1. www.ias2013.org Kuala Lumpur, Malaysia, 30 June - 3 July 2013 Prevalence of anal Human Papillomavirus (HPV) infection and anal squamous intraepithelial lesions (SIL) in a Cohort of Brazilian HIV-infected women Beatriz Grinsztejn 1, Ruth Khalili Friedman 1, Valdilea Veloso 1, Monica Derrico 1, Cynthia B. Cunha 1, Carina Barillo 1, Brenda Hoagland 1, Sandra Wagner 1, Angela C.V. de Andrade 1, Andrea Cytryn 1, José Eduardo Levi 2, Thais Heinke 3, Janice Mery C. de Oliveira Coelho 1, Paula Mendes Luz 1, Jose Ricardo Coutinho 1 1 Fundação Oswaldo Cruz – Instituto de Pesquisa Clínica Evandro Chagas/IPEC, Rio de Janeiro, State of Rio de Janeiro, Brazil. 2 Laboratório de Virologia - Instituto de Medicina Tropical, Universidade de São Paulo, State of São Paulo, Brazil. 3 Salomão Zoppi Diagnósticos Abstract no. WEPDB0103

2. www.ias2013.org Kuala Lumpur, Malaysia, 30 June - 3 July 2013 Background Anal cancer in specific populations, such as people living with HIV/AIDS, has been increasing at alarming rates. The incidence of anal carcinoma (AC) has been increasing despite the implementation of ART, which has not been shown to consistently alter the course of HPV-associated anogenital disease

3. www.ias2013.org Kuala Lumpur, Malaysia, 30 June - 3 July 2013 Methods Study Design and Population: Cross-sectional study conducted in the IPEC-Fiocruz HIV+ women cohort in active follow-up between January 2011 and December 2012. Women aged ≥18 years without a history of anal cancer were accessed. Data Collection: Structured interviews were performed to access sociodemographic characteristics and risk behaviors; data on HIV-related parameters and medical conditions were captured from the medical charts. All procedures were performed after obtaining IRB approval and written informed consent from study participants.

4. www.ias2013.org Kuala Lumpur, Malaysia, 30 June - 3 July 2013 Methods Anal Liquid-based Cytology: Samples collected in ThinPrep™ solution. Results reported according to Bethesda criteria; HPV Testing using PapilloCheck: HR-HPV: 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68, 26, 53, 66, 70, 73, 82 LR-HPV: 6, 11, 40, 42, 43, 44/55 Anal examination and High Resolution Anoscopy (HRA): Performed for women with an abnormal cytology result and/or visible hypercromic lesions on anal margin. Biopsies were performed as clinically required.

5. www.ias2013.org Kuala Lumpur, Malaysia, 30 June - 3 July 2013 Methods Statistical Analysis: Anal HPV testing results, cytology results and the frequency of histological AIN and anal cancer (margin and/or canal) were calculated as simple proportions. Women who had normal cytology and no visible lesions were considered as negative for AIN. Histological results were considered for the final diagnostic. If multiple biopsies were obtained, the highest grade was used to denote the lesion status at that visit. The STATA/SE 10.1 software package was used in the analysis.

6. www.ias2013.org Kuala Lumpur, Malaysia, 30 June - 3 July 2013 Results Characteristics of participants in the IPEC/FIOCRUZ Women`s Cohort (N=816) CharacteristicsTotal a Age ≥ 40. years - N (%) 497 (60.9) Median (IQR) 41.5 (34.6-48.6) Skin color non white - N (%) 298 (36.9) No. of sexual partners in past 6 months - N (%) 0235 (29) 1531 (65.6) ≥ 243 (5.3) Median (IQR) 1 (0-1) Receptive anal intercourse in past 6 months - N (%)163 (20.3) Current smoker - N (%)172 (21.2)

7. www.ias2013.org Kuala Lumpur, Malaysia, 30 June - 3 July 2013 Results Characteristics of participants in the IPEC/FIOCRUZ Women`s Cohort (N=816) CharacteristicsTotal Nadir CD4+ cell count. cells/mm3 – Median (IQR)219 (103-326) Baseline CD4+ cell count. cells/mm3 – Median (IQR) Combined antiretroviral therapy (cART) 595 (408-837) 629 (77,1%) Time under cART (months) Mean (SD)90.4 (64.0) Median (IQR)77.5 (32.7-149) < 200 45.8%

8. www.ias2013.org Kuala Lumpur, Malaysia, 30 June - 3 July 2013 Results CytologyN (%) No lesions571 (70) ASC-US111 (13.6) ASC-H11 (1.3) LSIL88 (10.8) HSIL35 (4.3) Total816 (100) Anal cytology was abnormal in 245/816 (30%) women: Of these, 204 (83.3%) were submitted to HRA.

9. www.ias2013.org Kuala Lumpur, Malaysia, 30 June - 3 July 2013 Results Prevalence of anal histological HPV-related lesions. HPV-related lesions N (%) Total a (n = 775) AIN 1 41 (5.3) 21 (2.7) 34 (4.4) 55 (7.0) AIN 2 AIN 3 AIN2+ a 41 women were not considered as they presented abnormal cytology results and did not come to HRA. Among all women with histological AIN2+, 7.3%, 70.9% and 21,8% had lesions only in the anal margin, only in the anal canal and in both sites, respectively.

10. www.ias2013.org Kuala Lumpur, Malaysia, 30 June - 3 July 2013 * Total of women with available HPV genotyping results Prevalence of High risk HPV genotypes in all women (N=717)*

11. www.ias2013.org Kuala Lumpur, Malaysia, 30 June - 3 July 2013 * Total of women with available HPV genotyping results Prevalence of Low Risk HPV genotypes in all women (N=717)*

12. www.ias2013.org Kuala Lumpur, Malaysia, 30 June - 3 July 2013 Conclusions The prevalence of abnormal anal cytology was high. Prevalence of histological AIN2+ may be underestimated as women with normal cytology were not referred to HRA. Systematic screening for HPV-related anal lesions among women is warranted and may impact the increasing incidence of anal cancer, although a screening algorithm is not yet defined. HIV+ women may benefit from the HPV vaccines already available. However, further studies are needed to investigate the role of other HPV types involved in high grade HPV-related lesions among HIV-infected women in developing countries.