Prevention and Management of Human Papillomavirus Infection in Adults With HIV

Prevention and Management of Human Papillomavirus Infection in Adults With HIV

Purpose of This Guideline

Reviewed and updated: Meera Shah, MD, MPH, MS, AAHIVS; November 4, 2022
Writing group: Steven M. Fine, MD, PhD; Rona M. Vail, MD; Samuel T. Merrick, MD; Asa E. Radix, MD, MPH, PhD; Charles J. Gonzalez, MD; Christopher J. Hoffmann, MD, MPH
Committee: Medical Care Criteria Committee
Date of original publication: May 2013

This guideline on human papillomavirus (HPV) in individuals with HIV was developed by the New York State Department of Health AIDS Institute (NYSDOH AI) to inform primary care providers and other practitioners in New York State about HPV prevention, screening methods, diagnosis and presentation, and treatment in adults with HIV. This guideline aims to achieve the following goals:

  • Increase the number of New York State residents with HIV who are screened and effectively treated for HPV-related dysplasia. 
  • Support the NYSDOH Prevention Agenda 2019-2024 by educating care providers on the importance of HPV vaccination and increasing the rate of 3-dose HPV immunization among individuals with HIV.
  • Reduce the morbidity and mortality associated with HPV in people with HIV through early identification and treatment of potentially precancerous and cancerous lesions, when treatment is most likely to be effective.

HPV-Associated Cancers

Reviewed and updated: Meera Shah, MD, MPH, MS, AAHIVS, with the Medical Care Criteria Committee; November 4, 2022

HPV-associated cancers: Cervical cancer rates have decreased because of a robust screening system in the United States that has been in place since the 1960s [NCI 2022a]. The incidence of anal cancer persists, particularly among men who have sex with men (MSM) with or without HIV and among women with HIV [Islami, et al. 2017; Palefsky 2017; Hessol, et al. 2013], and approximately 91% of anal cancers are thought to be caused by human papillomavirus (HPV) [CDC 2022a].

This Committee has recommended anal screening for specific subpopulations of individuals with HIV since 2007 and recently expanded the recommendation to include anal cytology screening for MSM, cisgender women, transgender women, and transgender men who have HIV and are ≥35 years old (see the NYSDOH AI guideline Screening for Anal Dysplasia and Cancer in Adults With HIV). Anal Cancer HSIL Outcomes Research (ANCHOR) study investigators announced by press release in October 2021 that treatment of precancerous lesions reduced anal cancer risk among people with HIV [ANCHOR 2021]. Although screening tests are available for oropharyngeal cancers, the utility and benefits have not been established; therefore, screening other than visual inspection is not yet recommended (see American Dental Association > Evaluation of Potentially Malignant Disorders in the Oral Cavity Clinical Practice Guideline [2017] for more information). There are no routine screening tests or procedures for vulvar, vaginal, or penile cancers.

HPV types: There are many HPV types, some of which cause cancer (oncogenic) and others of which cause noncancerous disease (nononcogenic verruca vulgaris and condyloma acuminata). Approximately 30 different HPV types infect cells in the anus and genital tract, including the cervix, and may cause asymptomatic infection, condylomata acuminata (genital warts), squamous intraepithelial lesions (SILs), glandular cell abnormalities, and anal and cervical cancer or other genital carcinomas. HPV is also associated with oropharyngeal cancer [CDC 2022a, 2022b]. HPV infection is often asymptomatic, and the time course from initial infection to the presence of lesions has not been determined, preventing a reliable method for determining the source and time of acquisition.

In the general U.S. population, HPV types 16 and 18 are responsible for approximately 70% of cases of cervical and anal SILs and cervical and anal cancers [Lowy and Schiller 2012; Steinbrook 2006] in addition to most oropharyngeal, vaginal, vulvar, and penile cancers [Saraiya, et al. 2015; Forman, et al. 2012; Grulich, et al. 2010; Bouvard, et al. 2009]. Nononcogenic HPV types 6 and 11 cause >90% of genital warts [CDC 2021; Workowski, et al. 2021]. A wider range and higher prevalence of HPV types responsible for oncogenic and nononcogenic disease have been documented in people with HIV [Massad, et al. 2016; Kojic, et al. 2011; Clifford, et al. 2006]. HPV-associated cancers occur more often among people with HIV than in the general population [Liu, et al. 2018; Jemal, et al. 2013], and the distribution of HPV types responsible for SILs and warts also differs between these populations [Clifford, et al. 2006].

High-risk HPV types that are related to anogenital cancers include types 16, 18, 26, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66, 67, 68, 69, 70, 73, and 82 [Guan, et al. 2012; Hariri, et al. 2012]. Although high-risk HPV types are detected in 99% of cervical cancers, types 16 and 18 are the most oncogenic [Clifford, et al. 2017; Keller, et al. 2015] and account for nearly 70% of all cervical cancers in the general population [CDC 2021]. HPV type 16 is the most common high-risk type among individuals with or without HIV [Lin, et al. 2018]. Among individuals with HIV, cervical cancer is associated with types 16 and 18 and high-risk types 51, 52, 53, 56, 58, and 59 [McKenzie, et al. 2010]. High-risk HPV types other than type 16 are more common and are more frequently associated with anal cancer among MSM with HIV than MSM without HIV [Poynten, et al. 2021]. Infection with more than one HPV type occurs more frequently among individuals with HIV, and these individuals can be at risk of cervical and anal SILs and nonmalignant disease simultaneously [Castilho, et al. 2015; Clifford, et al. 2006].

Tobacco use: Tobacco use is an established contributor to the oncogenic potential of HPV and is an independent risk factor for acquisition and progression of cervical SILs [Collins, et al. 2010], anal neoplasia [Daling, et al. 2004], oropharyngeal cancer [NCI 2022b], and vulvar cancer in individuals with HIV [ACS 2018; Kutlubay, et al. 2013]. Some data suggest that HIV-related immune suppression can contribute to relapse and progression of HPV disease, and antiretroviral therapy-mediated immune reconstitution can lead to regression of SILs associated with HPV infection [Blitz, et al. 2013]. Other studies do not support this finding [Piketty, et al. 2013; Adler 2010].

References

ACS. Risk factors for vulvar cancer. 2018 Jan 16. https://www.cancer.org/cancer/vulvar-cancer/causes-risks-prevention/risk-factors.html [accessed 2022 Oct 17]

Adler DH. The impact of HAART on HPV-related cervical disease. Curr HIV Res 2010;8(7):493-497. [PMID: 20946095

ANCHOR. Press release: treating anal cancer precursor lesions reduces cancer risk for people with HIV. 2021 Oct 7. https://iansoc.org/resources/ANCHOR%20press%20release_07OCT2021.pdf [accessed 2022 Oct 17]

Blitz S, Baxter J, Raboud J, et al. Evaluation of HIV and highly active antiretroviral therapy on the natural history of human papillomavirus infection and cervical cytopathologic findings in HIV-positive and high-risk HIV-negative women. J Infect Dis 2013;208(3):454-462. [PMID: 23624362

Bouvard V, Baan R, Straif K, et al. A review of human carcinogens–Part B: biological agents. Lancet Oncol 2009;10(4):321-322. [PMID: 19350698

Castilho JL, Levi JE, Luz PM, et al. A cross-sectional study of high-risk human papillomavirus clustering and cervical outcomes in HIV-infected women in Rio de Janeiro, Brazil. BMC Cancer 2015;15:478. [PMID: 26100400

CDC. Epidemiology and prevention of vaccine-preventable diseases: Human papillomavirus. 2021 Aug 18. https://www.cdc.gov/vaccines/pubs/pinkbook/hpv.html [accessed 2022 Oct 17]

