screening for individuals at average risk: 2020 guideline update from the American Cancer Society. CA Cancer J Clin. 2020;70(5):321-346.  [PMID:32729638]

    Comment: This updated document details the evidence in support of the cervical cancer screening guidelines summarized above.

  2. US Preventive Services Task Force, Curry SJ, Krist AH, et al. Screening for Cervical Cancer: US Preventive Services Task Force Recommendation Statement. JAMA. 2018;320(7):674-686.  [PMID:30140884]

    Comment: This updated document details the evidence in support of the cervical cancer screening guidelines summarized above.

  3. Meites E, Kempe A, Markowitz LE. Use of a 2-Dose Schedule for Human Papillomavirus Vaccination - Updated Recommendations of the Advisory Committee on Immunization Practices. MMWR Morb Mortal Wkly Rep. 2016;65(49):1405-1408.  [PMID:27977643]

    Comment: This 2016 report provides further detail regarding the revised HPV vaccine recommendations, including the use only of the 9vHPV vaccine.


  1. Rosenblum HG, Lewis RM, Gargano JW, et al. Human Papillomavirus Vaccine Impact and Effectiveness Through 12 Years After Vaccine Introduction in the United States, 2003 to 2018. Ann Intern Med. 2022;175(7):918-926.  [PMID:35576590]

    Comment: NHANES data demonstrates how the introduction of HPV vaccination has lowered 4vHPV-type prevalence by 85% overall in 2015-2018, including 90% among vaccinated females and 74% among unvaccinated females, highlighting a herd immunity benefit

  2. Palefsky JM, Lee JY, Jay N, et al. Treatment of Anal High-Grade Squamous Intraepithelial Lesions to Prevent Anal Cancer. N Engl J Med. 2022;386(24):2273-2282.  [PMID:35704479]

    Comment: Landmark study was the first to show that, like cervical cancer, anal cancer can be prevented through precancerous lesions (HSIL) treatment.
    Rating: Important

  3. Thompson MA, Horberg MA, Agwu AL, et al. Primary Care Guidance for Persons With Human Immunodeficiency Virus: 2020 Update by the HIV Medicine Association of the Infectious Diseases Society of America. Clin Infect Dis. 2021;73(11):e3572-e3605.  [PMID:33225349]

    Comment: This updated guide to the primary care of HIV-infected persons now endorses screening HIV-infected persons with anal cytology to permit early detection of and precursors to anal cancer, provided access to appropriate referral and follow-up is available.

  4. Rosenblum HG, Lewis RM, Gargano JW, et al. Declines in Prevalence of Human Papillomavirus Vaccine-Type Infection Among Females after Introduction of Vaccine - United States, 2003-2018. MMWR Morb Mortal Wkly Rep. 2021;70(12):415-420.  [PMID:33764964]

    Comment: NHANES data demonstrate the way in which the introduction of HPV vaccination has lowered HPV prevalence by 81% (females aged 20-24y) and 88% (females aged 14-19y) compared with the pre-vaccine era

  5. Egemen D, Cheung LC, Chen X, et al. Risk Estimates Supporting the 2019 ASCCP Risk-Based Management Consensus Guidelines. J Low Genit Tract Dis. 2020;24(2):132-143.  [PMID:32243308]

    Comment: Explanation of the risk estimates supporting consensus guidelines established in 2019 by the American Society for Colposcopy and Cervical Pathology regarding the management of abnormal findings from cervical cancer screening. Source data include 1.5 million individuals screened through Kaiser Permanente from 2003-2017.

  6. Stefanaki C, Lagogiani I, Kouris A, et al. Cryotherapy versus imiquimod 5% cream combined with a keratolytic lotion in cutaneous warts in children: A randomized study. J Dermatolog Treat. 2016;27(1):80-2.  [PMID:25886088]

    Comment: A small study in children demonstrated that imiquimod 5% + salicylic acid 15% was superior to cryotherapy in eradicating plantar warts at three months. There were no differences in eradication rates for common and plane warts between the two groups.

