Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Weiland, T.
Detection of serological HPV16 L1 status in patients with oropharyngeal carcinoma.
Doktoratsstudium der Medizinischen Wissenschaft; Humanmedizin; [ Dissertation ] Graz Medical University ; 2020. pp. 130
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- Autor*innen der Med Uni Graz:
- Betreuer*innen:
- Mokry Michael
- Thurnher Dietmar
- Tomazic Peter Valentin
- Altmetrics:
- Abstract:
- Introduction Although demonstrably associated with better therapy response and survival rates, the majority of HPV-induced oropharyngeal squamous cell carcinomas (OPSCCs) are still primarily diagnosed at advanced tumor stages significantly reducing patients’ prognosis. Since cell-based screening methods compared to the pap-smear test in cervical carcinoma were proven to be unsuitable in OPSCC, attempts to develop reliable blood-based assays for detection of antibodies to relevant HPV-antigens became the focus of scientific interest. This study aims to assess the clinical performance of a newly developed HPV16-L1 DRH1 epitope-specific serological assay. Material and Methods In a prospective observational study, sera of 34 HNSCC patients and 1064 healthy controls were analyzed for the presence of HPV16-L1 antibodies using a novel subtype-specific competitive immunoassay based on the monoclonal mouse antibody DRH1. In the HNSCC cohort, serum samples were collected prior to treatment and in intervals of 3 to 6 months between september 2016 and November 2018 during clinical follow-up which was performed according to national guidelines including careful physical examination, soft tissue sonography of the neck and further imaging (CT/MRI) if indicated. HPV tumor status was analyzed by PCR-based detection of HPV-DNA including genotyping and p16 immunohistochemistry (ICH). Results The evaluated immunoassay showed a sensitivity of 95% (95% CI 77.2 – 99.9%) and an associated positive predictive value of 45.65% for HPV16-driven HNSCCs. On the basis of the healthy cohort, overall diagnostic specificity was calculated with 99.46% for men and 99.29% for women > 30 years of age. During serological follow-up, a decrease of antibody titers between 30 to 100% was observed in the majority of HPV16-driven HNSCC patients living disease free of up to 26 months. In one case, a sudden rise of antibody titer during follow-up was linked to tumor recurrence in the lungs. Conclusion It was shown for the first time that the specific detection of antibodies to HPV16-L1 is indicative for the course of HPV16-induced HNSCC. On the basis of its high sensitivity and specificity, the evaluated immunoassay seems to be a promising tool to reliably identify relevant HPV16-related disease and might be useful for measuring treatment response and disease control along follow- up.