CDC. How many cancers are linked with HPV each year? 2022a Oct 3. https://www.cdc.gov/cancer/hpv/statistics/cases.htm [accessed 2022 Oct 17]

CDC. HPV-associated cancer diagnosis by age. 2022b Oct 3. https://www.cdc.gov/cancer/hpv/statistics/age.htm [accessed 2022 Oct 17]

Clifford GM, Goncalves MA, Franceschi S. Human papillomavirus types among women infected with HIV: a meta-analysis. AIDS 2006;20(18):2337-2344. [PMID: 17117020

Clifford GM, Tully S, Franceschi S. Carcinogenicity of human papillomavirus (HPV) types in HIV-positive women: a meta-analysis from HPV infection to cervical cancer. Clin Infect Dis 2017;64(9):1228-1235. [PMID: 28199532

Collins S, Rollason TP, Young LS, et al. Cigarette smoking is an independent risk factor for cervical intraepithelial neoplasia in young women: a longitudinal study. Eur J Cancer 2010;46(2):405-411. [PMID: 19819687

Daling JR, Madeleine MM, Johnson LG, et al. Human papillomavirus, smoking, and sexual practices in the etiology of anal cancer. Cancer 2004;101(2):270-280. [PMID: 15241823

Forman D, de Martel C, Lacey CJ, et al. Global burden of human papillomavirus and related diseases. Vaccine 2012;30 Suppl 5:F12-23. [PMID: 23199955

Grulich AE, Jin F, Conway EL, et al. Cancers attributable to human papillomavirus infection. Sex Health 2010;7(3):244-252. [PMID: 20719211] 

Guan P, Howell-Jones R, Li N, et al. Human papillomavirus types in 115,789 HPV-positive women: a meta-analysis from cervical infection to cancer. Int J Cancer 2012;131(10):2349-2359. [PMID: 22323075

Hariri S, Unger ER, Powell SE, et al. Human papillomavirus genotypes in high-grade cervical lesions in the United States. J Infect Dis 2012;206(12):1878-1886. [PMID: 23045628

Hessol NA, Holly EA, Efird JT, et al. Concomitant anal and cervical human papillomavirusV infections and intraepithelial neoplasia in HIV-infected and uninfected women. AIDS 2013;27(11):1743-1751. [PMID: 23803793

Islami F, Ferlay J, Lortet-Tieulent J, et al. International trends in anal cancer incidence rates. Int J Epidemiol 2017;46(3):924-938. [PMID: 27789668]

Jemal A, Simard EP, Dorell C, et al. Annual Report to the Nation on the Status of Cancer, 1975-2009, featuring the burden and trends in human papillomavirus(HPV)-associated cancers and HPV vaccination coverage levels. J Natl Cancer Inst 2013;105(3):175-201. [PMID: 23297039

Keller MJ, Burk RD, Massad LS, et al. Cervical precancer risk in HIV-infected women who test positive for oncogenic human papillomavirus despite a normal pap test. Clin Infect Dis 2015;61(10):1573-1581. [PMID: 26187020

Kojic EM, Cu-Uvin S, Conley L, et al. Human papillomavirus infection and cytologic abnormalities of the anus and cervix among HIV-infected women in the study to understand the natural history of HIV/AIDS in the era of effective therapy (the SUN Study). Sex Transm Dis 2011;38(4):253-259. [PMID: 20966828

Kutlubay Z, Engin B, Zara T, et al. Anogenital malignancies and premalignancies: facts and controversies. Clin Dermatol 2013;31(4):362-373. [PMID: 23806153

Lin C, Franceschi S, Clifford GM. Human papillomavirus types from infection to cancer in the anus, according to sex and HIV status: a systematic review and meta-analysis. Lancet Infect Dis 2018;18(2):198-206. [PMID: 29158102

Liu G, Sharma M, Tan N, et al. HIV-positive women have higher risk of human papilloma virus infection, precancerous lesions, and cervical cancer. AIDS 2018;32(6):795-808. [PMID: 29369827]

Lowy DR, Schiller JT. Reducing HPV-associated cancer globally. Cancer Prev Res (Phila) 2012;5(1):18-23. [PMID: 22219162

Massad LS, Xie X, Burk RD, et al. Association of cervical precancer with human papillomavirus types other than 16 among HIV co-infected women. Am J Obstet Gynecol 2016;214(3):354.e351-356. [PMID: 26433170]

McKenzie ND, Kobetz EN, Hnatyszyn J, et al. Women with HIV are more commonly infected with non-16 and -18 high-risk HPV types. Gynecol Oncol 2010;116(3):572-577. [PMID: 19906410]

NCI. Cancer stat facts: cervical cancer. 2022a Oct 27. https://seer.cancer.gov/statfacts/html/cervix.html [accessed 2022 Oct 17]

NCI. Oral cavity, oropharyngeal, hypopharyngeal, and laryngeal cancers prevention (PDQ®)–Health professional version. 2022b Jun 23. https://www.cancer.gov/types/head-and-neck/hp/oral-prevention-pdq [accessed 2022 Oct 17]

Palefsky J. Human papillomavirus-associated anal and cervical cancers in HIV-infected individuals: incidence and prevention in the antiretroviral therapy era. Curr Opin HIV AIDS 2017;12(1):26-30. [PMID: 27828801

Piketty C, Cochand-Priollet B, Lanoy E, et al. Lack of regression of anal squamous intraepithelial lesions despite immune restoration under cART. AIDS 2013;27(3):401-406. [PMID: 23079803

Poynten IM, Jin F, Garland SM, et al. HIV, immune dysfunction, and the natural history of anal high-risk human papillomavirus infection in gay and bisexual men. J Infect Dis 2021;224(2):246-257. [PMID: 33220687

Saraiya M, Unger ER, Thompson TD, et al. US assessment of HPV types in cancers: implications for current and 9-valent HPV vaccines. J Natl Cancer Inst 2015;107(6):djv086. [PMID: 25925419

Steinbrook R. The potential of human papillomavirus vaccines. N Engl J Med 2006;354(11):1109-1112. [PMID: 16540608

Workowski KA, Bachmann LH, Chan PA, et al. Sexually transmitted diseases treatment guidelines, 2021. MMWR Recomm Rep 2021;70(RR-4):1-187. [PMID: 26042815

HPV Prevention

Lead authors: Maria Teresa (Tess) Timoney, MS, RN, CNM, and Jessica M. Atrio, MD, MSc, with the Medical Care Criteria Committee; March 25, 2022 > Screening for Cervical Dysplasia and Cancer in Adults With HIV

RECOMMENDATION
HPV Prevention
  • Given the increased lifetime risk of persistent human papillomavirus (HPV) infection and increased prevalence of HPV-related cancers, clinicians should recommend the 9-valent HPV vaccine 3-dose series at 0, 2, and 6 months to all individuals with HIV who are 9 to 45 years old regardless of CD4 cell count, prior cervical or anal screening results, HPV test results, HPV-related cytologic changes, or other history of HPV-related lesions. (A3)

HPV Vaccine

In 2006, the U.S. Food and Drug Administration (FDA) approved a 9-valent vaccine that protects against nononcogenic HPV types 16, 18, 31, 33, 45, 52, and 58 (Gardasil 9). Because it offers broader coverage of HPV types, the 9-valent vaccine is the only HPV vaccine available in the United States (see the Centers for Disease Control and Prevention [CDC] supplemental information and guidance for vaccination providers regarding use of 9-valent HPV for more information). The HPV vaccine is approved by the FDA for preventive but not therapeutic use.