  7. Panagiotou OA, Befano BL, Gonzalez P, et al. Effect of bivalent human papillomavirus vaccination on pregnancy outcomes: long term observational follow-up in the Costa Rica HPV Vaccine Trial. BMJ. 2015;351:h4358.  [PMID:26346155]

    Comment: Observational long-term follow-up data obtained from women who received bivalent HPV vaccination showed no risk of miscarriage for pregnancies conceived less than 90 days from vaccination. Among pregnancies conceived at any time from bivalent HPV vaccination, exposure was not associated with an increased risk of miscarriage overall or in subgroups, except for miscarriages at weeks 13-20 (relative risk 1.35), suggesting a need for further study.

  8. Olguin-García MG, Jurado-Santa Cruz F, Peralta-Pedrero ML, et al. A double-blind, randomized, placebo-controlled trial of oral isotretinoin in the treatment of recalcitrant facial flat warts. J Dermatolog Treat. 2015;26(1):78-82.  [PMID:24547881]

    Comment: Placebo-controlled study of 31 adults with treatment-refractory facial flat warts showed a significant benefit of treatment with isotretinoin 30 mg/d for twelve weeks.

  9. Joura EA, Giuliano AR, Iversen OE, et al. A 9-valent HPV vaccine against infection and intraepithelial neoplasia in women. N Engl J Med. 2015;372(8):711-23.  [PMID:25693011]

    Comment: This randomized, double-blind study in 14,215 women showed the 9vHPV vaccine prevented cervical, vulvar, and vaginal disease and persistent infection associated with HPV-31, 33, 45, 52, and 58. Antibody responses to HPV-6, 11, 16, 18 were noninferior to those among participants who received the 4vHPV vaccine, and the incidence of disease related to HPV-6, 11, 16, and 18 was similar in the two vaccine groups.

  10. Sterling JC, Gibbs S, Haque Hussain SS, et al. British Association of Dermatologists' guidelines for the management of cutaneous warts 2014. Br J Dermatol. 2014;171(4):696-712.  [PMID:25273231]

    Comment: Nice guideline document that lists the many therapeutics that have been utilized to manage cutaneous warts. Only salicylic acid gets an "A" recommendation, based in part upon studies referenced in the 2012 Cochrane review listed above.

  11. Massad LS, Einstein MH, Huh WK, et al. 2012 updated consensus guidelines for the management of abnormal cervical cancer screening tests and cancer precursors. Obstet Gynecol. 2013;121(4):829-846.  [PMID:23635684]

    Comment: ACOG guideline statement includes recommendations for cervical cancer screening and the management of abnormal findings. In average-risk women, beginning screening at age 21 is recommended. For women 30-65, screening with either (a) cytology every three years or (b) cytology + HPV DNA testing every five years is recommended.

  12. Kwok CS, Gibbs S, Bennett C, et al. Topical treatments for cutaneous warts. Cochrane Database Syst Rev. 2012.  [PMID:22972052]

    Comment: This lengthy review of topical therapies for cutaneous warts finds that only salicylic acid is superior to placebo, despite the many previously pursued remedies.

  13. Sturgis EM, Cinciripini PM. Trends in head and neck cancer incidence in relation to smoking prevalence: an emerging epidemic of human papillomavirus-associated cancers? Cancer. 2007;110(7):1429-35.  [PMID:17724670]

    Comment: This paper synthesizes and reviews head and neck cancer incidence and smoking prevalence over the past 70 years. Notably, squamous cell carcinoma of the head and neck (SCCHN) has declined due to decreased smoking rates. However, certain HN cancers have not shown a similar decline, particularly among young adults < 45 years of age. These include cancer of the tongue and pharynx (including tonsils with a 4% increase per year over the past 30 years). This trend is thought to reflect the increase in HPV 16/18 associated cancers with the likely exposures via oral sex. Current recommendations for immunizing only females with the current HPV vaccine are noted, and note the need to study vaccine safety and efficacy in males.
    Rating: ImportantImportantImportant

