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Evaluation of human papilloma virus diagnostic testing in oropharyngeal squamous cell carcinoma: sensitivity, specificity, and prognostic discrimination.

ABSTRACT: Human papillomavirus-16 (HPV16) is the causative agent in a biologically distinct subset of oropharyngeal squamous cell carcinoma (OPSCC) with highly favorable prognosis. In clinical trials, HPV16 status is an essential inclusion or stratification parameter, highlighting the importance of accurate testing.Fixed and fresh-frozen tissue from 108 OPSCC cases were subject to eight possible assay/assay combinations: p16 immunohistochemistry (p16 IHC); in situ hybridization for high-risk HPV (HR HPV ISH); quantitative PCR (qPCR) for both viral E6 RNA (RNA qPCR) and DNA (DNA qPCR); and combinations of the above.HPV16-positive OPSCC presented in younger patients (mean 7.5 years younger, P = 0.003) who smoked less than HPV-negative patients (P = 0.007). The proportion of HPV16-positive cases increased from 15% to 57% (P = 0.001) between 1988 and 2009. A combination of p16 IHC/DNA qPCR showed acceptable sensitivity (97%) and specificity (94%) compared with the RNA qPCR "gold standard", as well as being the best discriminator of favorable outcome (overall survival P = 0.002). p16 IHC/HR HPV ISH also had acceptable specificity (90%) but the substantial reduction in its sensitivity (88%) impacted upon its prognostic value (P = 0.02). p16 IHC, HR HPV ISH, or DNA qPCR was not sufficiently specific to recommend in clinical trials when used in isolation.Caution must be exercised in applying HPV16 diagnostic tests because of significant disparities in accuracy and prognostic value in previously published techniques.

SUBMITTER: Schache AG

PROVIDER: S-EPMC3188400 | biostudies-literature | 2011 Oct

REPOSITORIES: biostudies-literature

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Evaluation of human papilloma virus diagnostic testing in oropharyngeal squamous cell carcinoma: sensitivity, specificity, and prognostic discrimination.

Schache Andrew G AG Liloglou Triantafilos T Risk Janet M JM Filia Anastasia A Jones Terence M TM Sheard Jon J Woolgar Julia A JA Helliwell Timothy R TR Triantafyllou Asterios A Robinson Max M Sloan Philip P Harvey-Woodworth Colin C Sisson Daniel D Shaw Richard J RJ

Clinical cancer research : an official journal of the American Association for Cancer Research 20111001 19

<h4>Purpose</h4>Human papillomavirus-16 (HPV16) is the causative agent in a biologically distinct subset of oropharyngeal squamous cell carcinoma (OPSCC) with highly favorable prognosis. In clinical trials, HPV16 status is an essential inclusion or stratification parameter, highlighting the importance of accurate testing.<h4>Experimental design</h4>Fixed and fresh-frozen tissue from 108 OPSCC cases were subject to eight possible assay/assay combinations: p16 immunohistochemistry (p16 IHC); in si ...[more]

PMID: 21969383

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Project description:BackgroundDespite advances in the management of head and neck squamous cell carcinoma (HNSCC), prognostic models and treatment strategies remain inadequate, particularly for HPV-positive oropharyngeal squamous cell carcinoma (OPSCC). The rising incidence of HPV-positive OPSCC highlights an urgent need for innovative therapeutic approaches. Ferroptosis, a regulated form of non-apoptotic cell death, has gained attention for its role in cancer progression, but its potential as a prognostic and therapeutic target in HPV-positive OPSCC remains largely unexplored. This study investigates the role of ferroptosis in HPV-positive OPSCC, aiming to identify prognostic markers and provide insights into potential therapeutic strategies that could improve patient outcomes.MethodsThirteen ferroptosis gene expression signatures were retrieved from the literature, and their performance and association to the immune microenvironment were validated on a meta-analysis of 267 HPV-positive cases (Metanalysis-HPV267) and 286 samples from the BD2Decide project (BD2-HPV286).ResultsOur analysis revealed that specific ferroptosis-related gene expression signatures, particularly FER3, FER4, FER6, and FER12, are significantly associated (p-value < 0.05) with high-risk patient groups and adverse tumor microenvironment features, including suppressed immune activity and enhanced stromal involvement. Elevated expression of CAV1, a ferroptosis suppressor, further delineates high-risk profiles.ConclusionsThese findings highlight the prognostic significance of ferroptosis in stratifying patients and identifying those with poorer clinical outcomes. Targeting ferroptosis pathways represents a novel and promising approach to addressing the unmet need for effective prognostic and therapeutic strategies in HPV-positive OPSCC. Future research should focus on translating these findings into clinical applications to advance precision oncology and improve outcomes for this growing patient population.

Dataset Information

Evaluation of human papilloma virus diagnostic testing in oropharyngeal squamous cell carcinoma: sensitivity, specificity, and prognostic discrimination.

Publications

Evaluation of human papilloma virus diagnostic testing in oropharyngeal squamous cell carcinoma: sensitivity, specificity, and prognostic discrimination.

Similar Datasets

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