Background HPV causes virtually all cervical cancers HPV-16, Integration of viral oncogenes E6 and E7 Relationship between HPV and cervical cancer wou

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1 Case-Control Control Study of Human Papillomavirus avi and Oropharyngeal Cancer D Souza, DSouza, et al. NEJM, May 2007 Tony Sung Julia Beaver Journal Club September 9, 2009

2 Background HPV causes virtually all cervical cancers HPV-16, Integration of viral oncogenes E6 and E7 Relationship between HPV and cervical cancer would indicate that high-risk sexual behavior and exposure to HPV Vw will increase risk of other cancers c caused by HPV Molecular evidence supports role for HPV in pathogenesis of squamous-cell carcinomas of oropharynx

3 Background Each Year 650, patients are diagnosed with head and neck cancer and 350,000 die. 90% of these cancers are squamous-cell carcinomas. Smoking and alcohol use are main causative factors. Modulated by diet and BMI.

4 Study Outline Hypothesis: There is a causal association between HPV and oropharyngeal cancer Study Design: Case-Control Control Study Setting: Johns Hopkins Otolaryngology clinic from Participants: CASES- 100 patients with oropharyngeal cancer CONTROLS- 200 age-matched and sex-matched patients with benign conditions

5 Study Outline Data Collection: Oral-Mucosal specimens, formalin- fixed tumor specimens, snap-frozen fresh tumor specimens. ACASI interview Data analysis: In Situ hybridization of HPV-16 from formalin-fixed fixed tumors, DNA from fresh frozen and oral specimens with PCR for 37 types HPV, and antibodies to HPV-16 L1, E6 and E7 proteins via ELISA Analytic Method: multivariate logistic-regression models estimating odds ratios and associated 95% CI.

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13 Exposure to HPV and Biomarkers of Cancer

14 Exposure to HPV and Biomarkers of Cancer

15 Tobacco, Alcohol, Seropositivity and Oral Infection with HPV-16

16 Tobacco, Alcohol, Seropositivity and Oral Infection with HPV-16

17 Tobacco, Alcohol, Seropositivity and Oral Infection with HPV-16

18 Tobacco, Alcohol, Seropositivity and Oral Infection with HPV-16

19 Tobacco, Alcohol, Seropositivity and Oral Infection with HPV-16

20 Tobacco, Alcohol, Seropositivity and Oral Infection with HPV-16

21 Sexual lbehaviors

22 Sexual lbehaviors

23 Sexual lbehaviors

24 Conclusions This epidemiologic study yprovides support for the association between HPV and a subgroup of oropharyngeal cancers. We found that exposure to HPV increased the association with oropharyngeal cancer regardless of tobacco and alcohol use, but we uncovered no evidence of synergy between exposure to HPV and tobacco or alcohol use. Our data suggest that oral HPV infection is sexually acquired. Our results and those of other studies provide a rationale for HPV vaccination in both boys and girls.

25 Conclusions This epidemiologic study provides support for the association between HPV and a subgroup of oropharyngeal cancers. Case control study Absence of data on diet

26 Conclusions We found that exposure to HPV increased the association with oropharyngeal cancer regardless of tobacco and alcohol use, but we uncovered no evidence of synergy between exposure to HPV and tobacco or alcohol use. Sample size, power calculations l

27 Conclusions Our data suggest that oral HPV infection is sexually acquired. When adjusted for HPV-16 serologic status, sexual behaviors were no longer associated with oropharyngeal cancer (data not shown) Categories for number of sexual partners Cannot rule out mouth-to-mouth transmission

28 Conclusions Our results and those of other studies provide a rationale for HPV vaccination in both boys and girls. Comparison with cervical cancer

29 The End Thanks to Dr. Jeanne Clark.