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

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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

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HIV Iatrogenic Immunosuppression

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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)

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

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

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Human Immunodeficiency Virus

• HIV is a retrovirus that uses its RNA and the
  hosts DNA to make viral DNA by encoding the
  enzyme reverse transcriptase allowing DNA to be
  transcribed from RNA

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HIV electron micrograph
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ANTIRETROVIRAL AGENTS FOR HIV
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HIV Disease Progression
Infection with HIV results in a gradual depletion
of CD4 cells Case definition of AIDS CD4 lt
200/µL Opportunistic infection Cancer
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Immunopathogenesis

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

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HPV and CIN
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Association between HIV CIN

• Up to 10 of colposcopy patients HIV USA
• Prevalence of CIN increased x4-10
• gt40 of HIV at RFH had abnormal smear at
  presentation

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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
• HIVve women often suffer from multifocal disease
  involving the whole anogenital tract

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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

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NHS CSP Standards Quality in Colposcopy
Guidelines 2004

• Women newly diagnosed with HIV
• Base-line cytology colposcopy
• Annual cytology
• Same age range

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Assessment of HIV women with CIN

• Careful colposcopy
• Inspect vagina vulva as higher incidence of
  multi-focal disease
• Biopsy ALL abnormal areas

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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
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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

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HIV Cervical Cancer
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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)

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HIV Cervical Cancer

• Poor prognosis
• Poor response to therapy
• Higher recurrence rates
• Higher death rates
• Maiman et al, 1993, Cancer

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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

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Immunosuppression and CIN (2)

• No indication for increased surveillance for
• Cytotoxic chemotherapy
• Long term steroids
• Tamoxifem

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Immunosuppression and CIN (3)

• Women on cytotoxic drugs for rheumatoid
  conditions or immunosuppression post transplant
• Follow national guidelines
• Refer if smear abnormal

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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