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Catching up on HPV-related cancers: diagnostic advances and treatment controversies

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  1. Catching up on HPV-related cancers: diagnostic advances and treatment controversies NittayaPhanuphak, MD, PhD Thai Red Cross AIDS Research Centre Bangkok, Thailand

  2. Outline • HPV – HIV – Cancers • Screening programs to prevent cervical cancer and anal cancer • Facts and challenges when making decision to screen/treat anal pre-cancerous lesions

  3. HPV – HIV – Cancers • HAART prolongs survival of PLHIV but may have incomplete immune recovery • Lack of decline or increased incidence of HPV-related cancers among PLHIV in the HAART era Palefsky JM 2011

  4. Cervical cancer in HIV+ women SIR 8.9 for in situ cancer, 5.6 for invasive cancer Incidence per 100,000 PY Chaturvedi AK, et al. J Natl Cancer Inst 2009;101:1120-30.

  5. Anal cancer in HIV+ men and women Incidence per 100,000 PY MEN WOMEN Chaturvedi AK, et al. J Natl Cancer Inst 2009;101:1120-30.

  6. Oropharyngeal cancer in HIV+ men and women Incidence per 100,000 PY SIR 1.6 Chaturvedi AK, et al. J Natl Cancer Inst 2009;101:1120-30.

  7. HPV infection and dysplastic transformation Cancer Low-grade squamous intraepithelial lesion (LSIL) High-grade squamous intraepithelial lesion (HSIL) Normal Modified from Palefsky JM 2011

  8. Screening program and prevention of cervical cancer • Rates of cervical cancer have declined in settings where screening programs have been implemented successfully • No RCT performed prior to widespread screening program • Observational studies confirmed risk of invasive cancer in women with high-grade cervical dysplasia • Screening programs remain difficult to implement in low and middle-income settings McCredie MR, et al. Lancet Oncol 2008; 9: 425–34. McIndoe WA, et al. ObstetGynecol 1984;64:451-8.

  9. Screening program and prevention of anal cancer YES • More clinics now offer screening for anal HSIL among patients at “high risk” for anal cancer, as a strategy to prevent anal cancer, based on the etiological and pathological similarities to cervical cancer • NO • More research is needed to understand the natural history of anal HSIL and to prove the efficacy and acceptability of its treatment Pria AD, et al. AIDS 2013; 27: 1185-6. Grulich AE, et al. Sex Health 2012;9:628-31.

  10. Cervical HPV and histologic HSIL among HIV+ women SUN (US) THAILAND • Progression of CIN 3 to cervical cancer = 1 in 80 per year Prevalence(%) All histologic SIL Histologic HSIL Histologic SIL Histologic SIL Cervical cancer rate in HIV+ women = 90 / 100,000 Kojic EM, et al. Sex TransmDis 2011;38:253-9. Ramautarsing R, et al. 27thInt HPV Conf 2011, Berlin, P-32.33. Chaturvedi AK, et al. J Natl Cancer Inst 2009;101:1120-30. McCredie MR, et al. Lancet Oncol 2008;9:425-34.

  11. Anal HPV and histologic HSIL among HIV+ women SUN (US) THAILAND • Anal SIL is as common as cervical SIL • More common in women with cervical, vulvar, vaginal high-grade diseases Prevalence(%) All histologic SIL Histologic HSIL Histologic SIL Anal cancer rate in HIV+ women = 11 / 100,000 Hessol NA, et al. AIDS 2009;23:59-70. Chaithongwongwatthana S, et al. IGCS 2012. Chaturvedi AK, et al. J Natl Cancer Inst 2009;101:1120-30.