Extrapolating data from the demonstrated effectiveness of the quadrivalent HPV vaccine in older individuals [Wilkin, et al. 2018], the FDA expanded the age range for recommended HPV vaccination in the United States from ages 9 to 26 years to ages 27 to 45 years [FDA 2020]. There is no specific mention of HIV infection in the updated FDA recommendation. Although 1 study demonstrated lower efficacy of the quadrivalent vaccine in individuals with HIV [Wilkin, et al. 2018], other research linked HIV viral suppression to vaccine efficacy [Money, et al. 2016]. Given the increased lifetime burden of persistent HPV infection, disease, and morbidity, proactive vaccination among individuals with HIV is a strategic means of primary prevention and potential disease mitigation that should be strongly considered and encouraged [Di Donato, et al. 2021; Karimi-Zarchi, et al. 2020; Lichter, et al. 2020].

When to Vaccinate

HPV vaccination may be scheduled at the same time as standard adolescent vaccines offered at ages 9 to 12 years. If possible, the vaccine series should begin at age 9 years [Glidden, et al. 2016]. The 3-dose vaccine regimen is recommended for all patients with HIV who are 9 to 45 years old. The 9-valent HPV vaccine should be administered according to the CDC standard schedule for immunocompromised adultschildren, and adolescents (a 3-dose regimen over a 6-month period at 0, 2, and 6 months) and should be offered regardless of CD4 cell count.

HPV vaccination provides high levels of neutralizing antibody for at least 5 years and is protective in individuals ≤26 years old who do not have HIV, regardless of history of sexual activity; however, the full length of its protection has not been established. In an observational study conducted in England that examined the effectiveness of a national HPV immunization program, the reduction in cervical cancer was greatest in individuals who received the vaccine at ages 12 to 13 years [Falcaro, et al. 2021]. Although data are limited, the immunogenicity of the quadrivalent HPV vaccine has been demonstrated in individuals with HIV [Wilkin, et al. 2018; Kojic, et al. 2014].

HPV testing and vaccination: HPV testing is not recommended before vaccine administration. It is unlikely that an individual will have been infected with all the HPV types covered by the 9-valent vaccine; therefore, it is expected that the 9-valent HPV vaccine will be effective against any of the 9 HPV types or any HPV types to which the individual has not been exposed. There also may be beneficial prevention due to cross-reactivity with other HPV types not included in the 9-valent vaccine [Wheeler, et al. 2012].

Revaccination with the 9-valent HPV vaccine is not currently recommended for individuals previously immunized with the bivalent or quadrivalent HPV vaccine [ACOG 2020; Petrosky, et al. 2015]. Vaccination with the quadrivalent HPV vaccine has demonstrated cross-protection against other oncogenic HPV types [Kemp, et al. 2011]. There is no maximum interval between vaccine doses; as long as all 3 doses are given, there is no need to repeat doses if a scheduled vaccination is not given on schedule [CDC 2021a].

KEY POINT
  • HPV testing is not recommended before administration of the HPV vaccine.

Other Forms of HPV Prevention

HPV infection is the most common sexually transmitted infection (STI) in the United States, and many individuals become infected with multiple types of HPV during their lives [CDC 2021b]. Most HPV infections resolve, become latent, or are not detectable on clinical assays within a few years of exposure and infection [Ho, et al. 1998; Moscicki, et al. 1998; Evander, et al. 1995]. HPV is transmitted via skin-to-skin contact, so barrier methods such as condoms offer some but not full protection. Because prior identification of HPV infection in a sexual partner is unlikely, limiting the number of sexual partners may reduce but not eliminate an individual’s exposure to HPV [Workowski, et al. 2021].

KEY POINTS
  • Inform patients with HIV about the risk of acquiring HPV and other STIs from close physical contact with the external genitalia, anus, cervix, vagina, urethra, mouth and oral cavity, or any other location where HPV lesions are present.
  • Consistent and correct condom use remains an effective way to prevent the transmission of most STIs, including HPV. However, inform patients that barrier protection such as condoms and dental dams may not fully protect against HPV.
References

ACOG. Human papillomavirus vaccination: ACOG committee opinion, number 809. Obstet Gynecol 2020;136(2):e15-e21. [PMID: 32732766

CDC. HPV vaccine schedule and dosing. 2021a Nov 1. https://www.cdc.gov/hpv/hcp/schedules-recommendations.html [accessed 2022 Oct 17]

CDC. Sexually transmitted infections prevalence, incidence, and cost estimates in the United States. 2021b Jan 25. https://www.cdc.gov/std/statistics/prevalence-2020-at-a-glance.htm [accessed 2022 Oct 17]

Di Donato V, Caruso G, Petrillo M, et al. Adjuvant HPV vaccination to prevent recurrent cervical dysplasia after surgical treatment: a meta-analysis. Vaccines (Basel) 2021;9(5). [PMID: 33919003

Evander M, Edlund K, Gustafsson A, et al. Human papillomavirus infection is transient in young women: a population-based cohort study. J Infect Dis 1995;171(4):1026-1030. [PMID: 7706782

Falcaro M, Castanon A, Ndlela B, et al. The effects of the national HPV vaccination programme in England, UK, on cervical cancer and grade 3 cervical intraepithelial neoplasia incidence: a register-based observational study. Lancet 2021. [PMID: 34741816

FDA. Gardasil 9. 2020 Aug 21. https://www.fda.gov/vaccines-blood-biologics/vaccines/gardasil-9 [accessed 2022 Oct 17]

Glidden DV, Amico KR, Liu AY, et al. Symptoms, side effects and adherence in the iPrEx open-label extension. Clin Infect Dis 2016;62(9):1172-1177. [PMID: 26797207

Ho GY, Bierman R, Beardsley L, et al. Natural history of cervicovaginal papillomavirus infection in young women. N Engl J Med 1998;338(7):423-428. [PMID: 9459645

Karimi-Zarchi M, Allahqoli L, Nehmati A, et al. Can the prophylactic quadrivalent HPV vaccine be used as a therapeutic agent in women with CIN? A randomized trial. BMC Public Health 2020;20(1):274. [PMID: 32106837

Kemp TJ, Hildesheim A, Safaeian M, et al. HPV16/18 L1 VLP vaccine induces cross-neutralizing antibodies that may mediate cross-protection. Vaccine 2011;29(11):2011-2014. [PMID: 21241731

Kojic EM, Kang M, Cespedes MS, et al. Immunogenicity and safety of the quadrivalent human papillomavirus vaccine in HIV-1-infected women. Clin Infect Dis 2014;59(1):127-135. [PMID: 24723284

Lichter K, Krause D, Xu J, et al. Adjuvant human papillomavirus vaccine to reduce recurrent cervical dysplasia in unvaccinated women: a systematic review and meta-analysis. Obstet Gynecol 2020;135(5):1070-1083. [PMID: 32282601

Money DM, Moses E, Blitz S, et al. HIV viral suppression results in higher antibody responses in HIV-positive women vaccinated with the quadrivalent human papillomavirus vaccine. Vaccine 2016;34(40):4799-4806. [PMID: 27544584

Moscicki AB, Shiboski S, Broering J, et al. The natural history of human papillomavirus infection as measured by repeated DNA testing in adolescent and young women. J Pediatr 1998;132(2):277-284. [PMID: 9506641

Petrosky E, Bocchini JA, Jr., Hariri S, et al. Use of 9-valent human papillomavirus (HPV) vaccine: updated HPV vaccination recommendations of the advisory committee on immunization practices. MMWR Morb Mortal Wkly Rep 2015;64(11):300-304. [PMID: 25811679

