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HPV-Related Diseases in HIV-Infected Individuals (18HH01)

Debra Chew, MD, MPH, Clinical Assistant Professor, Division of Infectious Diseases, Department of Medicine, Rutgers New Jersey Medical School, Lisa Dever, MD, Vice Chair for Faculty Development in the Department of Medicine, Clinical Chief of Infectious Diseases and the Director of the Infectious Disease Fellows, Rutgers New Jersey Medical School, and Shobha Swaminathan, MD, Assistant Professor, Division of Infectious Diseases, Department of Medicine, Rutgers New Jersey Medical School

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Anogenital Warts in HIV-Infected Individuals

Anogenital warts (condyloma accuminata) are more common, severe, and recalcitrant to treatment in HIV-infected individuals compared to non-infected persons.83-86 Diagnosis of genital warts can usually be made by visual inspection of the affected area, and typically appear as flat, papular, or pedunculated lesions that are skin-colored or pink. Most warts are asymptomatic, but may cause pruritis and discomfort. Advanced immunosuppression is associated with more extensive disease, and depending on size and location of lesions, may cause dyspareunia or dyschezia. The extent of involvement should be determined by further evaluation with high resolution anoscopy, colposcopy and/or vaginal speculum examination as appropriate, and typically appear acetowhite with application of 5% acetic acid. Since high-grade squamous intraepithelial lesions and carcinomas are more common in HIV-infected persons and may arise in or resemble genital warts, biopsy is indicated to confirm diagnosis in suspected lesions. Biopsy should be done also if diagnosis is uncertain, if lesions do not respond to standard therapy, or if lesions are atypical, pigmented, indurated, fixed, bleeding, or ulcerated.49

Similar to the uninfected population, small condylomas may be treated with local topical treatment (patient applied podophyllotoxin cycles of 3 days on and 4 days off) or imiquimod or provider-applied liquid nitrogen or trichloroacetic acid), local ablation or surgical excision while more extensive lesions can be approached medically with the application of imiquimod or 5-fluorouracil or surgical intervention.49 Some studies have found a regression of anogenital warts with cART,87 whereas other studies have reported increased rates of oral warts following cART initiation.88-89

Human papilloma virus, HPV

© Estiot Veronique/Oredia

Other HPV-Associated Cancers in HIV-Infected Individuals

As with other HPV-associated cancers, persons with HIV/AIDS have higher incidence of vulva, vaginal, penile, and oropharyngeal cancers compared to the general population. AIDS cancer registry match studies have found that the risk for oropharyngeal cancer is 1.5-4 fold higher among HIV-infected individuals compared with non-infected persons. 6-7 Chaturvedi et al. found a 5.3%, 5.8% and 1.6% increase risk for cancer of the penis, vaginal or vulva and oropharyngeal cancer respectively among persons with AIDS.7 Unlike cervical and anal cancers, only a subset of these cancers is associated with HPV. HPV-associated oropharyngeal cancers are primarily found in the oropharynx and base of the tongue and tonsil, and are primarily associated with sexual risk factors as opposed to alcohol and tobacco use, traditionally associated with non-HPV associated oropharyngeal cancers. There are currently no clinically available screening tests for detection of oropharyngeal HPV infection.90 Penile, vulvar or vaginal neoplasia are recognized through visual inspection, including high resolution anoscopy, colposcopy, and biopsy as needed.

