The current place of HIV and immunosuppression in lower genital tract pathology- What should the clinician know?

1. The current place of HIV and immunosuppression in lower genital tract pathology- What should the clinician know? Heather Evans October 2005

2. HIV Iatrogenic Immunosuppression

3. HIV/AIDS Development of the epidemic 1981 - First recognised case in America 1983 - Discovery of the virus First case of AIDS in the UK 1984 - Development of the Antibody test 1986 - Zidovudine – first antiretroviral drug 1995 - Development of viral load testing (PCR)

4. Global summary of the HIV/AIDS epidemic, December 2004 • Number of people living with HIV/AIDS Total 39.4 millionAdults 37.2 millionWomen 17.6 million Children under 15 years 2.2 million • People newly infected with HIV in 2004 Total 4.9 millionAdults 4.3 millionWomen 2 million( 2002) Children under 15 years 640 000 • AIDS deaths in 2004 Total 3.1 millionAdults 2.6 millionWomen 1.2 million (2002) Children under 15 years 510 000 Data source: UNAIDS

6. HIV and CIN

7. Scale of the epidemic in UK • More Heterosexual transmission • 12% adult AIDS in women • 70% from heterosexual intercourse • Men & women from or spent time in Sub-Sahara Africa • 53,000 adults by end of 2003, 27% unaware • X2 increase in women infected from 14% in 1990 to 35% in 2000

8. Rates of diagnosed HIV-infected adults seen for care in the UK in1998 and 2003 by residence Data source: SOPHID and CD4 monitoring scheme for Scotland.

9. HIV & AIDS diagnoses and deaths in HIV-Infected individuals by year of occurrence in the United Kingdom, 1993-2002 . Data source: HIV/AIDS reports.

10. HIV in London • 850 HIV positive women gave birth in UK in 2003. • 60% in inner London • Prevalence of 1 in 400 • Elsewhere prevalence 1 in 4,500

11. Target CD4 lymphocytes which produce new viral particles but loose their role in the immune response. Human Immunodeficiency Virus • HIV is a retrovirus that uses its RNA and the host’s DNA to make viral DNA by encoding the enzyme reverse transcriptase allowing DNA to be transcribed from RNA

12. HIV electron micrograph

13. ANTIRETROVIRAL AGENTS FOR HIV

14. HIV: Disease Progression Infection with HIV results in a gradual depletion of CD4 cells Case definition of AIDS: CD4 < 200/μL Opportunistic infection Cancer

15. Immunopathogenesis Systemic immunosuppression • Reduced CD4 counts • High viral HIV load Local immunosuppression • Reduced Langerhans’ cells (Barton 1990) • Impaired CD8 function (Olaitan AIDS 1996)

16. HPV and CIN

19. Association between HIV & CIN • Up to 10% of colposcopy patients HIV+ USA • Prevalence of CIN increased x4-10 • >40% of HIV+ at RFH had abnormal smear at presentation

20. HIV & CIN - Summary • HIV alters the natural history of CIN resulting in rapid progression, a lower rate of regression and an increased recurrence rate following treatment • Increased risk of CIN with advancing immunosuppression • Persistent infection with oncogenic HPV and high HPV load • HIV+ve women often suffer from multifocal disease involving the whole anogenital tract

22. CIN and HAART • HAART improves immunological and virological status allowing clearance of virus • Heard et al AIDS. 2002 CIN regression occurred in 67 (39.9%) of the enrolled women. • Other studies disagree

23. NHS CSP Standards & Quality in Colposcopy Guidelines 2004 • Women newly diagnosed with HIV • Base-line cytology & colposcopy • Annual cytology • Same age range

24. Assessment of HIV women with CIN • Careful colposcopy • Inspect vagina & vulva as higher incidence of multi-focal disease • Biopsy ALL abnormal areas

25. Cervical Screening protocol for HIV-positive women at Royal Free Hospital 3 consecutive negative smears required at 6- monthly interval before back to annual smears

26. HIV and CIN Case Report - Patient X 30 year old Ugandan, married, non-smoker 1995 Moderate dyskaryosis on smear, biopsy CIN3, Laser ablation to 8mm 1996 Severe dyskaryosis on f/u smear 1996/97 2X LLETZ, clear margins 1998 Knife cone biopsy - CIN3 to margins 1999 HIV test - positive

27. HIV & Cervical Cancer

28. HIV and Cervical Cancer • X5 more frequent in HIV positive . • 1993 Cx cancer AIDS defining condition • Commonest AIDS defining malignancy • Unlike Kaposi sarcoma and other AIDS defining neoplasms its occurrence is not dependant on immunocomporomise (Clarke B Mol Pathol 2002)

29. HIV& Cervical Cancer • Poor prognosis • Poor response to therapy • Higher recurrence rates • Higher death rates Maiman et al, 1993, Cancer

30. Immunosuppression and CIN (1) • Women with Renal Failure requiring dialysis Cytology at or shortly after diagnosis Colposcopy if resources permit Any abnormality should be referred to colposcopy • Women about to undergo renal transplant should have had cytology within the past year

31. Immunosuppression and CIN (2) • No indication for increased surveillance for: Cytotoxic chemotherapy Long term steroids Tamoxifem

32. Immunosuppression and CIN (3) Women on cytotoxic drugs for rheumatoid conditions or immunosuppression post transplant • Follow national guidelines • Refer if smear abnormal

33. CONCLUSION • HIV increases risk of CIN because of local & systemic immune impairment • Colposcopists should consider HIV in women with difficult to manage CIN • HIV positive women are 5 times more likely to develop CIN and cervical cancer • New guidelines should improve surveillance & management. • Liaison with HIV physician is an important part of management of infected women