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The current place of HIV and immunosuppression in lower genital tract pathology- What should the clinician know? Heather Evans October 2005
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)
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
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
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.
HIV & AIDS diagnoses and deaths in HIV-Infected individuals by year of occurrence in the United Kingdom, 1993-2002 . Data source: HIV/AIDS reports.
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
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
HIV: Disease Progression Infection with HIV results in a gradual depletion of CD4 cells Case definition of AIDS: CD4 < 200/μL Opportunistic infection Cancer
Immunopathogenesis Systemic immunosuppression • Reduced CD4 counts • High viral HIV load Local immunosuppression • Reduced Langerhans’ cells (Barton 1990) • Impaired CD8 function (Olaitan AIDS 1996)
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
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
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
NHS CSP Standards & Quality in Colposcopy Guidelines 2004 • Women newly diagnosed with HIV • Base-line cytology & colposcopy • Annual cytology • Same age range
Assessment of HIV women with CIN • Careful colposcopy • Inspect vagina & vulva as higher incidence of multi-focal disease • Biopsy ALL abnormal areas
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
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
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)
HIV& Cervical Cancer • Poor prognosis • Poor response to therapy • Higher recurrence rates • Higher death rates Maiman et al, 1993, Cancer
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
Immunosuppression and CIN (2) • No indication for increased surveillance for: Cytotoxic chemotherapy Long term steroids Tamoxifem
Immunosuppression and CIN (3) Women on cytotoxic drugs for rheumatoid conditions or immunosuppression post transplant • Follow national guidelines • Refer if smear abnormal
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