Update on Anal HPV. Medical Management of AIDS. December 9, Joel Palefsky Department of Medicine University of California, San Francisco

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1 Update on Anal HPV Medical Management of AIDS December 9, 2017 Joel Palefsky Department of Medicine University of California, San Francisco Disclosures Merck and Co- research and travel support Antiva Biosciences- consultant and research support Agenovir- consultant, stock options Ubiome- stock options Joel Palefsky, M.D. Outline Scope of the problem What s new in primary prevention What s new in secondary prevention What s new in treatment

2 Anal Cancer Incidence Is Increasing In Males and Females in Many Countries Age-standardized incidence rates of anal squamous cell carcinoma by sex Females Males Incidence per 100,000 Year ( ) Based on data from the International Agency for Research on Cancer s Cancer Incidence in Five Continents series. 1. Islami F, et al. Int J Epidemiol Oct 27. pii: dyw276. [Epub ahead of print]. 6 Anal cancer incidence Anal cancer incidence by age-women accessed

3 Anal cancer incidence by age- men People living with HIV/AIDS are living into older ages In 2015 it was estimated that over half of people living with HIV/AIDS (PLWHA) in the U.S. were over the age of 50 years The 2011 CDC HIV Surveillance report estimates that over 311,000 PLWHA were over 50 years old in accessed Luther VP, Wilkin AM. HIV infection in older adults. Clinics in geriatric medicine. Aug 2007;23(3): , vii. PLWHA may be aging prematurely Anal cancers are diagnosed earlier in HIV+ individuals Several illnesses associated with advanced age are now common among HIV-infected individuals receiving ART cardiovascular disease (CVD), liver disease, renal disease, diabetes neurocognitive decline and a number of cancers Shiels M et al. Clin Infect Dis. 2017; 64:

4 HPV-related cancer pre-art HPV HIV Infection HPV HPV Normal Immune suppression Death (Pre-ART) Anal cancer rates in North American AIDS Cohort Collaboration on Research and Design) (NA-ACCORD) Incidence/100,000 (85% CI) HIV-infected MSM 131 ( ) MSW 46 (25-77) Women 30 (17-50) Anogenital disease LSIL Genetic changes HSIL Cancer Silverberg M et al. CID 2012; 54: Calendar trends in standardized incidence ratios for selected cancers in HIV-infected people Non-AIDS-defining cancers Hernandez-Ramirez R. Published online August 10, Robbins H et al. AIDS March 27; 28(6): Joel Palefsky, M.D.

5 Distribution of cancers over time The future of HPV-related cancer in HIV-infected men and women Shiels MS et al. J Natl Cancer Inst 2011;103: Park LS et al, AIDS 2016, 30: Standardized incidence ratios for cancer in HIV-infected people, Future indicators Anal HPV infection Anal HSIL Lung: 2475 cases Prostate: 1522 cases Hernandez-Ramirez R. Published online August 10, doi org/ /S (17)

6 Prevalence of anal HPV among MSM Population-based data Prevalence, % HPV HPV-HR Anal and cervical HPV infection in HIV-positive women and HIV-negative women at high risk of HIV infection Percent Anal Cervical All participants HIV-negative participants HIV-positive participants 0 HIV- HIV+ CD4 >500 HIV+ CD HIV+ CD4 <200 Chin-Hong et al. Ann Int Med. 2008;149; Palefsky JM et al. J Infect Dis. 2001;183: Prevalence of AIN among MSM Population-based data Prevalence, % All participants HIV-negative participants HIV-positive participants Chin-Hong et al. Ann Int Med. 2008;149; Conley et al. JID 2010; 202:

7 High prevalence of anal HSIL in HIV+ women The nonavalent HPV vaccine AMC-084- nearly 30% of HIV+ women Stier EA et al. Presented at International Anal Neoplasia Society (IANS) Scientific Meeting., San Francisco, CA. November 11-13, Schiller J. Lancet Oncol 2015;16(5):e New ACIP recommendations for HPV vaccine For males and females: two injections at least 6 months apart if starting at age 14 or less Three injections at 0,1-2 and 6 months if: 15 or older HIV-positive or otherwise immunosuppressed One dose under investigation!

