Anal Cancer and HPV Related Tumor Prevention

Size: px

Start display at page:

Download "Anal Cancer and HPV Related Tumor Prevention"

Sherman Hunter
5 years ago
Views:

1 Anal Cancer and HPV Related Tumor Prevention Timothy J. Wilkin, MD, MPH Associate Professor of Medicine Weill Cornell Medicine New York, New York Learning Objectives After attending this presentation, learners will be able to describe: Current approaches to anal cancer prevention HPV-associated oropharyngeal cancer Current content on HPV vaccination in HIV-infected populations Slide 3 of 39 Worldwide HPV-related Disease Burden: 630,000 Cancer Cases in Men and Women Penile cancer 1 13,000 Male Female 21,000 Vulvar & vaginal cancer 1 Oropharyngeal cancer 1 28,200 7,500 Oropharyngeal cancer 1 Anal cancer 1 17,000 18,000 Anal cancer 1 530,000 Cervical cancer 1 x 60 fold 9,000,000 High-grade cervical dysplasia 2,3,* 21,900,000 Low-grade cervical dysplasia 2,3, Genital warts 4,5, 17,300,000 14,700,000 Genital warts 4,5, * Estimated 90% of high-grade cervical lesions are HPV related 3 ; Estimated 73% of low-grade cervical lesions are HPV related 3 ; Estimated gender ratio of genital warts: 54% males; 46% females 6 1. Martel C et al. Intl J Cancer. 2017;141: ; 2. World Health Organization.; 3. Guan P, et al. Int J Cancer. 2012;131: ; 4. World Health Organization.; 5. Greer CE, et al. J Clin Microbiol. 1995;33: ; 6. Public Health England.

2 Anal Cancer Anal Cancer in HIV+ people Slide 6 of 39 Schim van der Loff, HIV AIDS Curr Report 2014 Anal Cancer in HIV+ people Cerv CA prior to pap Current cerv CA in US Slide 7 of 39 Schim van der Loff, HIV AIDS Curr Report 2014

3 Natural History of HPV Infection and Potential Progression to Anal Cancer 0 1 Year 0 5 Years 1 20 Years Initial HPV Infection Higher HPV exposure Continuing Infection Anal LSIL Cleared HPV Infection Anal HSIL Invasive Anal Cancer Decreased cellmediated immunity Slide 8 of Pinto AP, Crum CP. Clin Obstet Gynecol. 2000;43: Prevention of Anal Cancer 0 1 Year 0 5 Years 1 20 Years Initial HPV Infection Continuing Infection Anal LSIL Anal HSIL Invasive Anal Cancer Cleared HPV Infection Slide 9 of Pinto AP, Crum CP. Clin Obstet Gynecol. 2000;43: Prevention of Anal Cancer Initial HPV Infection 0 1 Year 0 5 Years 1 20 Years Continuing Infection Anal LSIL Anal HSIL Invasive Anal Cancer Cleared HPV Infection Slide 10 of Pinto AP, Crum CP. Clin Obstet Gynecol. 2000;43:

Anal cancer HRA prevention Learning Curve Goal is to identify pre-cancerous areas of the anus that can be removed to prevent invasive cancer o SCREEN with cytology

chemotherapy and radiation Slide 11 of 39 Richel, AIDS 2014 Which of these is the recommended way to prevent anal cancer according to national guidelines? 1. Treatment of anal condyloma 2.

HPV vaccination of sexually active adults Slide 12 of 39 Anal HSIL in HIV-infected women Anal Histology Anal Cytology n (%) of Total N=255 n (%) of HSIL N=72

4 Anal cancer HRA prevention Learning Curve Goal is to identify pre-cancerous areas of the anus that can be removed to prevent invasive cancer o SCREEN with cytology (or HPV testing *not FDA approved) o DIAGNOSE with High Resolution Anoscopy o TREAT HSIL with ablation or topical therapy Anal cancer is treated with combined chemotherapy and radiation Slide 11 of 39 Richel, AIDS 2014 Which of these is the recommended way to prevent anal cancer according to national guidelines? 1. Treatment of anal condyloma 2. HPV vaccination prior to sexual activity 3. Screening and treatment of anal HSIL 4. HPV vaccination of sexually active adults Slide 12 of 39 Anal HSIL in HIV-infected women Anal Histology Anal Cytology n (%) of Total N=255 n (%) of HSIL N=72 Normal 101 (40%) 16 (22%) ASCUS/LSIL 129 (50%) 38 (53%) ASC-H/HSIL 25 (10%) 18 (25%) Slide 13 of 39 Note: 8 were unevaluable for anal cytology, including 3 with HSIL Prevalent histologic anal HSIL: 28% Stier E, HPV 2017, CT02

