An Update from The Study of the Prevention of Anal Cancer

Transcription

1 An Update from The Study of the Prevention of Anal Cancer Associate Professor Dave Templeton RPA Sexual Health, Sydney Local Health District Kirby Institute, UNSW Australia 39 th New Zealand Sexual Health Society Conference Christchurch 7-9 th September 2017

2 Why an observational study of HSIL*? HSIL is highly prevalent 30-50% of HIV positive gay men 1 Progression to cancer less common than in cervix About 1/400 per year in HIV positive gay men 1 About 1/4000 per year in HIV negative gay men 1 Treatment of anal HSIL is not standard of care and treatment is difficult. No proof of effectiveness 2 Recurrence rates approximately 50% at 1 year 3 Grade 3-4 side effects in 20-40% 3 *HSIL (high-grade squamous intra-epithelial lesion) = presumed cancer precursor 1. Machalek et al, Lancet Oncol Macaya et al, Coch Database Syst Rev Richel et al, Lancet Oncol 2013

3 3-year natural history study to inform the development of an anal cancer screening program for gay and bisexual men (GBM) GBM aged 35 years (HIV pos & neg) recruited from communitybased settings in Sydney cytology, HPV testing, high-resolution anoscopy (HRA) and biopsies at each of 5 visits over 3 years 617 participants recruited by August 2015

4 High-resolution anoscopy (HRA)

5 Baseline characteristics Overall n=617 HIV Negative n=397 HIV Positive n=220 Age Mean (SD) 50.0 (9.5) 50.1 (10.2) 49.9 (8.1) Smoking status Current 14.1% 11.1% 19.6% Lifetime no. of male partners % 46.6% 63.4% Lifetime R-CLAI % 8.3% 37.3% Male partners last 6 months % 73.6% 69.5% R-CLAI in the past 6 months % 15.4% 37.7%

6 HIV characteristics HIV positive participant characteristics (n=220) Years HIV positive - mean (SD) 15.3 (9.5) Nadir T cell count < % Result of last T cell count < % Currently on treatment 93.6% Detectable viral load on last test 10.4%

7 High diagnostic reproducibility indicates that SPANC findings should be robust and reproducible

8 Am J Surg Pathol 2016;40: PIM is not HSIL does not require close follow-up &/or Rx ThinPrep: accurate and time-saving in cervical screening high prevalence of cytological abnormalities large proportion of slides needing manual review no productivity benefit, which is one of the big advantages in cervical screening. Diagnostic Cytopathology 2016; 44:384-8

9 High-risk (potentially cancer-causing) HPV at baseline Prevalence of any HPV = 87% Prevalence of any HRHPV = 65%

10 HR-9vHPV prevalence at baseline n Prevalence (%) 95% CI HPV HPV HPV HPV HPV HPV HPV Poynten et al (submitted)

11 HR-9vHPV incidence (neg pos pos) UNPUBLISHED DATA SLIDE REMOVED

12 HR-9vHPV clearance (pos neg neg) UNPUBLISHED DATA SLIDE REMOVED

13 HR-HPV summary UNPUBLISHED DATA SLIDE REMOVED

14 SPANC: Baseline prevalence of HSIL Disease category Overall (N=616) HIV-Negative (n=396) HIV-Positive (N=220) p n % (95% CI) n % (95% CI) n % (95% CI) HSIL ( ) ( ) ( ) <0.001 HSIL-AIN ( ) ( ) ( ) HSIL-AIN ( ) ( ) ( ) <0.001

15 SPANC: Baseline prevalence of HSIL Disease category Overall (N=616) HIV-Negative (n=396) HIV-Positive (N=220) p n % (95% CI) n % (95% CI) n % (95% CI) HSIL ( ) ( ) ( ) <0.001 HSIL-AIN ( ) ( ) ( ) HSIL-AIN ( ) ( ) ( ) <0.001 AIN2 related to recent sexual behaviour, not related to immune deficiency a large proportion likely related to acute infection DA Machalek et al, Papillomavirus Research 2016; 2; 97-

16 SPANC: Baseline prevalence of HSIL Disease category Overall (N=616) HIV-Negative (n=396) HIV-Positive (N=220) p n % (95% CI) n % (95% CI) n % (95% CI) HSIL ( ) ( ) ( ) <0.001 HSIL-AIN ( ) ( ) ( ) HSIL-AIN ( ) ( ) ( ) <0.001 AIN2 related to recent sexual behaviour, not related to immune deficiency a large proportion likely related to acute infection AIN3 related to lifetime behaviours, immune function a large proportion likely related to chronic infection DA Machalek et al, Papillomavirus Research 2016; 2; 97-

17 HSIL over time UNPUBLISHED DATA SLIDE REMOVED

18 Predictors of HSIL clearance (pos neg neg) UNPUBLISHED DATA SLIDE REMOVED

19 HSIL persistence/clearance summary UNPUBLISHED DATA SLIDE REMOVED

20 What about screening tests to detect those at highest risk of anal cancer?

21 Cancer Cytopathology 2016; 124: SPANC (among the best) European Journal of Cancer Prevention 2017 (in press) Initial = 9.9% ; Repeat = 4.7% Less common among those with histologic HSIL & more HSIL More common: less receptive anal sexual experience; douching with soapy water; feeling more nervous during exam Avoiding douching with soapy water and strategies to aid patient relaxation during sampling may reduce the unsat rate

22 Studies Referral (%) Sensitivity (%) Specificity (%) PPV (%) NPV (%) Cytology HRHPV viral load E6/E7 mrna HPV VL or HPV16/18 E6/E7 mrna HRHPV and E6/E7 mrna HRHPV viral load and E6/E7 mrna outperformed anal cytology in detecting anal HSIL Fewer referrals (for further assessment by HRA/Biopsy) Comparable sensitivity and specificity longitudinal studies needed to evaluate long-term performance

23 SPANC finding at 12mth F-U Potential implications UNPUBLISHED DATA SLIDE REMOVED

24 In conclusion. Anal cancer is a huge & ing problem in GBM (esp HIV+) Interim SPANC results show great promise in: better understanding the natural history of anal HSIL identifying a minimally invasive screening program for persistent HSIL (& thus GBM at highest risk of anal ca) UNPUBLISHED DATA REMOVED We need more anoscopists

25 Acknowledgements Kirby Institute, UNSW St Vincent s Hospital, Sydney University of Sydney Andrew Grulich Carmella Law Kirsten McCaffery Mary Poynten Winnie Tong Kirsten Howard Daniel Seeds Jeff Jin Eddie Fraissard Brian Acraman David Ninham Garrett Prestage Douglass Hanly Moir Pathology Andrew Carr Patrick McGrath Annabelle Farnsworth Robert Mellor Jennifer Roberts RPA Sexual Health Piero Pezzopane Adele Richards David Templeton Kathy Petoumenos Julia Thurloe Matthew Law Western Sydney Sexual Health Richard Hillman Rick Varma Julian Langton-Lockton Community representatives Lance Feeney Russ Gluyas Melbourne Sexual Health Centre Kit Fairley Royal Women s Hospital, Melbourne Suzanne Garland Sepehr Tabrizi Alyssa Cornall Samuel Philips Dorothy Machalek The SPANC team thanks the participants. The SPANC study is funded by a NHMRC program grant (# ) and a Cancer Council NSW Strategic Research Partnership Program grant (#13-11). Cytological testing materials are provided by Hologic (Australia) Pty Ltd. The Kirby Institute is affiliated with the Faculty of Medicine, University of New South Wales and funded by the Australian Government of Health and Ageing. The views expressed in this publication do not necessarily represent the position of the Australian Government.