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Cervical Cancer and AIDS -related malignancies Dr Masangu Mulongo IAS Conference, Durban 2016

Cervical Cancer and AIDS -related malignancies Dr Masangu Mulongo IAS Conference, Durban 2016. AIDS-related malignancies. People living with HIV/AIDS have a higher risk of developing the following cancers : AIDS-defining malignancies: Cervical Cancer(HPV )

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Cervical Cancer and AIDS -related malignancies Dr Masangu Mulongo IAS Conference, Durban 2016

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  1. Cervical Cancer and AIDS -related malignancies Dr Masangu Mulongo IAS Conference, Durban 2016

  2. AIDS-related malignancies People living with HIV/AIDS have a higher risk of developing the following cancers: AIDS-defining malignancies: • Cervical Cancer(HPV) • Kaposi’s Sarcoma (Human Herpes Virus 8) • Non-Hodgkin’s Lymphoma( EBV)(Burkitt’s Lymphoma) Other less common cancers in HIV/AIDS: • Hodgkin’s Lymphoma • Anal & Penile Cancer • Liver Cancer • Lung cancer • Testicular cancer

  3. World Incidence of Common Cancers • Globally, Breast Cancer is the leading female cancer…. • BUT in the developing world Cervical Cancer is the No. 1 cancer killer in women • High co-morbidity of cervical cancer with HIV

  4. Estimated cervical cancer incidence worldwide (2012) GLOBOCAN, 2012

  5. Global Primary Prevention: HPV Vaccination

  6. Global Secondary Prevention:

  7. Coverage of cervical cancer screening in 57 countries (Gakidou, 2008)

  8. Anatomy of the Cervix

  9. Cause: Human Papillomavirus (HPV) Double stranded DNA virus Grouped into low and high risk depending on malignant potential Over 130 different genotypes / 40 types infect genital tract Infects both men and women Transmitted sexually (in most cases) Worldwide types 16/18 most common in ICC, Southern Africa 16/18 only 40% 80% eliminated by immune system within ± 18 months in most cases; 20% persist

  10. Risk Factors for HPV infection • Age of first intercourse/early sexual debut • Number of lifetime partners • Current use of oral birth control • Educational level/Poverty/Diet • Smoking • Family history • HIV OVERRIDES ALL OF THESE TRADITIONAL RISK FACTORS

  11. Natural history of HPV infection I N F E C T I O N Immune Response First Lesion About 9 months Sustained clinical remission Late Stage Active Growth (3–6 months) Incubation (1–8 months) Host Containment (3–6 months) Persistent or recurrent disease

  12. ~40% HPV Infection Low- grade CIN (CIN 1) High- grade CIN (CIN 2/3) Invasive Cancer 60% 20% 20-30% Natural history of cervical cancer in HIV negative patients

  13. 10–15 years? Basement Membrane CIN 1 CIN 2 CIN 3 Cancer Natural history of cervical cancer

  14. CERVICAL CANCER : CLINICAL PROGRESSION Normal HSIL ICC (CIN2/3) IMMUNOCOMPETENT THIS PROCESS CAN TAKE 15 YEARS HIV FASTER

  15. Cervical cancer in HIV + women • The risk of HPV infection – including infection with multiple hrHPV types – is substantially higher in HIV+ women • HIV+ women are at 2-5x higher risk of cervical pre-cancer and cancer • Prolonged life-expectancy on ART means they now live long enough to develop and die from cancer than OIs. • HIV+ women present with cervical cancer at much younger ages • Treatment of cervical cancer is also more complicated in HIV+ women, making cure more difficult to achieve

  16. HIV / AIDS and Cervical Dysplasia Prevalence rates – higher • USA -16.2% Dysplasia (LSIL 14.1%, HSIL 2.1%) • 4% Dysplasia in HIV negative Massad et al AIDS 2004 18: 109-113 • Europe-26.5% Dysplasia ( LSIL 19%, HSIL 7.5%) 7.5% in HIV negative Six etal AIDS 1998 12;(1047-1756) • Brazil 26.7% Dysplasia (LSIL 21% HSIL 5.7%) personal communication Professor Breatriz Grinsztejn • Zambia 76% Dysplasia (HSIL 33% 43% LSIL)Parham et al GynecolOncol 103 (1017-10220 • South Africa 51% Dysplasia (HSIL 18% and 23.5% LSIL) Firnhaber et al Cancer Causes Control epub 1 Dec 2009 HIV unknown status 26% Dysplasia ConjeInt J GynaecolObstet 84:101-108 South Africa --rural areas (unpublished confirmed reports of 60% HSIL)

  17. HIV positive women have higher rates of HPV and significant diversity • Our clinic in Jo’burg (191 women screened) Over 80% our women screened have an HR type of HPV Two women had 8 different oncogenic types Different types also 40% 16 then 56, 66 ZAMBIA- 85% had HR HPV types 52, 58 BRAZIL - 38.6% HR HPV THAILAND- 51% HR HPV Types 16 and 18 seen but also 33,35,52,53 and 81

  18. 100% 80% 60% 40% 20% 0% HPV 16 HPV 18 HPV 33 HPV 56 HPV 59 HPV 66 Any HPV Oncogenic Multiple Prevalence of HPV types by cervical disease among 191 HIV-HPV infected women Normal N=90 AGUS/ASCUS N=14 LSIL N=51 HSIL N=36

