Expanded evaluation of markers of human papillomavirus (HPV) infection and cancer at multiple anatomic sites - using PLCO data to bolster the cohort consortium effort
There are two aims in this proposal, which build on our existing research on HPV16 E6 as a promising biomarker for HPV16-driven oropharynx cancer. First, we aim to expand upon the PLCO finding that 48% of 46 incident oropharynx cancers had evidence of HPV16 E6 antibody positivity prior to diagnosis by testing all serial samples from all oropharynx cases (and any other HPV16 E6 seropositive individuals). This aim will address the hypothesis that HPV16 E6 seropositivity is present years before diagnosis of oropharyngeal cancer and assess how the titer levels vary prior to diagnosis in seropositive cases.
To better understand this potential marker, I aim to evaluate its utility in the prediction of other cancers known to be caused, at least in part, by HPV16 infection. Specifically, I will evaluate the risk conferred by serologic evidence HPV infection on anogenital cancer, including cancers of the anus, penis, vagina, vulva and cervix, by conducting a case-control study nested within PLCO and multiple cohorts. This study will address the hypothesis that HPV16 E6 antibodies are a specific marker of HPV infection within the oropharynx (compared to HPV infection at other anatomic sites) given the proximity of oral HPV infection to the highly-immunogenic lymphoid tissue of the tonsils, and that the HPV16 E6 seroprevalence will be higher among cases with oropharyngeal cancer compared to those with anogenital cancer.
Mattias Johannson (IARC)
Michael Pawlita (DKFZ)
Paul Brennan (IARC)
Allan Hildesheim (NCI, DCEG, IIB)
Aimee Kreimer (NCI, DCEG, IIB)
- Update of nested case control study and expansion to unknown primary of the head and neck and lymph nodes
- Retesting of PLCO serum samples at higher dilution volume
- Validation of an ELISA assay to measure the HPV16 E6 antibody
Timing of HPV16-E6 antibody seroconversion before OPSCC: findings from the HPVC3 consortium.
Kreimer AR, Ferreiro-Iglesias A, Nygard M, Bender N, Schroeder L, Hildesheim A, Robbins HA, Pawlita M, Langseth H, Schlecht NF, Tinker LF, Agalliu I, Smoller SW, Ness-Jensen E, Hveem K, D'Souza G, Visvanathan K, May B, Ursin G, Weiderpass E, Giles GG, Milne RL, Cai Q, Blot WJ, Zheng W, Weinstein SJ, Albanes D, Brenner N, Hoffman-Bolton J, Kaaks R, Barricarte A, Tjønneland A, Sacerdote C, Trichopoulou A, Vermeulen RCH, Huang WY, Freedman ND, Brennan P, Waterboer T, Johansson M
Ann. Oncol. 2019 Aug 1; Volume 30 (Issue 8): Pages 1335-1343 PUBMED
Kinetics of the Human Papillomavirus Type 16 E6 Antibody Response Prior to Oropharyngeal Cancer.
Kreimer AR, Johansson M, Yanik EL, Katki HA, Check DP, Lang Kuhs KA, Willhauck-Fleckenstein M, Holzinger D, Hildesheim A, Pfeiffer R, Williams C, Freedman ND, Huang WY, Purdue MP, Michel A, Pawlita M, Brennan P, Waterboer T
J. Natl. Cancer Inst. 2017; Volume 109 (Issue 8) PUBMED