5 AMC-076: Randomized, clinical trial of infrared coagulation of anal HSIL IRC Control P-value* Overall CR Rate 63% (38/60) 27% (16/60) < % CI, 50-75% 95% CI, 16-40% Overall CR/PR Rate 75% (45/60) 95% CI, 62-85% 43% (26/60) 95% CI, 31-57% <0.001 PR rate for those not achieving CR 32% (7/22) 95% CI, 14-55% 23% (10/44) 95% CI, 11-38% * One-sided stratified Mantel-Haenszel chi-square test. Strata were Laser Surgery Center (n=71) and remaining 5 sites (n=49). Slide 14 of 39 Goldstone S, HPV 2017, CT02 Controversies in anal cancer screening Most people with anal HSIL will never develop cancer. Treatment for anal HSIL is not well studied and are clearly less effective than those for cervical HSIL Recurrent HSIL is the norm; multiple treatments are usually needed to clear HSIL Accessing high resolution anoscopy and treatment for anal HSIL is difficult Not yet recommended by organizations setting standards for health care maintenance Cost effectiveness is unclear; Age for screening (35 yrs old?) No consensus on whether to include all women and men with HIV No data that treating anal HSIL will reduce the risk of anal cancer Slide 15 of 39 Oropharyngeal Cancer

Which of these statements is false? 1. The HPV type responsible for most HPV-related oropharyngeal cancers (OPC) is HPV 16 2. Men are more likely than women to develop OPC 3.

HPV related OPC can be prevented in most people through active screening Slide 17 of 39 Oropharyngeal Cancer (OPC) 85% HPV 16 70% HPVrelated 94% of HPVrelated OPC are caused

6 Which of these statements is false? 1. The HPV type responsible for most HPV-related oropharyngeal cancers (OPC) is HPV Men are more likely than women to develop OPC 3. HIV-infected populations are more likely to develop OPC cancer than HIV-uninfected populations 4. HPV related OPC can be prevented in most people through active screening Slide 17 of 39 Oropharyngeal Cancer (OPC) 85% HPV 16 70% HPVrelated 94% of HPVrelated OPC are caused by HR-HPV in 9- valent HPV vaccine Slide 18 of 39 Saraiya M et al JNCI 2015 HPV-Related OPC Incidence is Higher in Men HPV-associated OPC is 2-3 times higher among people 4-fold living with HIV Slide 19 of 39 Jemal, et al. J Natl Cancer Inst 2013

Observed and Projected Incidence Rates for Oropharyngeal Cancers and Cervical Cancer Rates per 100,000 100 10 1 Cervix Oropharynx (overall) Oropharynx (men) Oropharynx (women) There are no accepted

7 Observed and Projected Incidence Rates for Oropharyngeal Cancers and Cervical Cancer Rates per 100, Cervix Oropharynx (overall) Oropharynx (men) Oropharynx (women) There are no accepted 2010screening or prevention modalities for prevention of HPV-related OPC United States Calendar Years Slide 20 of 39 Chaturvedi AK et al. J Clin Oncol. 2011;29: How can we reduce HPVrelated cancers in people living with HIV ANCHOR TRIAL Screen > 17,385 Enroll 5,058 Retain for 5-8 years Estimated < 50 develop cancer Slide 22 of 39 anchorstudy.org; NCT ; Sponsor: NCI

8 Slide 23 of 39 anchorstudy.org; NCT ; Sponsor: NCI Prevention of Anal Cancer with HPV vaccination Excludes those baseline vaccine infection Includes those baseline vaccine infection Slide 24 of 39 Palefsky, NEJM 2011 HPV vaccination: ACTG A5298 Study Design HIV+ 27 yrs No HPV cancers All CD4/RNA RAI for men HRA with bx Anal cyto Anal HPV x 2 Oral HPV x 2 RANDOMIZE: stratify by HSIL, sex, site 4vHPV or placebo: 0, 8, 24 Anal HPV oral HPV Cyto:q6 mo HSIL tx by local standard; HRA providers certified Slide 25 of 39

ACTG A5298: HPV vaccine in HIV+ >27 yrs Outcome 4vHPV (n) Placebo (n) HR (95% CI) Persistent anal HPV, or single detection at last visit 26 33 0.75 (0.45, 1.26) Persistent anal HPV 13 17 0.73 (0.