Wheeler CM, Castellsagué X, Garland SM, et al. Cross-protective efficacy of HPV-16/18 AS04-adjuvanted vaccine against cervical infection and precancer caused by non-vaccine oncogenic HPV types: 4-year end-of-study analysis of the randomised, double-blind PATRICIA trial. Lancet Oncol 2012;13(1):100-110. [PMID: 22075170

Wilkin TJ, Chen H, Cespedes MS, et al. A randomized, placebo-controlled trial of the quadrivalent human papillomavirus vaccine in human immunodeficiency virus-infected adults aged 27 years or older: AIDS Clinical Trials Group Protocol A5298. Clin Infect Dis 2018;67(9):1339-1346. [PMID: 29659751

Workowski KA, Bachmann LH, Chan PA, et al. Sexually transmitted diseases treatment guidelines, 2021. MMWR Recomm Rep 2021;70(RR-4):1-187. [PMID: 26042815

Cervical and Anal Cancer Screening

Reviewed and updated: Meera Shah, MD, MPH, MS, AAHIVS, with the Medical Care Criteria Committee; November 4, 2022

RECOMMENDATIONS
Cervical and Anal Cancer Screening
  • Clinicians should perform cervical and anal cytologic screening for individuals with HIV, regardless of their human papillomavirus (HPV) vaccination status, as recommended in the NYSDOH AI guidelines Screening for Cervical Dysplasia and Cancer in Adults With HIV and Screening for Anal Dysplasia and Cancer in Adults With HIV. (A3)
  • Clinicians should examine the neovagina in transgender women who have undergone vaginoplasty to assess for visible HPV lesions at baseline and during the annual comprehensive physical examination; examination can be done using an anoscope, a small vaginal speculum, or a nasal speculum. (A3)
  • At each routine monitoring visit, clinicians should ask all patients about sexual behaviors and new sex partners to assess for risk behaviors that require repeat or ongoing screening. (A3)

Cervical cancer screening: Clinicians should perform cervical and anal cytologic screening for people with HIV according to the recommendations in the NYSDOH AI guidelines Screening for Cervical Dysplasia and Cancer in Adults With HIV and Screening for Anal Dysplasia and Cancer in Adults With HIV. HPV testing with cytologic screening enhances the identification of HPV-related cervical disease in individuals with HIV. Examination of the anogenital area of patients with HIV to assess for visible HPV lesions is necessary because HPV can also infect the urethra and the external genitalia [Ehrenpreis and Smith 2018; Leeds and Fang 2016; Tyerman and Aboulafia 2012; Weyers, et al. 2010]. Speculum examination of the vagina, neovagina, and cervix and anoscopic examination of the anus and lower rectum may also reveal lesions. There are currently no data on urethral screening and treatment, but referral to a urologist will facilitate appropriate assessment and management when this is a concern.

Anal cancer screening: Anal squamous intraepithelial lesions (SILs) have been associated with concurrent cervical SILs; however, they also occur independently. Anal cytology should be performed for all cisgender women with HIV [Gaisa, et al. 2017; Stier, et al. 2015; Hessol, et al. 2013; Kojic, et al. 2011], with or without cervical abnormalities, according to guidelines for adults with HIV. See the NYSDOH AI guideline Screening for Anal Dysplasia and Cancer in Adults With HIV. Although there are no specific data on transgender men or transgender women, anal screening is also recommended for these populations.

Transgender individuals: It is important that care providers and facilities establish a safe and welcoming environment for transgender patients [Deutsch 2016]. Approximately one-third of transgender or gender-diverse individuals assigned female sex at birth identify as nonbinary [James, et al. 2016]. Asking patients to provide details about all gender-affirming and gynecologic surgical procedures will help establish the need for screening for HPV-related cancers. See University of California San Francisco Gender-Affirming Health Program for terminology and definitions related to transgender care.

Sexual history: Discussion of sexual health, including a patient’s history of sexually transmitted infections (STIs), is an important component of the baseline and annual assessments and is an opportunity to discuss a patient’s concerns and questions. The frequency of the sexual health assessment is based on risk factors. It is particularly important to use nonjudgmental, sex-positive language in this discussion to establish a strong connection and facilitate open discussion. See the NYSDOH AI resource GOALS Framework for Sexual History Taking in Primary Care.

KEY POINTS
  • Regardless of cytology results, it is important that screening for STIs is performed routinely in patients who engage in risk behaviors.
  • Assessment for visible HPV lesions in individuals with HIV can be accomplished through baseline and then annual examination of the periurethral and anogenital areas and the vagina and cervix.
References

Deutsch MB. UCSF transgender care & treatment guidelines: Creating a safe and welcoming clinic environment. 2016 Jun 17. https://transcare.ucsf.edu/guidelines/clinic-environment [accessed 2022 Oct 17]

Ehrenpreis ED, Smith DG. Patients with newly diagnosed cervical cancer should be screened for anal human papilloma virus and anal dysplasia: Results of a pilot study using a STELLA computer simulation and economic model. Papillomavirus Res 2018;5:38-45. [PMID: 29272853

Gaisa M, Ita-Nagy F, Sigel K, et al. High rates of anal high-grade squamous intraepithelial lesions in HIV-infected women who do not meet screening guidelines. Clin Infect Dis 2017;64(3):289-294. [PMID: 27965301

Hessol NA, Holly EA, Efird JT, et al. Concomitant anal and cervical human papillomavirusV infections and intraepithelial neoplasia in HIV-infected and uninfected women. AIDS 2013;27(11):1743-1751. [PMID: 23803793

James SE, Herman JL, Rankin S, et al. The Report of the 2015 U.S. Transgender Survey. National Center for Transgender Equality. 2016 Dec. https://transequality.org/sites/default/files/docs/usts/USTS-Full-Report-Dec17.pdf [accessed 2022 Oct 17]

Kojic EM, Cu-Uvin S, Conley L, et al. Human papillomavirus infection and cytologic abnormalities of the anus and cervix among HIV-infected women in the study to understand the natural history of HIV/AIDS in the era of effective therapy (the SUN Study). Sex Transm Dis 2011;38(4):253-259. [PMID: 20966828

Leeds IL, Fang SH. Anal cancer and intraepithelial neoplasia screening: A review. World J Gastrointest Surg 2016;8(1):41-51. [PMID: 26843912

Stier EA, Sebring MC, Mendez AE, et al. Prevalence of anal human papillomavirus infection and anal HPV-related disorders in women: a systematic review. Am J Obstet Gynecol 2015;213(3):278-309. [PMID: 25797230

Tyerman Z, Aboulafia DM. Review of screening guidelines for non-AIDS-defining malignancies: evolving issues in the era of highly active antiretroviral therapy. AIDS Rev 2012;14(1):3-16. [PMID: 22297500

Weyers S, De Sutter P, Hoebeke S, et al. Gynaecological aspects of the treatment and follow-up of transsexual men and women. Facts Views Vis Obgyn 2010;2(1):35-54. [PMID: 25206965

Presentation and Diagnosis of HPV Infection

Reviewed and updated: Meera Shah, MD, MPH, MS, AAHIVS, with the Medical Care Criteria Committee; November 4, 2022

RECOMMENDATIONS
Presentation and Diagnosis of HPV Infection
  • Clinicians with limited expertise should refer patients with abnormal anogenital physical findings, such as warts, hypopigmented or hyperpigmented plaques/lesions, lesions that bleed, or any other lesions of uncertain etiology, for expert evaluation, which may include colposcopy, HRA, or biopsy. (A3)
  • Clinicians should maintain a low threshold for obtaining biopsies of lesions that are atypical in appearance; condylomatous; hypopigmented, hyperpigmented, or variegated; or that fail to respond to standard treatment. (A3)
  • Clinicians should conduct or refer patients with abnormal cervical or anal cytology results for colposcopy, HRA, or biopsy as recommended in the NYSDOH AI guidelines Screening for Cervical Dysplasia and Cancer in Adults With HIV and Screening for Anal Dysplasia and Cancer in Adults With HIV. (A3)
  • Clinicians should refer individuals with visible urethral lesions to a urologist experienced in HPV biopsy and diagnosis. (A3)
  • Clinicians should diagnose, treat, and follow up on HPV-related lesions in patients with HIV in consultation with a clinician experienced in the management of HPV and HIV. (A3)

———
Abbreviations: HPV, human papillomavirus; HRA, high-resolution anoscopy.