  14. Castle PE, Schiffman M, Glass AG, et al. Human papillomavirus prevalence in women who have and have not undergone hysterectomies. J Infect Dis. 2006;194(12):1702-5.  [PMID:17109342]

    Comment: A prevalence study report from the National Cancer Institute NIH examines the prevalence of HPV among age-matched women enrolled in a large northwest U.S. HMO stratified by hysterectomy history (n=573 with hysterectomy [WH] and n=581 with no hysterectomy [WNH[). Routine pelvic examinations were conducted, ethanol-fixed Pap smears were collected (cuff smears collected on WH), and a vaginal lavage using 10 mL of normal saline was conducted. The washed sample was used for HPV testing. There was no significant difference in HPV infection status between the 2 groups [WH=86.2% HPV negative vs. WNH=84.0%] nor a difference in HPV genotype distribution among the 2 groups [WH=1.4% with HPV-16 vs. WNH=1.6% and WH=9.2% non-oncogenic types vs. WNH=9.5%] Notably, however, in the absence of a cervix, WH women are at lower risk of cancer in the presence of HPV-16 than those women with a cervix in place (WNH).
    Rating: Important

  15. Villa LL, Costa RL, Petta CA, et al. High sustained efficacy of a prophylactic quadrivalent human papillomavirus types 6/11/16/18 L1 virus-like particle vaccine through 5 years of follow-up. Br J Cancer. 2006;95(11):1459-66.  [PMID:17117182]

    Comment: This Merck Research Laboratories-funded study reports on data collected during its multicenter phase II/III RCTs (used to support their now licensed vaccine), examining the efficacy of prophylactic quadrivalent HPV 6/11/16/18 L1 VLP vaccine during up to 5 years of follow-up. 552 women (age 16-23 years) were enrolled in the trial from Brazil, Finland, Sweden, Norway, and the USA; 276 entered the vaccination arm of the trial and 275 into the placebo arm. After vaccination on days 0, 2m, and 6 m, 256 women entered follow-up for months 7-36 and 260 similarly were followed in the placebo arm. After 3 years, the non-USA participants were eligible for further follow-up for 2 years. At the 5-year point, the overall incidence of infection with vaccine-containing genotypes was reduced 96% in the vaccine vs the placebo group. There was no vaccine genotype-related precancerous lesions or genital warts in the vaccinated group compared with 6 in the placebo arm (95% CI = 12-100%). The anti-HPV geometric mean titers in sera remained significantly higher among vaccinees than among women who became infected with one or more of the 4 vaccine genotypes during the follow-up period.
    Rating: Important

  16. Arain S, Walts AE, Thomas P, et al. The Anal Pap Smear: Cytomorphology of squamous intraepithelial lesions. Cytojournal. 2005;2(1):4.  [PMID:15715910]

    Comment: Report of a study to determine the usefulness and limitations of anal pap smears in screening for anal squamous intraepithelial lesions (ASIL) among 198 of 200 consecutively liquid media-based collected smears. The findings from these slides were correlated with surgical biopsies. Subsequently, the authors examined the findings at 6 months -- follow-up testing (smears and biopsies)-- among men (n = 71) who returned for evaluation by their usual providers. Liquid-based anal smears had a high sensitivity (98%) for detecting ASIL but a low specificity (50%) for predicting the severity of the abnormality in the subsequent biopsy. Patients with cytologic diagnoses of atypical squamous cells of undetermined significance (ASC-US) and low-grade SIL (LSIL) had a significant risk (46-56%) of HSIL at biopsy. These data suggest that 1) liquid collection media is more sensitive than slide Pap smear results reported in the literature and 2) all patients with a diagnosis of ASC-US and above be recommended for biopsy.
    Rating: Important

  17. Rubin MA, Kleter B, Zhou M, et al. Detection and typing of human papillomavirus DNA in penile carcinoma: evidence for multiple independent pathways of penile carcinogenesis. Am J Pathol. 2001;159(4):1211-8.  [PMID:11583947]