Treatment of low-grade vulvar and vaginal dysplasia can be observed or managed as for anogenital warts. Treatment modalities for vulvar intraneoplasia include local excision, laser vaporization, ablation and imiquimod therapy. Treatment options for vaginal intraneoplasia include topical 5-FU, laser vaporization with CO2 laser, and excision. For cancers of the penis and oropharynx, treatment is similar in HIV-infected and HIV-uninfected men and women. Current data suggest a more favorable prognosis for HPV-associated oropharyngeal cancers compared with non-HPV associated oropharyngeal cancers.49

HPV Vaccination in HIV-Infected Individuals

Bi-valent (Ceravix®), quadrivalent (Gardasil®), and 9-valent (Gardasil 9®) HPV vaccines are licensed for use in the US and available for the prevention of genital HPV infection in men and women.91-93 Bi-valent HPV vaccine is effective against HPV types 16 and 18. Quadrivalent vaccine targets HPV types 6, 11, 16, and 18, and 9-valent vaccine targets types 6, 11, 16, 18 as well as 31, 33, 45, 52, and 58. The vaccines are composed of type-specific HPV L1 protein, the major capsid protein of HPV. In large clinical trials, bivalent, quadrivalent and 9-valent HPV vaccines have been shown to be nearly 100% efficacious in preventing cervical, vulvar and vaginal intraepithelial neoplasia, and genital warts in healthy women without prior HPV infection94-98 and 78% and 86% effective, respectively, in reducing anal intraepithelial neoplasia and persistent HPV vaccine types among healthy young men.99

However, efficacy of HPV vaccination in the HIV-infected population has not been demonstrated and is currently being evaluated in major clinical trials. Although studies have found bivalent and quadrivalent HPV vaccines to be well tolerated and immunogenic in HIV-infected persons,100-103 it is possible that immunosuppression may attenuate development of protective titers of HPV antibodies. Some studies have found lower geometric mean titers against HPV virus vaccine types among those infected with HIV compared to those uninfected.100,102 Additionally since HPV vaccines are most effective when given to recipients without prior HPV infection, vaccine efficacy might be reduced among HIV-infected individuals who are less likely to be HPV-naïve to vaccine types. Ideally HPV vaccine should be given prior to HPV acquisition and sexual debut.

Human papilloma virus (HPV).

Image produced using high-dynamic-range imaging (HDRI) from an image taken with transmission electron microscopy. Viral diameter around 55 nm.

Credit: Cavallini James/BSI /BSIP

At the current time, CDC recommends routine HPV vaccination for HIV-infected individuals age 11 through 26 years who have not been previously vaccinated.104 The quadrivalent vaccine and 9-valent vaccines are administered in 3 doses at time zero, and at 2 and 6 months following initial dose. The bivalent vaccine is administered in 3 doses at time zero and at 1 and 6 months following initial dose.104

Patients should also be counseled on use of male or female condoms (made of latex or polyurethane) to prevent transmission or acquisition of HPV infection and other sexually transmitted diseases. Studies have shown consistent condom use has been associated with a 70% lower incidence of oncogenic HPV infection among women105 and a reduced risk of genital warts and CIN in women.106

Conclusions

The burden of HPV-related disease is high among HIV-infected individuals and carries increased risk for cervical and other anogenital tract and oral-pharyngeal cancers compared to HIV-uninfected persons. While routine cervical cytologic screening has significantly reduced the incidence of cervical cancer in the US, rates of anal cancer continue to rise in the US in the general and HIV-infected population. Significant gaps still remain in the management of anal dysplasia and in primary HPV prevention in persons with HIV infection. Treatment data on anal dysplasia are limited and more effective treatments are needed. Further studies to determine the effectiveness of routine anal cancer screening, and whether screening will be beneficial in earlier cancer detection and reduce the incidence of anal cancer are also needed. Until such consensus guidelines are established, we should develop the necessary infrastructure to make HRA readily available to perform routine anal cytologic screening in HIV-infected individuals and offer treatment for anal dysplasia. HIV-infected patients should be counseled and educated about HPV and their increased risk for HPV-associated cancers. Providers should adhere to cervical cancer screening and treatment guidelines. While vaccine efficacy among HIV-infected individuals is still being evaluated, HPV vaccine should be given to eligible patients and may potentially prevent vaccine-type HPV-associated anogenital precancers, cancers, and condylomas. It is hoped that universal HPV vaccination among adolescent males and females will reduce the overall burden of HPV disease.


 
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