Diagnosis of external condylomata acuminata is often made based on clinical appearance. The appearance of warts varies. Condylomata acuminata (genital warts) can be smooth and skin-colored or hyperpigmented papules or plaques that may be flat, hyperkeratotic, nodular, or exophytic. Symptoms may be absent or may include itching, bleeding, burning, and discomfort. Warts on the external genitalia and the cervix are commonly flat, plaque-like lesions but may also be exophytic and visible to the naked eye. Cervical lesions are best visualized by colposcopy. Penile lesions can occur along the shaft but may also occur along the penile urethra and be hidden from view.

Small external lesions are often treated without biopsy. Lesions that are atypical or variegated in color or shape require biopsy to exclude squamous intraepithelial lesions (SILs) or cancer. Clinicians should maintain a low threshold for obtaining biopsies of the following, which may indicate precancerous or cancerous lesions: atypical-appearing lesions; pigmented, internal, or condylomatous lesions; rapidly growing lesions; or lesions that fail to respond to standard treatment.

Manifestations of HPV infection in individuals with HIV infection may include the following [Wang and Palefsky 2019; Liu, et al. 2018; Clifford, et al. 2017; Palefsky 2017; Lillo, et al. 2001; Minkoff, et al. 2001; Palefsky, et al. 2001a; Palefsky, et al. 2001b; Frisch, et al. 2000; Palefsky, et al. 1998]:

  • Condylomata acuminata, anal SILs, anal intraepithelial neoplasia, cervical SILs, and cervical intraepithelial neoplasia have all been reported to occur more frequently in people with HIV.
  • With increased immunosuppression, there is evidence for increased risk of persistent and recurrent HPV infection and disease of the anal and genital tracts; decreased rates of spontaneous disease regression; increased severity of HPV disease; anal SILs and cervical SILs; and development of condylomata acuminata.
  • HPV infection may be more difficult to treat and more likely to recur with advanced immunosuppression.
  • Patients with more advanced immunosuppression have an increased relative risk of developing HPV-related invasive anogenital cancers.
resources

For images of the clinical manifestations of HPV, see the following:

Data are mixed regarding the contribution of HIV-related immune suppression to the relapse and progression of HPV disease and whether antiretroviral therapy (ART)-mediated immune reconstitution can lead to regression of SIL associated with HPV infection [Blitz, et al. 2013; Piketty, et al. 2013; Adler 2010]. Although there are cases of involution of mucocutaneous warts after initiation of ART, the prevalence or course of anogenital HPV disease is not altered significantly by ART [Lofgren, et al. 2015; Adler 2010].

KEY POINTS
  • Cervical and anogenital symptoms of HPV-associated disease include itching, bleeding, pain, or spotting after sexual intercourse. Consider HPV-associated disease in the differential diagnosis when symptoms are present.
  • Failure to correctly diagnose precancerous or cancerous HPV-related disease in a timely manner can delay therapy and possibly lead to mortality. Therefore, maintain a low threshold for obtaining biopsies of lesions that are atypical in appearance, are condylomatous, have variegated pigmentation, or that fail to respond to standard treatment.
References

Adler DH. The impact of HAART on HPV-related cervical disease. Curr HIV Res 2010;8(7):493-497. [PMID: 20946095

Blitz S, Baxter J, Raboud J, et al. Evaluation of HIV and highly active antiretroviral therapy on the natural history of human papillomavirus infection and cervical cytopathologic findings in HIV-positive and high-risk HIV-negative women. J Infect Dis 2013;208(3):454-462. [PMID: 23624362]

Clifford GM, Tully S, Franceschi S. Carcinogenicity of human papillomavirus (HPV) types in HIV-positive women: a meta-analysis from HPV infection to cervical cancer. Clin Infect Dis 2017;64(9):1228-1235. [PMID: 28199532

Frisch M, Biggar RJ, Goedert JJ. Human papillomavirus-associated cancers in patients with human immunodeficiency virus infection and acquired immunodeficiency syndrome. J Natl Cancer Inst 2000;92(18):1500-1510. [PMID: 10995805

Lillo FB, Ferrari D, Veglia F, et al. Human papillomavirus infection and associated cervical disease in human immunodeficiency virus-infected women: effect of highly active antiretroviral therapy. J Infect Dis 2001;184(5):547-551. [PMID: 11494160

Liu G, Sharma M, Tan N, et al. HIV-positive women have higher risk of human papilloma virus infection, precancerous lesions, and cervical cancer. AIDS 2018;32(6):795-808. [PMID: 29369827

Lofgren SM, Tadros T, Herring-Bailey G, et al. Progression and regression of cervical pap test lesions in an urban AIDS clinic in the combined antiretroviral therapy era: a longitudinal, retrospective study. AIDS Res Hum Retroviruses 2015;31(5):508-513. [PMID: 25693769]

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):2157-2164. [PMID: 11684935

Palefsky JM. Human papillomavirus-associated anal and cervical cancers in HIV-infected individuals: incidence and prevention in the antiretroviral therapy era. Curr Opin HIV AIDS 2017;12(1):26-30. [PMID: 27828801

Palefsky JM, Holly EA, Hogeboom CJ, et al. Virologic, immunologic, and clinical parameters in the incidence and progression of anal squamous intraepithelial lesions in HIV-positive and HIV-negative homosexual men. J Acquir Immune Defic Syndr Hum Retrovirol 1998;17(4):314-319. [PMID: 9525431

Palefsky JM, Holly EA, Ralston ML, et al. Effect of highly active antiretroviral therapy on the natural history of anal squamous intraepithelial lesions and anal human papillomavirus infection. J Acquir Immune Defic Syndr 2001a;28(5):422-428. [PMID: 11744829

Palefsky JM, Holly EA, Ralston ML, et al. Prevalence and risk factors for anal human papillomavirus infection in human immunodeficiency virus (HIV)-positive and high-risk HIV-negative women. J Infect Dis 2001b;183(3):383-391. [PMID: 11133369

Piketty C, Cochand-Priollet B, Lanoy E, et al. Lack of regression of anal squamous intraepithelial lesions despite immune restoration under cART. AIDS 2013;27(3):401-406. [PMID: 23079803

Wang CJ, Palefsky JM. HPV-associated anal cancer in the HIV/AIDS patient. Cancer Treat Res 2019;177:183-209. [PMID: 30523625

HPV Treatment

Reviewed and updated: Meera Shah, MD, MPH, MS, AAHIVS, with the Medical Care Criteria Committee; November 4, 2022

