1. JENNIFER L. YOUNG, MD, MPH GRAND ROUNDS Department of Obstetrics and Gynecology Medical University of South Carolina January 25,2011 From Kilimanjaro to Charleston: How Cervical cancer screening in Africa may impact our practice in the future
2. Cervical Cancer: A Worldwide Problem Prevalence: 2,274,000 women have cervical cancer1 Incidence: 510,000 new cases each year1 14,845 United States/Canada 64,928 Europe 51,266 Eastern Asia 151,297 Southcentral Asia 39,648 Southeast Asia 21,596 Central America 67,078 AFRICA 49,025 South America 1,077 Australia/ New Zealand 1. World Health Organization. Geneva, Switzerland: World Health Organization; 2003:1–74. 2. Bosch FX, de Sanjosé S. J Natl Cancer Inst Monogr. 2003;31:3–13. Modified after Merck & Co.
3. Objectives Provide you with an understanding of the timeline and planning that goes into international research Why does a study take 3 yrs to initiate and 3 wks to complete Discuss types of HPV testing kits and differences between them Why can’t we just use what we have here? By the way, what test is that? Review the data obtained from rapid HPV testing in rural Tanzania How Arusha TZ is ahead of SC
28. Study items established Female providers preferred Women know about cervical cancer and are interested in being screened Cannot exclude the hospital staff Exam remains very embarassing for women, even health care professionals Hospice team has strong connections to community for recruitment
30. Its in the details 5 team members 2 nurses 1 translator 6 suitcases of equipment One close call with import services One not as close call with US customs 1 grand rounds on HPV and cervical cancer
35. Study items established Protocol as it stands is feasible Need community based consent process Established core Selian staff for assistance Cleaning and sterilization techniques acceptable to staff Shipping paps for US testing feasible and consistent with expected results 3 outreach lectures to community and health care workers
36.
37.
38. HPV testing: aren’t they all the same? All testing based on DNA amplification No utilize traditional PCR for this methodology Tests available include: Hybrid capture II Cervista Cervista 16,18 careHPV And others Keep in mind the goal not to determine any presence of HPV but rather to determine the likelihood that the patient has a dysplasia caused by HPV
39.
40.
41. Hybrid capture II Nucleic acid hybridization assay Target DNA hybridized with specific RNA probes In this case: 13 HPV types 16,18,33,35,39,45,51,52,58,59,68 DNA-RNA hybrids captured on a microplate with antibodies specific to these Signal detection with labelled, conjugated antibodies Emitted light measured as relative light units where 1.0 consistent with 1 pg HPV DNA/mL
43. Cervista™ Utilizes patented Invader technology Signal amplification of specific DNA sequences 14 HPV types tested HPV16, 18, 31, 33, 35,39, 45, 51, 52, 56, 58, 59, 66, and 68
44. Clinical Performance Summary of Cervista: Compared to Colposcopy/Central Histology ≥ CIN2 among Women with ASC-US Cytology Sensitivity 92.8% (64/69) 95% CI: (84.1% - 96.9%) Specificity 44.2% (558/1263) 95% CI: (41.5% - 46.9%) PPV 8.3% (64/769) 95% CI: (7.6% - 8.9%) NPV 99.1% (558/563) 95% CI: (98.1% - 99.6%) Disease Prevalence 5.2% (69/1332) Note: Among women with ASC-US cytology, there were 1.1% (15 out 1347) CervistaTM HPV HR indeterminate results with 95% CI: 0.7% to 1.8%.
45. Cervista™: Limitations Does not detect DNA of HPV low-risk types (6,11,42,43,44) Exhibits cross-reactivity to two HPV types of unknown risk An HPV positive result was observed with 5000 copies/reaction of HPV type 67 50,000 copies/reaction of HPV type 70. Does not exclude the possibility of HPV infection because very low levels of infection or sampling error may cause a false-negative result Interference was observed in cervical specimens contaminated with high levels (2%) of contraceptive jelly and/or anti-fungal creams The test has been validated for use only with cervical cytology specimens
46. Cervista vs HC2 SHENCCAST II study – China 8,435 women By ROC curves, tests are clinically equivalent
47. careHPV compared to Hybrid Capture 2 Qiao Y et al. Lancet Oncol 2008; 9: 929-936.
48. careHPV Test: New rapid HPV test developed by QIAGEN (Gaithersburg, MD) 2388 women tested in rural China 70 diagnosed with ≥ CIN2 Using diagnosis of CIN2+ as the standard Qiao Y et al. Lancet Oncol 2008; 9: 929-936.
49. Team Tanzania 2010 15 team members 3 female health care providers 3 excellent pap smear cleaners 1 study coordinator 1 scientist 2 Hospice nurses 2 nursing assistants 2 lab assistances 1 driver
50.
51. The details 4 boxes of testing equipment 20 boxes of gloves 15 tubes of KY jelly 325 thin prep paps 325 Digene careHPV tests 600 consents and 300 study intake forms 1000 glass slides 324 patients enrolled 2 facilities 1 truck
52.
53. A note on approval, consent, and recruitment IRB approval took 2 years Cancer center protocol review comm UVA IRB Selian IRB Tanzanian Government IRB (wait 4-6 months…) Edits made Repeat………………..x3! Consent Education first! Translation only or a true connection to the community
54. Recruitment Mama Makule with Dr. Peyton Taylor (Babu) Meetings held with regional pastors association Significant education regarding cervical ca and screening Screening study annouced in congregations for 3 weeks Each day brought one congretation of women Transportation provided
55.
56.
57.
58.
59.
60. Study population 324 women enrolled Average age 42 years (30-60 years) Majority in monogamous relationships 21% postmenopausal Nonsmokers
61. HPV and Pap Testing results 42/324 (12.8%) were HPV positive 7 of 42 or 16.7% were positive for ≥ CIN2 No cancers were diagnosed 1 patient diagnosed with CIN3 was negative for HPV
67. HPV genotyping implications HPV 16/18 offered in current HPV vaccinations 7/42 or 16.7% positive for HPV 16 or 18 Much lower than the anticipated 70% reduction in cervical HPV disease quoted for HPV vaccine in developed countries
68. Conclusions HPV testing remains the best option for cervical cancer screening in low resource setting careHPV shows excellent agreement with current sophisticated HPV testing methods Low prevalence of HPV types covered by current vaccination
69. Acknowledgements Dr. Peyton Taylor Dr. Mark Stoler Dr. Paul Eder QIAGEN Ms. Barbara Badman Mrs. Asha Nyanga’nyi Dr. Gweneth Lazenby Dr. Emil Mchaki Mrs. Elizabeth Makule Selian and ALMC staff
