Seroprevalence, prevalence, type and factors associated with HPV infection at multiple sites in young HIV-positive MSM On behalf of the HPV MAPS Research Group C Sadlier1,2, S O’Dea1, S Delamere1, P Smyth3, N Myers3, G Blackshields3, F Van Der Klis, O Sheils2,3, C Bergin1,2 Department of GU Medicine and Infectious Diseases (GUIDE), St James’s Hospital, Dublin, Ireland. Department of Clinical Medicine, Trinity College Dublin, Dublin, Ireland. Department of Histopathology, Trinity College Dublin, Dublin, Ireland. National Institute for Public Health and the Environment, Blithoven, Netherlands.

HPV infection HPV is the most common STI worldwide Broad spectrum of clinical presentations: Asymptomatic infection Genital warts Invasive malignancy HPV infection now causes >5% of cancers worldwide So, I think that all of us here are familiar with HPV. It’s the most common STI worldwide with 40 of the known 200 HPV genotypes causing genital infections. HPV infection causes a huge spectrum of clinical presentations including transient asymptomatic infections, genital warts and at the other end of the spectrum – invasive malignancies including cervical cancer, oropharyngeal cancer, anal cancers and penile cancers. And while we have observed a dramatic decrease in the incidence of cervical cancer owing to the implementation of successful screening programmes, we have seen a significant increase in HPV related oropharyngeal cancers and anal cancers during the same period. (1) Jemal et al., 2013 Background l Aims l Methods l Results I Discussion l Conclusion

HPV associated anal cancer GUIDE cohort 2006-2015, 7 cases anal cancer (44/100,000) (1) Characteristics of Anal CA cases N= 7 (%) Median [IQR] age 38 [35-49] Male 6 (86) Heterosexual 1 (14) MSM 4 (57) IDU 2 (29) Median [IQR] CD4 count (cells/mm3) 239 [135-401] Median [IQR] Nadir CD 4 count (cells/mm3) 18 [6-19] On HAART Smoker So, I think that all of us here are familiar with HPV. It’s the most common STI worldwide with 40 of the known 200 HPV genotypes causing genital infections. HPV infection causes a huge spectrum of clinical presentations including transient asymptomatic infections, genital warts and at the other end of the spectrum – invasive malignancies including cervical cancer, oropharyngeal cancer, anal cancers and penile cancers. And while we have observed a dramatic decrease in the incidence of cervical cancer owing to the implementation of successful screening programmes, we have seen a significant increase in HPV related oropharyngeal cancers and anal cancers during the same period. (2) Sadlier et al., Under review STD 2016. Background l Aims l Methods l Results I Discussion l Conclusion

Prevention of HPV associated disease HPV vaccine has potential to greatly impact the burden of HPV associated disease BHIVA HPV vaccine recommendations for HIV-positive adults (3) Documenting baseline epidemiology of HPV infection in young HIV+ MSM is important in guiding primary and secondary prevention strategies (3) Geretti et al., 2016. Background l Aims l Methods l Results I Discussion l Conclusion

Objectives Investigate prevalence of hr HPV at multiple sites in young HIV+ MSM The aims of this project were to.... Background l Aims l Methods l Results l Discussion l Conclusion

Objectives Investigate prevalence of hr HPV at multiple sites in young HIV+ MSM Investigate prevalence of anti-HPV 16/18 antibodies The aims of this project were to.... Background l Aims l Methods l Results l Discussion l Conclusion

Objectives Investigate prevalence of hr HPV at multiple sites in young HIV+ MSM Investigate prevalence of anti-HPV 16/18 antibodies Investigate factors associated with hr HPV infection The aims of this project were to.... Age , CD4, HAART, HIV VL Background l Aims l Methods l Results l Discussion l Conclusion

Objectives Investigate prevalence of hr HPV at multiple sites in young HIV+ MSM Investigate prevalence of anti-HPV 16/18 antibodies Investigate factors associated with hr HPV infection Estimate susceptibility to HPV types covered by HPV-4v and HPV-9v The aims of this project were to.... Age , CD4, HAART, HIV VL Background l Aims l Methods l Results l Discussion l Conclusion

Methods Study Design HIV+ MSM >18 and < 26 years (n=50) Enrolment from a single site, the GUIDE clinic, St James’s Hospital, Dublin Data Collection Oropharyngeal, anal and penile swabs Serum for anti-HPV 16/18 antibodies Demographic and Sexual behaviour data collected Ethics approval from St James’s Hospital REC Pilot Single site Background l Aims l Methods l Results l Discussion l Conclusion

Methods Sample analysis Swabs analysed for HPV DNA by Multiplex PCR using PGMY09/11 consensus primers HPV DNA processed using Next Generation Sequencing(4) Raw data mapped against all known HPV genotypes(5) HPV Classification hr HPV types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59 Quadrivalent vaccine (HPV 4v) 6, 11, 16, 18 Nonavalent vaccine (HPV 9v) 6, 11, 16, 18, 31, 33, 45, 52, 58 Serum HPV 16/18 antibodies were measured against the L1 portion of the VLP using a multiplex immunoassay PAPILLOMA VIRUS GENOME DATABASE Raw data mapped against all known HPV genotypes which measured HPV specific antibodies against L1 VLP of genotypes 16 and 18 and are reported in LIU/ml ((4)ion Torrent Platform®, (5)http://pave.niaid.nih.gov/#home) Background l Aims l Methods l Results l Discussion l Conclusion

Results Selected baseline characteristics N=50 (%) Median Age [IQR] 25 [23-26] Current smoker, N (%) 20 (40) Duration of HIV infection (years) 2 [1-3] CD4+ T count cells/mm3 580 [440-696] On HAART N (%) 43 (86) Viral load not detected N (%) 36 (72) Data reported as median [interquartile range, IQR] unless otherwise stated Abbreviations: HAART highly active antiretroviral therapy, N number Background l Aims l Methods l Results l Discussion l Conclusion

Results Selected baseline characteristics N=50 (%) Age at sexual debut (years) 16.5 [15-17.3] Lifetime number sexual partners 10 [3-20] Number of sexual partners past 3/12 1 [0-1.5] Data reported as median [interquartile range, IQR] unless otherwise stated Background l Aims l Methods l Results l Discussion l Conclusion

Detected Not-detected HPV DNA Detected Not-detected N=34 (68%) N=16 (32%) Of the 50 patients that were screened, 8 tested positive... Background l Aims l Methods l Results l Discussion l Conclusion

Detected Not-detected HPV DNA Detected Not-detected N=34 (68%) N=16 (32%) Concurrent HPV infection ? % Background l Aims l Methods l Results l Discussion l Conclusion

hr HPV genotypes 54% hr HPV detected on anal swabs 6% hr HPV detected on penile swabs Hr HPV not detected on oropharyngeal swabs Number with hr HPV detected Hr HPV type Background l Aims l Methods l Results l Discussion l Conclusion

Anti-HPV 16 antibodies Detected N=22 (44%) Of the 50 patients that were screened, 8 tested positive... Background l Aims l Methods l Results l Discussion l Conclusion

HPV antibodies Anti-HPV 16 antibodies Detected N=22 (44%) Of the 50 patients that were screened, 8 tested positive... Background l Aims l Methods l Results l Discussion l Conclusion

HPV antibodies Anti-HPV 16 antibodies Detected N=22 (44%) 16% both HPV 16 and 18 antibodies detected (N=8) Anti-HPV 18 antibodies Detected N=13 (26%) Of the 50 patients that were screened, 8 tested positive... Background l Aims l Methods l Results l Discussion l Conclusion

Concordance of HPV detection Anti-HPV 16 antibodies Detected N=22 (44%) 9/22 with Anti-HPV 16 antibodies Detected had HPV16 on swabs Anti-HPV 18 antibodies Detected N=13 (26%) 2/13 with Anti-HPV 18 antibodies Detected had HPV18 on swabs Background l Aims l Methods l Results l Discussion l Conclusion

HPV vaccine genotypes HPV 4v vaccine types HPV 9v vaccine types % with vaccine type HPV detected HPV type detected HPV type not-detected Background l Aims l Methods l Results l Discussion l Conclusion

HPV vaccine immunogenicity study 47 of 50 (94%) recruited to the HPV prevalence study completed the HPV vaccine course 100% seronegative for HPV 16 and 86% seronegative for HPV 18 seroconverted post completion of HPV vaccine course Of the 50 patients that were screened, 8 tested positive... Background l Aims l Methods l Results l Discussion l Conclusion

Limitations Small sample size Study group were relatively homogenous Relatively high CD4/nadir CD4 Virally suppressed on HAART High risk sexual behaviour Point prevalence study We examined anti-HPV 16/18 antibodies only Background l Aims l Methods l Results I Discussion l Conclusion

Conclusion A significant proportion of young HIV+ MSM are infected with one or more hr HPV type The majority could derive some benefit from HPV vaccine Frequent non-vaccine hr HPV types were observed Requirement for improved primary and secondary prevention interventions in HIV+ MSM (51, 56, 59) The high prevalence of hr HPV infection, in combination with a rising anal cancer incidence, highlights the Background l Aims l Methods l Results l Discussion l Conclusion

Acknowledgements Patients who participated in the study HPV MAPS research group S O’Dea S Delamere F Van Der Klis P Smyth O Sheils C Bergin Dr F Van Der Klis Staff in the GUIDE clinic Background l Aims l Methods l Results l Discussion l Conclusion