Detection of High-Risk Human Papillomavirus Provides Important Diagnostic and  Prognostic Information in Oropharyngeal Cancer
Creators: Williams, Jordana R
Publisher: name: University of Alberta Library
Year: 2024

<p>The prevalence of oncogenic human papillomavirus (HPV) -related oropharyngeal squamous cell carcinoma (OPSCC) is increasing worldwide. The standard for HPV diagnosis is based on p16 immunohistochemistry (IHC) on tissues, as a surrogate marker for HPV oncogenesis in clinical and trial settings with no HPV-specific testing confirmation required.  HPV diagnosis is important because patients with HPV-related OPSCC have favorable prognoses compared to HPV-negative, due to unique pathologic and clinical characteristics that make the disease more responsive to certain treatment protocols. The problem with p16 overexpression as a surrogate biomarker is that it can be inaccurate in up to 25% of cases leading to misdiagnosis and mistreatment because p16 biomarker overexpression can occur via HPV-independent mechanisms. Furthermore, most methods of HPV detection in HNSCC including p16 IHC, require a fine needle aspirate (FNA) or tissue biopsy. </p>

<p>To address this issue, we looked at utilizing a new generation PCR technology called droplet digital PCR which is thought to be highly accurate for molecular diagnosis.  We have developed a minimally invasive rapid assay using ddPCR for the early detection of 12 high-risk (hr)- HPV in salivary swab samples.  We compared the hrHPV-ddPCR results to p16 IHC to measure concordance and diagnostic accuracy. We determined the distribution of hr-HPV types and survival outcomes according to p16 and HPV status in OPSCC. Our results showed that ddPCR was highly accurate compared to p16 IHC. Regarding HPV strains, we found that compared to HPV-16, other oncogenic strains were associated with lower survival and outcomes comparable to HPV- patients. Comparative survival analyses were performed for OPSCC participants according to p16, HPV, p16/HPV combination, HPV types and presence of multiple HPV types. P16+ (vs p16-), HPV+ (vs HPV-), p16+/HPV+ (vs p16+/HPV-, p16-/HPV+ and p16-/HPV-), HPV type 16 (vs other hr-HPV strains) and single HPV+ present (vs 2-3HPV+) all have better prognosis. Further comparative survival analyses were performed between p16+ and p16-, HPV+ and HPV- and p16/HPV combination; p16+/HPV+ vs p16+/HPV-, p16-/HPV+ and p16-/HPV-, stratified according to age, sex, smoking, T-stage, N-stage and treatment. In our cohort, the prognosis of patients with discordant p16+/HPV- depends on age, particularly 50-69, former and current smokers, T1-T3 stage, N1 stage and treatment surgery+ radiotherapy (S+RT) and surgery+ chemo radiotherapy (S+CRT).</p>

<p>The use of hr-HPV-ddPCR testing in oropharyngeal swabs is minimally invasive, highly accurate and may improve the diagnostic accuracy of HPV-OPSCC, while providing important prognostic information. This may have potential clinical applications for early diagnosis, screening during post-treatment surveillance, cases of unknown primary tumors, cases where a tissue biopsy may be difficult or prohibitive, and in resource-limited setting. It is important to detect HPV types as some strains are more aggressive.  HPV testing should be performed along with p16 IHC since discordant p16 and HPV have lower survival and HPV status may influence patient care.</p>