1. HIV AND THE ANUS M62 Coloproctology Course April 2005 Mr P Mullerat, FRCS Prof M C Winslet, MS, FRCS Royal Free and University College Medical School London

2. HIV – AIDS Epidemiology Common anal pathology Chlamydia HPV Herpes

3. HIV epidemiology 42 million people are HIV + worldwide 65000 HIV + in UK

4. HIV epidemiology 42 million people are HIV + worldwide 65000 HIV + in UK 7000 new cases/year 57% acquired by MSM practices Highest incidence in SE England

5. ANORECTAL PATHOLOGY 5% of HIV/AIDS patients are referred to the proctologist

6. ANORECTAL PATHOLOGY 5% of HIV/AIDS patients are referred to the proctologist Common symptoms: Pain (55%) Mass (20%) Bleeding (15%)

7. ANORECTAL PATHOLOGY 5% of HIV/AIDS patients are referred to the proctologist Common symptoms: Pain (55%) Mass (20%) Bleeding (15%) 1/3 will require surgical intervention

8. INITIAL MANAGEMENT Multidisciplinary approach. GUM and AIDS specialists

9. INITIAL MANAGEMENT Multidisciplinary approach. GUM and AIDS specialists Understand homosexual intercourse

10. INITIAL MANAGEMENT Multidisciplinary approach. GUM and AIDS specialists Understand homosexual intercourse Reinforce safe sex

11. INITIAL MANAGEMENT Multidisciplinary approach. GUM and AIDS specialists Understand homosexual intercourse Reinforce safe sex High resolution anoscopy Gonorrhoea and Chlamydia screening HSV, Syphilis, HPV screening if ulcers or fissures

12. COMMON PATHOLOGY HIV related Condylomata49% Anal ulcers 35% Herpes lesions 3% Non HIV related Abscess-Fistula 35% Fissure 32% Haemorrhoids 6%

13. ANAL HERPES Aetiology –HSV – 1 (10%) –HSV – 2 (90%) Symptoms –Irritation –Vesicles –Ulcers –Intense pain Treatment –Acyclovir –Vidarabine

14. ANORECTAL CHLAMYDIA Symptoms –Tenesmus, proctitis, discharge –Anal ulcers –Lymphogranuloma venereum (LGV) Inguinal lymph nodes with erythema Treatment: Tetracycline

15. HUMAN PAPILLOMAVIRUS Epidemiology Natural history Host’s response Management and screening

16. EPIDEMIOLOGY High risk populations Homosexuals Females with Hx of CIN/cervical SCC Partners of above Post-transplant HIV +

17. HPV EPIDEMIOLOGY Incidence of anogenital condylomata in UK Incidence of anal SCC in San Francisco Communicable Disease Report, Vol 9, 44. 1999 J. Palefsky et al, J Infect Dis, 183, 3. 2001

18. NATURAL PROGRESSION Warts 10% AIN I 10% AIN II 10% AIN III 5- 10% Similar behaviour as CIN Anal SCC

19. CONDYLOMATA ? AIN ? SCC

20. ROYAL FREE STUDY Relationship between Local immune response Oncogenic HPV exposure and progression to AIN and SCC?

21. METHODS HPV EXPRESSION HPV DNA typing using SPF and LiPA PCR IMMUNE RESPONSE Density of stromal and epithelial lymphocitic infiltration, using CD3, CD4 and CD8 antibodies Retrospective study (1989 -2001) 82 patients (42 HIV – and 40 HIV +) Paraffin sections

22. Patients HIV – –Warts 12 –LG-AIN 2 –HG-AIN 10 –Anal SCC12 –Controls 6 HIV + –Warts10 –LG-AIN11 –HG-AIN13 –Anal SCC 0 –Controls 6

23. LYMPHOCYTIC INFILTRATE CD4+ expression CD8+ expression HG AIN in HIV + (x250)

24. RESULTS

25. HPV EXPRESSION p>0.05

26. LOCAL IMMUNE RESPONSE * p<0.05

27. Conclusion Factors of disease progression in HIV+ is the poor local immune response. Oncogenic HPV are expressed in 100% of HG-AIN and anal SCC. No difference between HIV + and HIV - groups

28. Management of anal HPV Early detection – Risk populations Accurate staging High resolution anoscopy Cytology – liquid based HPV PCR Markers of progression local CD4-CD8