Aktueller Stand und Ausblick der Hamburger Screeningstudie für HPV-Oropharynxkarzinome (PHORECAST)

Introduction: Whilst the worldwide incidence of HPV-driven oropharyngeal cancer (HPV-OPC) is still increasing, early diagnosis is hampered by the lack of detectable precursor lesions. Serum antibodies against HPV16 early proteins are detectable several years before diagnosis, and cell-free HPV DNA in liquid biopsies is emerging as additional pre-diagnostic marker. PHORECAST aims defining the positive predictive value of these markers in the Hamburg City Health Study (HCHS), a single center, prospective epidemiologic cohort study that started enrolling 45,000 participants (45-74 years) in 2016.

Patients and Methods: In a proof of concept study, the sera of 4424 participants (blood draw 2016/17) were analyzed for antibodies against four HPV16 early proteins (E1, E2, E6, E7) using multiplex serology. Twelve participants (0.3%) that were seropositive for E6 and at least one additional early protein were considered at high risk for HPV-OPC development and invited to six-monthly head and neck follow-up (FU) exams starting in 2019.

Results: Two "high risk" participants were lost to follow-up. Of the remaining 10 participants 5 were diagnosed with a stage I HPV-OPC (4x pT2 pN1 cM0, 1x pT1 pN0 cM0) during the study so far and treated according to international guidelines.

Conclusion and outlook: According to the presented results, the applied method allows identifying HPV-OPC patients at an early stage. Within PHORECAST, we will further validate and improve this approach through 1) an increased number of participants screened, 2) expanding the screening population to participants who are solely E6 positive, and 3) including emerging markers, such as cell-free HPV DNA, HPV DNA in oral gargle samples, and exosomes in plasma and saliva.

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