Advancing new modalities for the early detection of oropharyngeal cancer

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1 Advancing new modalities for the early detection of oropharyngeal cancer Krystle A. Lang Kuhs, PhD, MPH Assistant Professor Vanderbilt University Medical Center

2 Cancers caused by HPV 75% Oropharyngeal Cancers 100% Cervical Cancers 50% Vulvar Cancers 50% Vaginal Cancers 50% Penile Cancers 85% Anal Cancers

3 Oropharyngeal cancer Oropharynx Gillison Vaccine 2012; headandneckcancerguide.org 3

4 Rates per 100,000 Increasing rates of OPC in US 10 Oropharynx (Overall) HPV-positive Oropharynx HPV-negative Oropharynx 225% Increase HPV 1 Tobacco & Alcohol Calendar Years Adapted from: Chaturvedi et al, J Clin Onc, 2011

5 Southeast region has the highest incidence of HPV-associated OPC in the country TN Source: Rates are per 100,000 and age-adjusted to the 200 US Std. Population

6 Our region has the lowest HPV vaccination rates in the country for both girls and boys Regional Averages (2+ doses among boys) US Boys: 39% TN Boys: 26%

7 What can we do now for what will likely be a larger burden of HPV-OPC in the future? Increase HPV vaccine uptake Early detection

8 Barriers to oropharyngeal cancer screening No easily identifiable high-risk population No precursor lesion Usually small tumors buried deep within tonsillar crypts Oral paps and oral rinses lack sensitivity

9 Recent Discovery: Oropharyngeal Cancer Biomarker 1990s 2015? Looked for antibodies against HPV among: 52 oropharyngeal cancer cases 924 cancer-free matched controls 100,000 Healthy Americans Aged Donated Blood HPV16 E6 Controls N=924 Cases N=52 OR (95% CI) Seronegative 924 (99%) 30 (58%) Ref Seropositive 5 (0.5%) 22 (42%) 140 (40-491) Kreimer et al, JNCI, 2017

10 HPV16 E6 antibodies as an early marker for OPC Years from blood draw to diagnosis Kreimer et al, JNCI, 2017

11 Sensitivity and specificity of HPV16 E6 antibodies Oropharyngeal Cancer Patients (N=112) Sensitivity: >90% Serology HPV-Driven (N=87) HPV-Negative (N=25) HPV16 E6 N (%) N (%) Seropositive 78 (90%) 1 (4%) Seronegative 9 (10%) 24 (96%) Clinical Goal Standard: p16 and HPV ISH (not HPV type specific) Heathy Individuals without diagnosed cancer (N=4,666) Specificity: 99.3% Serology Cancer-free HPV16 E6 N(%) Seropositive 32 (0.7) Seronegative 4634 (99.3) Lang Kuhs KA, Cancer, In press Funding: NCI Intramural Research Award Lang Kuhs KA & Anantharaman D, et al CEBP 2015

12 HPV-ENDEAVOR HPV E6 Antibody Detection for Early Diagnosis of Vanderbilt Oropharyngeal Cancer HPV16 E6 seropositives & subset of seronegatives Test blood from healthy males aged Full Head and Neck Exam Primary Aim: Evaluate the sensitivity and specificity of HPV16 E6 serology to detect underlying undiagnosed HPV-driven oropharyngeal cancer Potential Barrier: Standard imaging modalities lack sensitivity for detecting small lesions within the oropharynx even when symptomatic Secondary Aim: Evaluate new imaging modalities for the detection oropharyngeal cancer

13 Ultrasound for the Detection of HPV-OPC Ultrasound Imaging of the Tonsil Carole Fakhry, MD, MPH Johns Hopkins University Ultrasound Imaging of the Base of Tongue

14 Advancing new modalities for the detection of HPV-OPC Head and Neck Surgeons in the Department of Otolaryngology Department of Radiology Jim Netterville Bob Sinard Sarah Rodhe Alex Langerman Kyle Mannion Young Kim Art Fleischer Joe Aulino Philips Lumify Ultrasound System Funding: VICC ACS IRG, Lang Kuhs (PI) Vanderbilt TIPS, Alvarez (PI)

15 Take Home Message The increasing incidence of and morbidity caused by HPV-driven oropharyngeal is a major public health issue, particularly in the southeast We have the tools today needed to significantly reduce the burden of this cancer in the future

16 Acknowledgements Vanderbilt University Medical Center James Lewis, Jr. James Netterville Alexander Langerman Sarah Rohde Kyle Mannion Young Kim Robert Sinard Jeremy Warner Art Fleischer Mitra Mehrad Barbara Murphy National Cancer Institute Aimée R. Kreimer Allan Hildesheim German Cancer Research Center (DKFZ) Tim Waterboer Angelika Michel Michael Pawlita Funding NCI Intramural Research Award K12 Vanderbilt Clinical Oncology Research Career Development Program Vanderbilt-Ingram Cancer Center, Early Detection and Prevention Initiative American Cancer Society Institutional Research Grant Vanderbilt Trans-Institutional Program Grant University of Pittsburgh Robert L. Ferris Sandra Gibson Nicole Schmitt Sumita Trivedi