    Comment: A study of penile condylomata, dysplasia and carcinoma histological subtypes using PCR was applied to formalin-fixed, paraffin-embedded tissue samples from US and Paraguay. HPV DNA in 42% of penile CA; 90% of dysplasia; 100% condyloma. Keratinizing SCC and verrucous CA were much less likely to be positive for HPV than basaloid and warty tumor subtypes of CA, suggesting that there may be different pathogenetic mechanisms for penile cancer.
    Rating: Important

  18. Minkoff H, Ahdieh L, Massad LS, et al. The effect of highly active antiretroviral therapy on cervical cytologic changes associated with oncogenic HPV among HIV-infected women. AIDS. 2001;15(16):2157-64.  [PMID:11684935]

    Comment: The Women’s Interagency HIV study was conducted in 5 US cities among HIV-infected women using a q6 mo Pap smear and cervicovaginal lavage for HPV DNA testing stratified by HAART exposure. Women w/ persistent HPV are more likely to have lesions progress. CD4 cell count and Pap smear status adjusted data found women on HAART 40% more likely to have regression of lesions.
    Rating: Important

  19. Woodman CB, Collins S, Winter H, et al. Natural history of cervical human papillomavirus infection in young women: a longitudinal cohort study. Lancet. 2001;357(9271):1831-6.  [PMID:11410191]

    Comment: A very important contribution to our understanding of the natural hx of genital HPV in women. A 3-yr cohort study of 1075 15-19 y/o women who were cytologically WNL and HPV neg at the start. Cumulative incidence of HPV infection over 3 years was 44% w/HPV type 16, the most common type. Among 246 w/ abnormal Pap, 28 progressed to high-grade. High viral load appeared to be associated with a higher cumulative risk of having an abnormal Pap smear.

  20. Kjaer SK, Chackerian B, van den Brule AJ, et al. High-risk human papillomavirus is sexually transmitted: evidence from a follow-up study of virgins starting sexual activity (intercourse). Cancer Epidemiol Biomarkers Prev. 2001;10(2):101-6.  [PMID:11219765]

    Comment: This was an outstanding clinical study conducted by these Danish investigators to determine the role of sexual intercourse in HPV transmission, examine the determinants for seroconversion, and the correlation between HPV DNA, abnormal cervical cytology, and serological response to HPV 16. 100 virgins and 105 monogamous women were randomly selected from a population-based cohort in Denmark. Only virgins who initiated sexual activity became HPV DNA positive. The most important determinant for the acquisition was the number of sexual partners between the 2 examinations conducted during the 2-yr study.

  21. Rousseau MC, Pereira JS, Prado JC, et al. Cervical coinfection with human papillomavirus (HPV) types as a predictor of acquisition and persistence of HPV infection. J Infect Dis. 2001;184(12):1508-17.  [PMID:11740725]

    Comment: A cohort of 1400 Brazilian women was examined for an association between an index HPV infection and its effect on the acquisition and persistence of other types. This question is important to vaccine development if only certain virus types are targeted. The persistence of HPV infection appeared to be independent of the presence of coinfection with multiple types, including type 16, which is associated with approximately 50% of cervical cancers.

  22. Schlecht NF, Kulaga S, Robitaille J, et al. Persistent human papillomavirus infection as a predictor of cervical intraepithelial neoplasia. JAMA. 2001;286(24):3106-14.  [PMID:11754676]

    Comment: A landmark cohort study examining the natural history of HPV in 1611 Brazilian women with no cytological lesions on enrollment and HPV test results from the 1st 2 study visits. Repeated measurements were taken over 24 months. Incidence of SILs was 0.73/1000 women-months among those free of HPV at the initial 2 visits; 8.68 among women w/ HPV type 16 or 18 persisting over both visits. RR of incident SIL was 10.19 for persistence with any oncogenic type; higher among those with HPV 16 and 18. It supports the use of an algorithm that incorporates HPV testing if ASCUS is identified.
    Rating: Important