RECOMMENDATIONS
HPV Treatment
  • Clinicians should not use sinecatechins in patients with HIV. (A3)
  • Clinicians should obtain a biopsy to exclude dysplasia or cancer for condyloma that have not responded to treatment. (A3)
  • Clinicians should switch treatment modalities if biopsy-confirmed warts or condyloma have not improved substantially within 4 months of therapy. (A3)
  • Clinicians should refer patients with lesions that are resistant to topical therapies; that change in appearance; that have ulceration, irregular shape, or variegated pigmentation; or with biopsy-proven dysplasia to clinicians experienced in the management of human papillomavirus (HPV) and HIV. (A3)
  • Clinicians should refer patients with visible urethral lesions to a urologist for treatment. (A3)
  • Clinicians should refer patients with HIV who have anogenital cancer to an oncologist for treatment. (A3)
  • Clinicians should avoid the use of imiquimod in pregnant individuals unless the benefits outweigh the risk. (A3)
  • Clinicians should not use sinecatechins, podophyllin, or podofilox (podophyllotoxin) in pregnant individuals. (A3)

The standard therapeutic approach to treating HPV-related nonmalignant lesions (condyloma/warts) and dysplasia (squamous intraepithelial lesions or above) in individuals with HIV is the same as that for individuals without HIV. Treatment of condyloma is aimed at removing symptomatic visible warts. However, some untreated warts may resolve spontaneously. There has been no evidence that any available treatment regimen eradicates HPV infection. Comparative efficacy trials of the different treatment options for patients with HIV have not been conducted. Treatment of precancerous lesions includes ablation, using cryotherapy or laser, and surgical or laser excision. These procedures should be performed only by experienced clinicians (see the NYSDOH AI guideline Screening for Cervical Dysplasia and Cancer in Adults With HIV for more information).

Cryotherapy, electrocautery, podophyllotoxin, interferon, imiquimod, cidofovir gel, trichloroacetic acid, and bichloroacetic acid have all demonstrated efficacy treating anogenital warts in patients without HIV. In a systematic review and meta-analysis, electrocautery and imiquimod were shown to be efficacious in treating anogenital warts in people with HIV [Werner, et al. 2017]. Controlled studies of other HPV interventions in people with HIV have not been done. Interferon, 5-fluorouracil, and podophyllotoxin are no longer preferred HPV treatments in the primary care setting because of low efficacy and toxicity that may limit their routine use [Lacey, et al. 2013]. The safety and efficacy of sinecatechins have not been evaluated in individuals with HIV and therefore should not be used [FDA 2007].

There are limited data on imiquimod use in pregnancy, but animal data suggest low risk of harm [Workowski, et al. 2021]. This drug can be used during pregnancy if no other options, including waiting until after delivery, are available. Because of a lack of safety data, podophyllin should not be used during pregnancy. Podofilox (podophyllotoxin) is contraindicated in pregnancy [Briggs, et al. 2017].

Data on treating HPV lesions of the neovagina, whether penile or colonic in origin, are limited to case reports and small case series. Standard, care provider-applied approaches to treatment should be used [Labanca and Mañero 2017; van der Sluis, et al. 2016; Matsuki, et al. 2015; Wasef, et al. 2005; Liguori, et al. 2004; Fiumara and Di Mattia 1973].

Clinicians often report poor clearance rates after therapy in patients with HIV [Richel, et al. 2013]. More than one application of therapy, more than one method of treatment (e.g., topical imiquimod followed by cryotherapy), or longer duration of treatment is often needed. Treatment length may vary, and frequent visits (as often as biweekly) are necessary to assess lesion regression and adverse effects. Topical treatments may cause adverse effects such as irritation and a burning sensation, which may affect treatment adherence. The response to treatment and its adverse effects should be evaluated throughout the course of therapy. The treatment approach may need to be changed if a patient has not improved substantially after standard therapy. There are no data available regarding effects of HPV treatment on HPV transmissibility.

When deciding whether to treat a patient with HIV for anogenital warts or refer the patient to a specialist, clinicians should consider their own experience and available resources, diagnostic certainty, anatomic site of lesions, potential adverse effects of treatment, and the patient’s ability to adhere to treatment.

The below table lists available treatment options for condyloma for patients with HIV.

Table: Available Treatment Options for Anogenital Condyloma for Patients With HIV [a] 
Download PDF
Condyloma Type Treatment [b,c] Comments
Anogenital condyloma
  • Cryotherapy with liquid nitrogen or cryoprobe
  • Surgical excision
  • TCA or BCA 80%–90% solution [d]

Patient self-administered treatments:

  • Imiquimod 3.75% or 5% cream [e]
  • Podofilox 0.5% solution or gel [e]
  • Use for external anogenital warts, including warts on penis, groin, scrotum, vulva, perineum, external anus, and perianus.
  • Patients with external anal or perianal warts may also have intra-anal warts and therefore might benefit from inspection of the anal canal by digital examination or anoscopy (standard or high resolution).
  • Imiquimod may weaken condoms and vaginal diaphragms.
Urethral meatus condyloma
  • Cryotherapy with liquid nitrogen
  • Surgical excision
Vaginal condyloma
  • Cryotherapy with liquid nitrogen
  • Surgical excision
  • TCA or BCA 80%–90% solution [d]
Cryoprobe use in the vagina is not recommended because of the risk of vaginal perforation and fistula formation.
Cervical condyloma
  • Cryotherapy with liquid nitrogen
  • Surgical excision
  • TCA or BCA 80%–90% solution [d]
  • Management of cervical warts should include consultation with a specialist.
  • For patients who have exophytic cervical warts, a biopsy evaluation to exclude high-grade squamous intraepithelial lesions must be performed before treatment is initiated.
Intra-anal condyloma
  • Cryotherapy with liquid nitrogen
  • Surgical excision
  • TCA or BCA 80%–90% solution [d]
Management of intra-anal warts should include consultation with a colorectal specialist.
Neovaginal condyloma [f,g]
  • Cryotherapy with liquid nitrogen or cryoprobe
  • Surgical excision
  • TCA or BCA 80%–90% [d]

Patient self-administered treatments:

  • Imiquimod 3.75% or 5% cream [e]
  • Podofilox 0.5% solution or gel [e]
Imiquimod may weaken condoms and vaginal diaphragms.

Abbreviations: BCA, bichloroacetic acid; TCA, trichloroacetic acid.

Notes:

  1. Adapted from [Workowski, et al. 2021] unless otherwise noted.
  2. Sinecatechins should not be used in any individual with HIV because safety and efficacy data do not exist [FDA 2007].
  3. Podophyllin resin is no longer recommended because of the number of safer options available.
  4. TCA or BCA can be used to treat small external warts during pregnancy but may not be as effective.
  5. Imiquimod, podophyllin, podofilox (podophyllotoxin), and sinecatechins should not be used in pregnant individuals [Briggs, et al. 2017].
  6. If the neovagina was made using sigmoid colon tissue, treatments for intra-anal condyloma should be used.
  7. [Labanca and Mañero 2017; van der Sluis, et al. 2016; Matsuki, et al. 2015; Wasef, et al. 2005; Liguori, et al. 2004; Fiumara and Di Mattia 1973]
References

Briggs GG, Freeman RK, Yaffe SJ. 2017. Drugs in pregnancy and lactation: A reference guide to fetal and neonatal risk. Williams & Wilkins. https://books.google.com/books?id=o3ymMgEACAAJ

FDA. Veregen (sinecatechins) ointment, 15%. 2007 Dec. https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/021902s002lbl.pdf [accessed 2022 Oct 17]

Fiumara NJ, Di Mattia A. Gonorrhoea and condyloma acuminata in a male transsexual. Br J Vener Dis 1973;49(5):478-479. [PMID: 4270635

Labanca T, Mañero I. Vulvar condylomatosis after sex reassignment surgery in a male-to-female transsexual: Complete response to imiquimod cream. Gynecol Oncol Rep 2017;20:75-77. [PMID: 28349118