9 ACTG A5298: HPV vaccine in HIV+ >27 yrs Outcome 4vHPV (n) Placebo (n) HR (95% CI) Persistent anal HPV, or single detection at last visit (0.45, 1.26) Persistent anal HPV (0.36, 1.52) Anal HSIL ( ) Persistent oral HPV (0.02, 0.98) Slide 26 of 39 Wilkin T, CROI 2016 HPV16/18 VE at Non-Cervical Sites Costa Rica Vaccine Trial One-time detection of HPV16/18 infection 4 yrs. after vaccination Slide 27 of 39 1 Herrero R et al. PLOS ONE 2013; 2 Kreimer AR et al Lancet Oncology 2011 Slide courtesy of A Kreimer Strong Association Between Serum and Oral HPV Antibodies Among Vaccinated Men Slide 28 of 39 Pinto et al JID 2016

Prevalence of oral HPV by vaccine status: NHANES 2011-2014 Slide 29 of 39 VLP Vaccines GSK Human Papilomavirus Bivalent (Type 16 and 18) Vaccine, Recombinant HPV 16 and 18 Insect cells Aluminum and

10 Prevalence of oral HPV by vaccine status: NHANES Slide 29 of 39 VLP Vaccines GSK Human Papilomavirus Bivalent (Type 16 and 18) Vaccine, Recombinant HPV 16 and 18 Insect cells Aluminum and TLR 4 agonist adjuvant im injection at 0, 1, 6 months Merck Human Papillomavirus Quadrivalent (Types 6, 11, 16, 18) Vaccine, Recombinant HPV 6, 11, 16, 18 Yeast Aluminum adjuvant im injection at 0, 2, 6 months Human Papillomavirus 9-valent Vaccine, Recombinant adds 31, 33, 45, 52, 59 Slide 30 of 39 These 9 types cause 90% of HPV-related cancers!!! ACIP HPV vaccine recommendations Females Routine vaccination of girls Catch-up vaccination up to age 26 Males Routine vaccination of boys Catch up vaccination up to age 21 Routine vaccination of HIV+ males, other immunosuppressed males, men who have sex with men through age 26 Dosing schedule Two doses (0 and 6 months) when starting prior to age 15 Three doses (0, 1-2, 6 months) after age 15 and if having any immune suppression. Slide 31 of 39 Meites E et al, MMWR, 2016

Real world evidence of HPV vaccine efficacy

infectionrelated cancer by 76% (95% CI 36%-89%)

11 Real world evidence of HPV vaccine efficacy Decline in Genital Warts <30 years of age Slide 32 of 39 START study: Hazard ratio for infection-related cancer Immediate ART reduced infectionrelated cancer by 76% (95% CI 36%-89%) Slide 33 of 39 Borges A, CID 2016 Early ART reducing Anal Cancer Slide 34 of 39

Statin exposure and risk of cancer Death rate 45% lower with statin use Virus-related cancers Statin use associated with significant protection against HPV cancers Slide 35 of 39 Summary Anal cancer

areas o Further study is needed HPV vaccination is the best hope for prevention of noncervical disease in HIV-infected populations o Emerging data support efficacy of vaccination against HPV-related

12 Statin exposure and risk of cancer Death rate 45% lower with statin use Virus-related cancers Statin use associated with significant protection against HPV cancers Slide 35 of 39 Summary Anal cancer is a common cancer in HIV-infected populations Screening for anal cancer should be considered for HIVinfected populations o Data to support this are limited o Existing data is from resource-rich areas o Further study is needed HPV vaccination is the best hope for prevention of noncervical disease in HIV-infected populations o Emerging data support efficacy of vaccination against HPV-related oropharyngeal cancer o Need for efficacy trial to definitively prove efficacy? World-wide push for early initiation of ART (e.g. WHO ) should lead to reduced incidence of HPV-related cancer Slide 36 of 39 Acknowledgments AIDS Malignancy Consortium Joel Palefsky Elizabeth Stier Stephen Goldstone Elizabeth Chiao National Cancer Institute Ligia Pinto Moffitt Cancer Center Anna Giuliano Slide 37 of 39 AIDS Clinical Trials Group Ross Cranston Barbara Bastow Jennifer Webster-Cyriaque Weill Cornell Medicine Christina Megill Marshall Glesby Roy Gulick Funders National Cancer Institute National Institute of Allergy and Infectious Diseases National Institute of Dental and Craniofacial Research

13 Post test question Which of the following groups are not recommended for HPV vaccination according to ACIP? 1. HIV-infected girls age HIV-infected boys age MSM up to age 26 if not previously vaccinated 4. HIV-infected women age with negative hrhpv tests Slide 38 of 39 Question-and-Answer

ACTHIV 2018: A State-of-the-Science Conference for Frontline Health Professionals

ACTHIV 2018: A State-of-the-Science Conference for Frontline Health Professionals ACTHIV 2018: A State-of-the-Science Conference for Frontline Health Professionals Cancer screenings for the HPV Clinician: