1. #AIDS2016 | @AIDS_conference Cervical Cancer Prevention in Africa: The Future Nelly Yatich, DrPH University of California San Francisco July 19 th, 2016

2. #AIDS2016 | @AIDS_conference DISCLOSURE I have no financial or other conflicts of interest to declare

3. #AIDS2016 | @AIDS_conference Magnitude of cervical cancer Globally 528,000 cases diagnosed per year ~ 85% of global burden in the developing world Accounts for ~ 12% of all female cancers in the developing world High ASRs >30 per 100,000, include E. Africa (42.7), Melanesia (33.3), Southern (31.5) and Middle (30.6) Africa Remains the most common cancer in women in Eastern and Middle Africa Globally 266,000 deaths per year Accounts for 7.5% of all female cancer deaths Almost 87% cervical cancer deaths occur in developing countries Rates of > 20 per 100,000 in in Melanesia (20.6), Middle (22.2) and Eastern (27.6) Africa Globocan, 2012

4. #AIDS2016 | @AIDS_conference Cervical cancer burden in HIV/AIDS HIV Prevalence 2014 (UNAIDS) Cervical cancer incidence (Globocan, 2012)

5. #AIDS2016 | @AIDS_conference Cervical cancer in women with HIV Increased longevity of patients on ART may: – Increase risk of exposure to HPV – Provide the time required for progression to cervical cancer HIV-positive women are more likely to have: – Human Papilloma Virus (HPV) infection – Persistent infection with high risk HPV – An increased risk of developing precancerous lesions – A recurrence of precancerous lesions after treatment – Precancerous lesions that progress rapidly to cervical cancer – Higher risk of developing cervical cancer than HIV(-) women

6. #AIDS2016 | @AIDS_conference Model of HPV–related CIN and cervical cancer with ART Palefsky, Current Opinion in Oncology, 2003

7. #AIDS2016 | @AIDS_conference Screening for cervical cancer Cytological screening of women has resulted in a decline in cervical cancer deaths in wealthier countries High mortality in the developing world due to shortage of high- quality precancer screening and treatment programs Most developing countries lack infrastructure and trained personnel for cytology VIA has been reported to have sensitivity values comparable to Pap and provides opportunity to “see and treat” VIA Accuracy: – Depends on provider experience – May miss small or endocervical lesions – Requires pelvic exam (space, supplies, fear by clients)

8. #AIDS2016 | @AIDS_conference The future – HPV screening Precision oncology: Interventions concentrated on those who will benefit, sparing expense and side effects for those who will not HPV testing is: – Etiology-based – Has been shown to be more sensitive, with higher positive and negative predictive value than cytology – Is more readily exportable to low resource settings 2013 WHO guidelines recommend: – HPV over VIA, where possible – Treatment based on screening results alone – Cryotherapy as standard treatment, LEEP at referral centers

9. #AIDS2016 | @AIDS_conference Cluster RCT of 52 villages in India (131,746 women) Random assignment to – HPV testing – Cytology – VIA – Standard Care Outcome: Cervical cancer incidence or death

10. #AIDS2016 | @AIDS_conference India Trial, Results Test positivity rates: – HPV: 10%, Cytology 7%, VIA 14% Detection rate for CIN1 was higher in the VIA group Detection rate for CIN 2 and 3 similar across all three groups

11. #AIDS2016 | @AIDS_conference

13. The future – HPV Vaccination Gardasil ® (Merck) and Cervarix ®(GSK) Efficacy 96-98% in prevention of cervical pre-cancers Both vaccines appear to offer cross-protection against other HPV types Vaccine most effective if given before 1st sexual contact Administered as a series of 3 injections over a 6-month period at 0, 1-2, and 6 months Challenges for developing countries: Health care infrastructure Capacity for initiating and sustaining an immunization program for adolescents Affordability and cost-effectiveness of vaccination relative to other programs competing for resources Cultural acceptability Political will

14. #AIDS2016 | @AIDS_conference Research Priorities Optimal screening strategies for cervical cancer precursors in Africa – Role of HPV testing – Role of self-collection – Testing at community settings – Point of care treatment Integration of HPV vaccine with screening in developing countries Second generation of prophylactic HPV vaccines

15. #AIDS2016 | @AIDS_conference How can evidence-based strategies be successfully implemented? Systematic assessment of the barriers and facilitators to implementation of the interventions Partnership with the communities and stakeholders to develop feasible and sustainable strategies Ensure that strategies as implemented remain faithful to original intervention Cost effectiveness analysis

16. #AIDS2016 | @AIDS_conference Community-based HPV testing Outreach and education: – Use a brief educational module validated in this setting for use by CHWs – Provide outreach, education and screening in most accessible location Screening: – Low-cost HPV screening available – Self-collected specimens eliminate many barriers to VIA/screening Notification of results: – Text message, phone call results with follow-up information Treatment: – Cryotherapy, with LEEP for larger lesions – Linkage strategies to be developed with communities

17. #AIDS2016 | @AIDS_conference Conclusion Cervical cancer remains a huge burden of disease for women in resource-limited settings HIV infection is associated with higher incidence of cervical cancer and CIN/SIL Alternatives to cytology, such as HPV testing, are critical to ensure adequate coverage and appropriate interventions Community partnership is key Although current vaccines are highly effective in women, implementation of HPV vaccination in developing countries remains a challenge