Lacey CJ, Woodhall SC, Wikstrom A, et al. 2012 European guideline for the management of anogenital warts. J Eur Acad Dermatol Venereol 2013;27(3):e263-270. [PMID: 22409368

Liguori G, Trombetta C, Bucci S, et al. Condylomata acuminata of the neovagina in a HIV-seropositive male-to-female transsexual. Urol Int 2004;73(1):87-88. [PMID: 15263800

Matsuki S, Kusatake K, Hein KZ, et al. Condylomata acuminata in the neovagina after male-to-female reassignment treated with CO2 laser and imiquimod. Int J STD AIDS 2015;26(7):509-511. [PMID: 24970474

Richel O, de Vries HJ, van Noesel CJ, et al. Comparison of imiquimod, topical fluorouracil, and electrocautery for the treatment of anal intraepithelial neoplasia in HIV-positive men who have sex with men: an open-label, randomised controlled trial. Lancet Oncol 2013;14(4):346-353. [PMID: 23499546

van der Sluis WB, Buncamper ME, Bouman MB, et al. Symptomatic HPV-related neovaginal lesions in transgender women: case series and review of literature. Sex Transm Infect 2016;92(7):499-501. [PMID: 27013740

Wasef W, Sugunendran H, Alawattegama A. Genital warts in a transsexual. Int J STD AIDS 2005;16(5):388-389. [PMID: 15949073

Werner RN, Westfechtel L, Dressler C, et al. Anogenital warts and other HPV-associated anogenital lesions in the HIV-positive patient: a systematic review and meta-analysis of the efficacy and safety of interventions assessed in controlled clinical trials. Sex Transm Infect 2017;93(8):543-550. [PMID: 28637906

Workowski KA, Bachmann LH, Chan PA, et al. Sexually transmitted diseases treatment guidelines, 2021. MMWR Recomm Rep 2021;70(RR-4):1-187. [PMID: 26042815

Partner Exposure to HIV and HPV

Reviewed and updated: Meera Shah, MD, MPH, MS, AAHIVS, with the Medical Care Criteria Committee; November 4, 2022

RECOMMENDATION
Partner Exposure to HIV and HPV
  • When a patient with HIV is diagnosed with human papillomavirus (HPV), clinicians should advise the patient to encourage sex partners to seek evaluation for possible exposure to both HPV and HIV. (A3)

Treatment of lesions solely for the prevention of future transmission cannot be recommended because the value of treatment in reducing infectivity is not known. However, sex partners of patients who have genital lesions might benefit from counseling and examination to assess the presence of genital warts and HPV-related dysplasia. Sex partners should also be evaluated for other sexually transmitted infections (STIs), including HIV, because HPV disease is transmitted sexually [Workowski, et al. 2021].

Clinicians should inform patients that any sex partner who does not have confirmed HIV infection should have routine HIV testing for early identification of HIV acquisition. If a patient with an HIV exposure presents within 36 hours, evaluation for non-occupational post-exposure prophylaxis (PEP) should occur. When possible, onsite availability of HIV testing and STI treatment for partners is ideal because it may increase the likelihood that partners will receive timely access to HIV testing and appropriate treatment, including HIV post-exposure prophylaxis and treatment for the STI as needed (see the NYSDOH AI guideline PEP to Prevent HIV Infection). Such strategies may also increase identification of individuals who require ongoing medical care. Partner education about reducing high-risk sexual behaviors, including counseling about the use of male/insertive and female/receptive condoms and making condoms visibly available in the clinic, may help further decrease the risk of transmission of both HIV and other STIs. Patients who remain at high risk of exposure after completing a course of non-occupational PEP (nPEP) and who are negative for HIV at the time of the 4-week test should be offered pre-exposure prophylaxis (PrEP), to begin immediately after the last dose of nPEP (see the NYSDOH AI guideline PrEP to Prevent HIV and Promote Sexual Health). Patient education about undetectable=untransmittable (U=U) as an HIV prevention strategy should stress that an undetectable HIV viral load prevents only the sexual transmission of HIV (see the NYSDOH AI resource U=U Guidance for Implementation in Clinical Settings). 

NEW YORK STATE LAW
  • New York State Public Health Law requires that medical providers talk with individuals with HIV about their options for informing their sex partners that they may have been exposed to HIV, including the free, confidential partner notification assistance offered by the NYSDOH and New York City Department of Health and Mental Hygiene.

The NYSDOH Partner Services program provides assistance to individuals with HIV and care providers who would like help notifying a patient’s sex partner(s) of possible exposure to HIV, chlamydia, gonorrhea, or syphilis. Available options for partner notification include anonymous notification from the local health department, dual disclosure (patient disclosure with the help of Partner Services staff), and self-disclosure. Partner Services staff within local health departments work with patients to develop a plan to notify their partners, whether that plan includes staff notifying potentially exposed partners anonymously or helping patients who choose to tell their partners on their own develop a notification plan and strategy.

KEY POINTS
  • The local health department may contact a sex partner confidentially about a potential HIV exposure and treatment options.
  • Counsel patients about partner notification, risk reduction, and safer sex practices.
Reference

Workowski KA, Bachmann LH, Chan PA, et al. Sexually transmitted diseases treatment guidelines, 2021. MMWR Recomm Rep 2021;70(RR-4):1-187. [PMID: 26042815

All Recommendations

Reviewed and updated: Meera Shah, MD, MPH, MS, AAHIVS, with the Medical Care Criteria Committee; November 4, 2022

ALL RECOMMENDATIONS: PREVENTION AND MANAGEMENT OF HUMAN PAPILLOMAVIRUS INFECTION IN ADULTS WITH HIV
HPV Prevention
  • Given the increased lifetime risk of persistent human papillomavirus (HPV) infection and increased prevalence of HPV-related cancers, clinicians should recommend the 9-valent HPV vaccine 3-dose series at 0, 2, and 6 months to all individuals with HIV who are 9 to 45 years old regardless of CD4 cell count, prior cervical or anal screening results, HPV test results, HPV-related cytologic changes, or other history of HPV-related lesions. (A3)
Cervical and Anal Cancer Screening
  • Clinicians should perform cervical and anal cytologic screening for individuals with HIV, regardless of their human papillomavirus (HPV) vaccination status, as recommended in the NYSDOH AI guidelines Screening for Cervical Dysplasia and Cancer in Adults With HIV and Screening for Anal Dysplasia and Cancer in Adults With HIV. (A3)
  • Clinicians should examine the neovagina in transgender women who have undergone vaginoplasty to assess for visible HPV lesions at baseline and during the annual comprehensive physical examination; examination can be done using an anoscope, a small vaginal speculum, or a nasal speculum. (A3)
  • At each routine monitoring visit, clinicians should ask all patients about sexual behaviors and new sex partners to assess for risk behaviors that require repeat or ongoing screening. (A3)
Presentation and Diagnosis of HPV Infection
  • Clinicians with limited expertise should refer patients with abnormal anogenital physical findings, such as warts, hypopigmented or hyperpigmented plaques/lesions, lesions that bleed, or any other lesions of uncertain etiology, for expert evaluation, which may include colposcopy, HRA, or biopsy. (A3)
  • Clinicians should maintain a low threshold for obtaining biopsies of lesions that are atypical in appearance; condylomatous; hypopigmented, hyperpigmented, or variegated; or that fail to respond to standard treatment. (A3)
  • Clinicians should conduct or refer patients with abnormal cervical or anal cytology results for colposcopy, HRA, or biopsy as recommended in the NYSDOH AI guidelines Screening for Cervical Dysplasia and Cancer in Adults With HIV and Screening for Anal Dysplasia and Cancer in Adults With HIV. (A3)
  • Clinicians should refer individuals with visible urethral lesions to a urologist experienced in HPV biopsy and diagnosis. (A3)
  • Clinicians should diagnose, treat, and follow up on HPV-related lesions in patients with HIV in consultation with a clinician experienced in the management of HPV and HIV. (A3)
HPV Treatment
  • Clinicians should not use sinecatechins in patients with HIV. (A3)
  • Clinicians should obtain a biopsy to exclude dysplasia or cancer for condyloma that have not responded to treatment. (A3)
  • Clinicians should switch treatment modalities if biopsy-confirmed warts or condyloma have not improved substantially within 4 months of therapy. (A3)
  • Clinicians should refer patients with lesions that are resistant to topical therapies; that change in appearance; that have ulceration, irregular shape, or variegated pigmentation; or with biopsy-proven dysplasia to clinicians experienced in the management of human papillomavirus (HPV) and HIV. (A3)
  • Clinicians should refer patients with visible urethral lesions to a urologist for treatment. (A3)
  • Clinicians should refer patients with HIV who have anogenital cancer to an oncologist for treatment. (A3)
  • Clinicians should avoid the use of imiquimod in pregnant individuals unless the benefits outweigh the risk. (A3)
  • Clinicians should not use sinecatechins, podophyllin, or podofilox (podophyllotoxin) in pregnant individuals. (A3)
Partner Exposure to HIV and HPV
  • When a patient with HIV is diagnosed with human papillomavirus (HPV), clinicians should advise the patient to encourage sex partners to seek evaluation for possible exposure to both HPV and HIV. (A3)