  23. Ho GY, Bierman R, Beardsley L, et al. Natural history of cervicovaginal papillomavirus infection in young women. N Engl J Med. 1998;338(7):423-8.  [PMID:9459645]

    Comment: 608 women were followed at 6-mo intervals over 3 yrs. the cumulative 36-month incidence of HPV infection was 43% (C.I. 36-49%). Avg annual incidence was 14%. The median duration of new infections was 7 to 10 mo. Persistence of HPV for >6 mo related to older age, type of HPV associated w/cervical CA, and infection with multiple types of HPV. Risk factors for infection: younger age, Hispanic ethnicity, black race, increased number of vaginal sex partners, high freq of vaginal sex, alcohol consumption, anal sex, partner with a high number of lifetime sex partners, and who was not in school.
    Rating: Important

  24. Palefsky JM, Holly EA, Ralston ML, et al. Prevalence and risk factors for human papillomavirus infection of the anal canal in human immunodeficiency virus (HIV)-positive and HIV-negative homosexual men. J Infect Dis. 1998;177(2):361-7.  [PMID:9466522]

    Comment: This is a report of a study to characterize anal HPV among MSM (n=346) and without (n=262) HIV infection recruited from enrollees among 3 San Francisco cohorts groups. Polymerase chain reaction (PCR) detected HPV DNA in anal specimens collected using dacron swabs placed in transport media in 93% of HIV-positive (H-Pos) and 61% of HIV-negative (H-Neg) men. The detected HPV genotype spectrum was similar in both groups, with HPV-16, an oncogenic genotype, the most commonly detected. Coinfection with multiple HPV types: H-Pos=73%, H-Neg=23%. A first-generation hybrid capture assay on unamplified collected material was used to examine oncogenic genotype (16/18/31/33/35/39/45/51/52/56/58) and non-oncogenic (6/11/42/43/44) spectra of infection among H-Pos men. Lower CD4 count was associated with higher oncogenic levels compared to non-oncogenic types. HIV-positive men who were positive by hybrid capture for group B HPV type (p< 0.005.
    Rating: Important

  25. Marrazzo JM, Koutsky LA, Stine KL, et al. Genital human papillomavirus infection in women who have sex with women. J Infect Dis. 1998;178(6):1604-9.  [PMID:9815211]

    Comment: Genital HPV, determined by polymerase chain reaction (PCR) detection of HPV DNA (genotypes 6, 11, 16, 18, 31, 33, 35, 39, and 45) and prevalence of HPV-6 and -16 serum antibodies, was investigated in 149 women who were sexually active with women. HPV DNA was detected in 30% of subjects; of these, 20% had type 31/33/35/39, 18% had type 16, and 2% had type 6/11. 21 subjects reported no prior sex with men; HPV DNA was detected in 19% and squamous intraepithelial lesions in 14%. Current smoking status correlated with detectable HPV DNA.
    Rating: Important

  26. MASSING AM, EPSTEIN WL. Natural history of warts. A two-year study. Arch Dermatol. 1963;87:306-10.  [PMID:13933441]

    Comment: An old study assessed the natural history of warts by following 1000 institutionalized children for two years. Source of the oft-repeated statement that two-thirds of warts spontaneously resolve in two years.


Common wart

Descriptive text is not available for this image

Wart on finger, termed verruca vulgaris or the common wart.

Source CDC/R.S. Hibbets

Plantar wart

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Upon paring down lesion, evidence of thrombosed capillaries distinguish from callus. Also, calluses tend to be non-painful.

Source: Wikimedia, Δρ. Χαράλαμπος Γκούβας

Flat wart

Descriptive text is not available for this image

Flat wart, also called verruca plana, in a middle-aged women.

Source: Wikimedia commons

Iffat Hassan, Taseer Bhat, Hinah Altaf, Farah Sameem, Qazi Masood

Last updated: September 3, 2022