  12. Anal HPV and histologic HSIL among HIV+ and HIV- MSM Meta-analysis CHINA THAILAND Prevalence(%) • Progression rate of anal HSIL to cancer (per year) • Theoretical: HIV+ MSM = 1 in 600, HIV- MSM = 1 in 4000 • Australia (73% HIV+ MSM): 1 in 80 Prevalence(%) HIV-negative HIV-negative HIV-negative Anal cancer rate in HIV+ MSM = 78 / 100,000 and in HIV- MSM = 5 / 100,000 Phanuphak N, et al. JAIDS 2013 (In press). Phanuphak N, et al. AIDS 2013 (In press). Hu Y, et al. JAIDS 2013 (In press). Tong WWY, et al. AIDS 2013 (In press). Machalek DA, et al. Lancet Oncol. May 2012;13(5):487-500.

  13. Anal HSIL screening • No standard screening guidelines • New York State Department of Health AIDS Institute • Screen at baseline and annually for HIV+: MSM, anogenital warts, abnormal vulvar/cervical histology New York State Department of Health AIDS Institute: www.hivguidelines.orgOct 2007. Palefsky JM 2011.

  14. Need for better biomarkers for screening • Anal cytology limitation • Low sensitivity and poor correlation with histologic grading • HRA limitation • Expensive and very limited number of trained physicians/nurses • Potential HGAIN biomarkers • p16 and other cell cycle markers: immunocytochemistry • E6/E7 mRNA: flow cytometry • E6 oncoproteins: rapid test • HPV DNA detection: screening test/genotyping assay Panther LA, et al. Clin Infect Dis. 2004;38:1490-1492.

  15. Biomarkers for anal HSIL Best for prediction of disease In the future Best for detection of disease at that visit Phanuphak N, et al. (Submitted)

  16. Treatment of anal HSIL • Various “in-office” treatment options are available • Side effects are not uncommon but manageable, some concerns about long-term sexual functioning • Treatment causes regression of lesions, although no prove that it will prevent anal cancer • Recurrence rate is substantial but usually is minimal • Better treatment modalities are needed Richel O, et al. Lancet Oncol 2012;14:346-53. Fox PA. Sex Health 2012;9:628-31.

  17. Treatment of anal cancer • Combination chemoradiation as the first-line therapy • In very selected cases, local excision may be used as primary treatment, often with chemoradiation • Salvage abdominoperineal resection for persistent or recurrent anal cancers Szmulowicz UM and Wu JS. Sex Health 2012;9:593-609. SEER 2011.

  18. Do I want to screen my patient? No • More research is needed on • Natural history of anal HSIL YES • What do you want to screen for? • Anal cancer: Digital ano-rectal exam • Anal HSIL: Cytology+/-HSIL biomarkers and high-resolution anoscopy

  19. Do I want to treat anal HSIL in my patient? YES • Use treatment modalities currently available • More research is needed on • Better treatment of anal HSIL No • Frequent follow-up • More research is needed on • Natural history of anal HSIL • Anal cancer biomarkers • Better treatment of anal HSIL and its side effects

  20. Summary • HAART not reducing HPV-related cancers • Some cancers increasing • HIV+ men and women are more likely to have HSIL than HIV- men and women • High prevalence of anal HSIL in HIV+ MSM and women • Several challenges are there when considering screening programs for anal HSIL • Dependent on clinician’s interpretation of the data and readiness of the local health systems

  21. Acknowledgments HIV-NAT and SEARCH • JintanatAnanworanich • Steve Kerr • Cecilia Shikuma • ReshmieRamautarsing Srinakharinwirot University • PiamkamonVacharotayangkul Thai Red Cross AIDS Research Centre • NipatTeeratakulpisarn • PraphanPhanuphak • TippawanPankam • JiranuwatBarisri • TRC Anonymous Clinic staff • Our clinic clients & study participants Chulalongkorn University • SomboonKeelawat • SurangTriratanachat • SurasithChaithongwongwatthana • PreechaRuangvejvorachai • SarunyaNumto UCSF • Joel Palefsky TREAT Asia • Annette Sohn The AIN Biomarker Study is funded by the US NIH, through a grant to amfAR for the International Epidemiologic Databases to Evaluate AIDS (IeDEA); NIAID/NCI/NICHD, UO1AI069907.