Bottoms UP HIV and Anal Cancer from Screening to Prevention

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1 Bottoms UP HIV and Anal Cancer from Screening to Prevention Paul MacPherson PhD, MD, FRCPC Associate Professor Division of Infectious Diseases University of Ottawa

2 The New Reality Normal or near-normal immune function For those diagnosed at age 20, life expectancy is now 65.8 years. May et al. (2010) Tenth International Congress on Drug Therapy in HIV Infection.

3 With longer life expectancy, we are starting to see new problems not encountered previously in the HIV population 1. Cardiovascular disease 2. Cancers, and in particular anal cancer

4 Anal Cancer in Ontario Age- & Sex-Adjusted Incidence, /100, /100,000 Tinmouth J, et al. Am J Gastro 2006;101(9):S419.

5 Anal Cancer: Incidence Relatively uncommon Has been increasing over the past 30 years Incidence per 100,000 person-yrs: General population 2 MSM 35 HIV+ MSM 100 Piketty, C. et al. AIDS, 2008; 22: D Souza, G. et al. JAIDS 2008; 48: Patel, P. et al. Ann Inten Med 2008;

6 Anal Cancer Often no symptoms Most people come to medical attention too late Bleeding is most common first sign Often incorrectly attributed to hemorrhoids

7 Anal Cancer: Survival ( ) Tinmouth J, et al. Am J Gastro 2006;101(9):S419.

8 Similar Malignancies in Quebec 5-Year Survival Louchini et al. Chronic Dis Canada, 2008

9 Anal Cancer This is a problem: 14x higher incidence in MSM 50x higher incidence in HIV+ MSM Survival in men is very poor

10 What causes anal cancer?

11 Human Papilloma Virus Most common viral STI 75% of women 80-90% MSM

12 Genital HPV Over 100 different genotypes of HPV HPV 6, 11, 42, 43, 44 and 54 are associated with genital warts HPV 16, 18, 31 33, 35, 39, 45, 51, 52, 54, 56, 66 and 68 are associated with oropharyngeal, vulvovaginal, cervical, penile and rectal carcinomas

13 HPV is very common among MSM HIV+ HIV- HPV+ (PCR) 93% 61% Multiple HPV 73% 23% HPV-16 35% 9% High risk HPV 80% 29% Palefsky JID 1998

14 Papillomavirus Infection Viral assembly and shedding High level replication Cell transformation Infects basal cells Maintenance replication

15 Human Papilloma Virus

16 Development of anal cancer Infected cells slowly progress through several stages to become malignant: ASCUS Low grade AIN 1 AIN 2 High grade AIN3 Carcinoma in situ Invasive carcinoma HPV is necessary but not sufficient. Other factors required for transformation to cancer

17 Anal Cancer Screening

18 Screening for Anal Cancer ~ Analogy to cervical cancer ~ Cervical cancer in women: 40/100,000 annual incidence (pre 60s) Anal cancer in HIV+ MSM: 100/100,000 annual incidence ROUTINE CERVICAL PAPs with ablative treatment of dysplasia ANAL PAP SMEARS with ablative treatment of dysplasia 8/100,000 annual incidence?annual incidence Jill Tinmouth, 2003

19 Screening for anal cancer Similar to screening for cervical cancer: use of the anal Pap smear follow-up abnormal cytology with high resolution anoscopy (HRA)

20 Anal Pap Test

21 Anal Pap Test Anal LSIL Low grade squamous intraepithelial lesion Anal HSIL High grade squamous intraepithelial lesion

22 Anal Pap Test Sensitivity Specificity HIV+ 81% 63% HIV- 50% 92% Palefsky et al JAIDS 1997 Same Sen & Spec as with the cervical Pap The success of the Pap test is with repeat screening

23 High Resolution Anoscopy The following slides are courtesy of Drs Irv Salit and Jill Tinmouth, Univ of Toronto

24 Anoscopy: Normal

25 Anoscopy: Normal

26 Anoscopy: Low Grade

27 Anoscopy: High Grade

28 Anoscopy: High Grade

29 Anoscopy High Grade

30 Anal Biopsies Low Grade AIN Normal epitheilium High Grade AIN

31 Recommendation Palefsky, Sem Onc 2000

32 Treatment

33 Trichloroacetic acid Applied directly to the lesion Treated at 2 to 3 week intervals for up to 4 treatments Ulceration occurs that re-epithelializes Mild discomfort Singh et al JAIDS 2009; 52: HIV(+) and 19 HIV(-) men with high grade lesions 32% cleared to no lesions 71% cleared to no or low grade lesions

34 Infra-red Coagulation Delivers a 1.5 second pulse of infra-red light that causes coagulative necrosis Requires local anesthetic Patients will experience mild to moderate discomfort for a few days to a week particularly with BM Minor bleeding can occur Stier et al. JAIDS 2008; Goldstone et al. DCR, % clearance of treated lesion 60-80% HIV+ patients have recurrence of HSIL lesion

35 Why screen for anal cancer?

36 Five-year survival following diagnosis: Stage I: 71% Stage II: 64% Stage III: 45% Stage IV: 21% There is a clear mortality benefit to early detection.

37 UCSF Experience 51 patients with anal carcinoma in situ 41 patients were HIV+ All underwent surgical resection of the carcinoma in situ and then were followed with anoscopy and treatment of any new high grade lesions Outcomes: No patients died No patients required colostomies 88% were spared chemo and radiation

38 Pineda et al. Dis Colon Rectum, men and 39 women (74% HIV+) All taken to the operating room for surgical excision of high grade anal lesions Some were simply followed Some received regular anoscopy and out-patient treatment of recurrent high grade lesions with IRC

39 Pineda et al. Dis Colon Rectum, No intervention: 34% had to return to the OR Regular anoscopy and IRC 8% had to return to the OR Anoscopy and IRC lead to a 75% reduction in the need for repeat surgery thus reducing morbidity and cost.

40 HPV Vaccine Quadrivalent vaccine in men: 90.4% efficacy for genital lesion due to HPV 6, 11, 16 or 18 (per-protocol analysis; NEJM 2011) Bivalent vaccine reduced incidence of anal HPV infection in women (Lancet, 2011) Vaccine FDA approval for prevention of anal cancer in Dec 2010.

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42 602 men who have sex with men Inclusion criteria: Age years Fewer than 5 lifetime sexual partners Exclusion criteria: HIV-positive Vaccine (qhpv) at 0, 2 and 6 months

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44 HPV Vaccine Clear efficacy of HPV vaccine in reducing genital warts and AIN lesions Who should be vaccinate? When should we vaccinate? Should we vaccinate after people have become sexually active?

45 Make sure someone is watching your behind