8 Estimated Vaccination Coverage Among Adolescents Aged years, NIS-Teen, United States, Percent vaccinated (%) Routine HPV Routine HPV 100 recommendation recommendation for females for males 90 1 Tdap 80 1 Men ACWY 70 1 HPV (F) HPV (M) 40 3 HPV (F) 30 3 HPV (M) Survey year F=female; M=male; MenACWY=meningococcal vaccine for serogroups A, C, W, or Y. NIS=National Immunization Survey; Tdap=Tetanus, Diphtheria, Pertussis. 1. Markowitz L et al. Presented at the 31 st Papillomavirus Conference, 28 February 4 March 2017, Cape Town, South Africa. 2 Population effects of HPV vaccination 15-42% reduction in CIN 2+ in Denmark compared with agematched cohort Within 4 years of vaccination 56% reduction in prevalence of HPV 6, 11, 16 and 18 in adolescent females 20 studies summarized in a meta-analysis In countries with >50% vaccine uptake: 68% reduction in HPV 16 and 18 61% reduction in genital warts Drolet M. Lancet Infec Dis 2015;15: Baldur-Felslov B. Cancer Causes Control 2014;25: Markowitz LE I Infec Dis 2013;208: Changes in anogenital wart diagnosis 4 years after the introduction of qhpv vaccine Girls and women, with high female Girls and women, with low female vaccination coverage ( 50%) vaccination coverage (<50%) High resolution anoscopy (HRA) Boys and men, with low female Boys and men, with high female vaccination coverage (<50%) vaccination coverage ( 50%) Boys and men, with high female vaccination coverage ( 50%) HRA is an officebased procedure examining the anus, anal canal and perianus using a colposcope or operating microscope with 5% acetic acid and Lugol s solution Drolet M et l. Lancet Infec Dis 2015; 15(5):

9 Who should be screened? Digital anorectal exam (DARE!) All HIV-positive men regardless of sexual orientation All HIV-negative MSM Women with high-grade cervical or vulvar lesions or cancer All HIV+ women All men and women with perianal condyloma Solid organ transplant recipients Over 25 years if immunosuppressed, inc. HIV Over 40 years if immunocompetent Anal cytology screening for ASIL Challenges of anal cancer screening Screen Normal ASCUS LSIL HSIL Repeat in 12 months (HIV+) Repeat in 2-3 years (HIV-) No lesion seen Anoscopy with biopsy LSIL HSIL Limited sensitivity of anal cytology May be better in HIV+, others? Other diagnostic approaches HPV testing Better sensitivity than cytology Lower specificity and PPV Treat or follow Treat Chin-Hong PV et al. J Infect Dis. 2004;90:

10 HPV testing for anal screening Treatment of HSIL Prevention of anal cancer Relief of symptoms Treatment of anal HSIL Challenging due to multifocal nature, size of lesions Multiple procedures often needed High recurrence rate and incidence of new lesions Therapy is primarily ablative infra-red coagulation/hyfrecation 85% trichloroacetic acid Choice of treatment Location internal or external Size of the lesion or volume of disease Type of lesion: LSIL or HSIL Patient preference and tolerance

11 Hyfrecation/electrocautery Equivalent to IRC in efficacy May be better/faster for perianal disease and bulkier lesions IRC and electrocautery ablation in HIV+ MSM Infra-red coagulation Electrocautery* Number of patients Number of lesions treated % lesions gone after 1 treatment 72% 75% % with metachronous lesions 59% 49% *No statistically significant differences Marks DK et al. J Acquir Immune Defic Syndr 2012; 59: AMC-A01: Funded by NCI and OAR: U01 CA

12 The ANCHOR study Screen >17,385 Randomized controlled trial of 5,058 HIV-infected men and women with anal HSIL comparing treatment with active monitoring over 5 or more years of follow-up Goal is to determine if treating anal HSIL prevents anal cancer Enroll 5,085 Retain for 5 or more years Active Monitoring Treatment Estimate <50 develop cancer Summary Summary Anal cancer is increasing in general population, will remain the most common preventable cancer in HIV+ population Do your DARE! HPV testing will likely be part of screening algorithm The HPV vaccine is highly efficacious and is an Important tool to prevent anal cancer Vaccinate age 26 and under! After age 26= individual decision Anal HSIL can be sought and treated in an effort to reduce the risk of anal cancer Treatment can be challenging Efficacy- in reduction of anal cancer not yet shown- refer to ANCHOR study! ANCHORstudy.org 844-HIV-BUTT

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