  19. Prevalence of HPV types by CD4 category 100% 80% 60% 40% 20% 0% HPV 16 HPV 18 HPV 33 HPV 56 HPV 59 HPV 66 Any HPV Oncogenic Multiple oncogenic <200 200-500 >500

  20. Progression Rates higher • Italian group found cervical dysplasia progressionrates in HIV positive women higher OR 3.506 95% CI (0.816-15.0) • HPV clearance was seen in 69% HIV negative vs. 22.8% in HIV + women OR 0.33 95% CI (0.163-0.670) Branca et rnational J STD & Aids 2003 14 (417-425) • USA group found progression in 20% HIV positive women vs. 5% HIV negative women in 30 months of follow up (incidence of 8.3 and 1.8 cases per 100 years P< .001) EllerbrookJama2000 1031-1037

  21. Regression rates lower • Same Italian group found dysplasia regressed more frequently in HIV negative women, more frequently than HIV positive women: 13.5% vs. 7.9% OR 0.584 95% CI 0.2-1.5) • Another European group found that 69% of LSIL regressed in HIV negative women (and HIV positive women CD>500) vs. 20% regression of LSIL lesions in HIV positive with CD4 <500Six etal AIDS 1998 12;(1047-1756)

  22. Condoms • A study in HIV negative women showed a decrease in the rate of genital HPV infection from 89.3 per 100 patient-years at risk, in women reporting inconsistent partner condom use to 37.8 patient-years at risk, in women reporting 100% partner condom use • Consistent use of condoms increases the clearance of HPV and increases the rate of regression.WinerN Engl J Med.2006;354:2642-2654. • Our study in HIV + women who used condoms had a lower risk of HSILPR=0.7 CI (0.5-0.9) no effect on risk LSIL Firnhaber et al Cancer Causes Control epub 1 Dec 2009

  23. Primary Prevention of Cervical Cancer:HPV Vaccination • Vaccine protects against 70% of CC • Dosage: 0,1ml given at 0, 1 and 6 months • Efficacy of 2 doses: study by Dobson et al ( JAMA) showed • Immunogenicity of 2 doses given to girls 9-13yrs at 0 and 6 • Months was as effective against types 16 & 18 as 3 doses • TYPES: - Bivalent (GSK) : 16, 18 HR HPV types (Cervarix) • - Quadrivalent (Merck) : 6, 11, 16, 18 (Gardasil) • - Nanovalent (6, 11,16,18, 31, 33, 45, 52, 58) (Gardasil 9) • ISSUES -Cost (in RLCs) • - Bivalent : R 500-800/ dose x 3doses • - Quadrivalent : R 900+ /dose x 3 doses • - Safety in HIV & Pregnancy • - Safe in HIV : not live attenuated vaccine • - Safe in pregnancy, but not recommended • ELIGIBILITY: - Girls & Boys, 9-26yrs,

  24. Secondary Prevention of Cervical Cancer: • Screening Modalities: • The Papanicolaou test ( Pap smear or Pap test) • is a routine test used to screen for cervical cancer. • The test looks for abnormal changes in the cells of the cervix that could indicate a precancerous condition or cervical cancer. • Liquid-based cytology (LBC) • VIA/VILI (Visual inspection with acetic acid/ Lugol’s iodine) • “See & Treat” screening involving the application of vinegar/ dye to the cervix and identifying an abnormality • 4 HPV Testing • Molecular testing for DNA of HPV

  25. Secondary prevention: Pap smear screening

  26. Visual Inspection of the Cervix- VIA See and Treat Place 5% acetic acid or Iodine on the cervix White areas consider abnormal Freeze with cryotherapy using N2O or CO2

  27. Guidelines for managing pap smears in HIV (SA HIV 2010)

  28. VIA studies • VIA has been shown to be at least or even more sensitive than the Pap smear but not as specific in several studies in multiple countries ( non HIV) • A study in India reports an 88% sensitivity and a 78%specificity for VIA compared with the gold standard of colposcopy with biopsy. • One study performed in Nicaragua shows that VIA detected up to twice as many invasive cancers but that for every diagnosis, eight false positives were identified at the referral center.

  29. Comparison of Cervical Cancer screening tests 85% 85%

  30. Definitive Diagnosis of Cervical Cancer: Colposcopy &Biopsy • One of the techniques to locate abnormal appearing epithelium place acetic acid on the cervix • Direct biopsies to suspicious areas • Biopsy necessary to establish origin of acetowhite area or abnormal vessels (mosaic, punctuation)

  31. Treatment Of pre-cancerous lesions: Removal abnormal Transformation Zone: • Excisional treatment: • LEEP / LLETZ: Loop electrical excision procedure/ Lagre Loop Electrical Excision of the TZ • under colposcopic guidance, outpatient, specific criteria • Cold knife cone biopsy 2. Ablative treatment: • Cryotherapy: cryo-necrosis with N2O, specific criteria Of cancerous lesions: • Hysterectomy • Chemo-radiation • Palliative care

  32. LEEP/LLETZ Utensils LEEP /LLETZ Machine

  33. LEEP/LLETZ PROCEDURE:

  34. LEEP/LLETZ OUTCOME:

  35. Let us prevent another epidemic—SCREEN/TREAT! • Cervical Cancer screening/treatment imperative! • HIV seropositive women are living longer now RLC • Preventable cancer • Beginning to see cancer in women under 40 years of age • HIV positive women need screening don’t wait till 30

  36. “Every woman has the right to live a life free from cervical cancer”

  37. Thank You

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