———
Abbreviations: HPV, human papillomavirus; HRA, high-resolution anoscopy.

Guideline Information and Updates

Guideline Information
Intended users Clinicians in New York State who provide care to individuals with HIV
Last reviewed and updated November 4, 2022; Meera Shah, MD, MPH, MS, AAHIVS
Original lead author Medical Care Criteria Committee
Original publication May 2013
Writing group Steven M. Fine, MD, PhD; Rona M. Vail, MD; Samuel T. Merrick, MD; Asa E. Radix, MD, MPH, PhD; Charles J. Gonzalez, MD; Christopher J. Hoffmann, MD, MPH
Committee Medical Care Criteria Committee
Developer and funding New York State Department of Health AIDS Institute (NYSDOH AI)
Development See Guideline Development and Recommendation Ratings, below.
Peer reviewers
  • Gregg Alleyne, MD, FACOG, Drexel University College of Medicine
  • John Clark, MD, ABOG, Columbia University
Updates
November 4, 2022

Meera Shah, MD, MPH, MS, AAHIVS, with the MCCC:

July 11, 2018 Gina Brown, MD, with the MCCC: Comprehensive update
Guideline Development: New York State Department of Health AIDS Institute Clinical Guidelines Program
Developer New York State Department of Health AIDS Institute (NYSDOH AI) Clinical Guidelines Program
Funding Source NYSDOH AI
Program Manager

Clinical Guidelines Program, Johns Hopkins University School of Medicine, Division of Infectious Diseases. See Program Leadership and Staff.

Mission To produce and disseminate evidence-based, state-of-the-art clinical practice guidelines that establish uniform standards of care for practitioners who provide prevention or treatment of HIV, viral hepatitis, other sexually transmitted infections, and substance use disorders for adults throughout New York State in the wide array of settings in which those services are delivered.
Expert Committees

The NYSDOH AI Medical Director invites and appoints committees of clinical and public health experts from throughout NYS to ensure that the guidelines are practical, immediately applicable, and meet the needs of care providers and stakeholders in all major regions of NYS, all relevant clinical practice settings, key NYS agencies, and community service organizations.

Committee Structure
  • Leadership: AI-appointed chair, vice chair(s), chair emeritus, clinical specialist(s), JHU Guidelines Program Director, AI Medical Director, AI Clinical Consultant, AVAC community advisor
  • Contributing members
  • Guideline writing groups: Lead author, coauthors if applicable, and all committee leaders
Conflicts of Interest Disclosure and Management
  • Annual disclosure of financial relationships with commercial entities for the 12 months prior and upcoming is required of all individuals who work with the guidelines program, and includes disclosure for partners or spouses and primary professional affiliation.
  • The NYSDOH AI assesses all reported financial relationships to determine the potential for undue influence on guideline recommendations and, when indicated, denies participation in the program or formulates a plan to manage potential conflicts.
  • Disclosures are listed for each committee member.
Evidence Collection and Review
  • Literature search and review strategy is defined by the guideline lead author based on the defined scope of a new guideline or update.
  • A comprehensive literature search and review is conducted for a new guideline or an extensive update using PubMed, other pertinent databases of peer-reviewed literature, and relevant conference abstracts to establish the evidence base for guideline recommendations.
  • A targeted search and review to identify recently published evidence is conducted for guidelines published within the previous 3 years.
  • Title, abstract, and article reviews are performed by the lead author. The JHU editorial team collates evidence and creates and maintains an evidence table for each guideline.
Recommendation Development
  • The lead author drafts recommendations to address the defined scope of the guideline based on available published data.
  • Writing group members review the draft recommendations and evidence and deliberate to revise, refine, and reach consensus on all recommendations.
  • When published data are not available, support for a recommendation may be based on the committee’s expert opinion.
  • The writing group assigns a 2-part rating to each recommendation to indicate the strength of the recommendation and quality of the supporting evidence. The group reviews the evidence, deliberates, and may revise recommendations when required to reach consensus. 
Review and Approval Process
  • Following writing group approval, draft guidelines are reviewed by all contributors, program liaisons, and a volunteer reviewer from the AI Community Advisory Committee.
  • Recommendations must be approved by two-thirds of the full committee. If necessary to achieve consensus, the full committee is invited to deliberate, review the evidence, and revise recommendations when required.
  • Final approval by the committee chair and the NYSDOH AI Medical Director is required for publication.
External Reviewers
  • External peer reviewers recognized for their experience and expertise review guidelines for accuracy, balance, clarity, and practicality and provide feedback.
  • Peer reviewers may include nationally known experts from outside of New York State.
Update Process
  • JHU editorial staff ensure that each guideline is reviewed and determined to be current upon the 3-year anniversary of publication; guidelines that provide clinical recommendations in rapidly changing areas of practice may be reviewed annually. Published literature is surveilled to identify new evidence that may prompt changes to existing recommendations or development of new recommendations.
  • If changes in the standard of care, newly published studies, new drug approval, new drug-related warning, or a public health emergency indicate the need for immediate change to published guidelines, committee leadership will make recommendations and immediate updates.
  • All contributing committee members review and approve substantive changes to, additions to, or deletions of recommendations; JHU editorial staff track, summarize, and publish ongoing guideline changes.
Recommendation Ratings Scheme
Strength Quality of Evidence
Rating Definition Rating Definition
A Strong 1 Based on published results of at least 1 randomized clinical trial with clinical outcomes or validated laboratory endpoints.
B Moderate * Based on either a self-evident conclusion; conclusive, published, in vitro data; or well-established practice that cannot be tested because ethics would preclude a clinical trial.
C Optional 2 Based on published results of at least 1 well-designed, nonrandomized clinical trial or observational cohort study with long-term clinical outcomes.
  2† Extrapolated from published results of well-designed studies (including nonrandomized clinical trials) conducted in populations other than those specifically addressed by a recommendation. The source(s) of the extrapolated evidence and the rationale for the extrapolation are provided in the guideline text. One example would be results of studies conducted predominantly in a subpopulation (e.g., one gender) that the committee determines to be generalizable to the population under consideration in the guideline.
3 Based on committee expert opinion, with rationale provided in the guideline text.