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HPV16 E6/E7 expression in circulating tumor cells in oropharyngeal squamous cell cancers: A pilot study

Citation:

Economopoulou P, Koutsodontis G, Avgeris M, Strati A, Kroupis C, Pateras I, Kirodimos E, Giotakis E, Kotsantis I, Maragoudakis P, et al. HPV16 E6/E7 expression in circulating tumor cells in oropharyngeal squamous cell cancers: A pilot study. PLoS.One. [Internet]. 2019;14(5):e0215984.

Abstract:

OBJECTIVES: Human papillomavirus-related oropharyngeal squamous cell carcinoma (HPV+ OPSCC) is increasing in incidence. Although HPV+ OPSCC has favorable prognosis, 10 to 25% of HPV+ OPSCCs eventually recur. We sought to evaluate the feasibility of detection of HPV16 E6/E7 expression in Circulating Tumor Cells (CTCs) and its utility as a prognostic tool in HPV16-associated OPSCC. MATERIALS AND METHODS: We developed a highly sensitive RT-qPCR assay for HPV mRNA expression in EpCAM(+) CTCs. In 22 patients with early stage and locally advanced OPSCC we evaluated HPV16 E6/E7 expression in the EpCAM(+) CTC fraction at baseline and at the end of concurrent chemoradiotherapy. HPV status in pre-therapy formalin-fixed paraffin-embedded (FFPE) tumor biopsies was assessed by p16 immunohistochemistry and polymerase chain reaction (PCR) and double positives were subjected to Real-time qPCR assay for detection of HPV16, 18 and 31 types. RESULTS: Fourteen of 22 OPSCC (63.6%) were HPV DNA+/p16+. Among HPV+/p16+ patients, 10 patients (71.4%) were HPV16 DNA+. HPV16 E6/E7(+) CTCs were detected in 3 of 10 patients (30%) at baseline and 4 of 9 patients (44.4%) at the end-of-treatment, all of which were p16+/HPV16 DNA+. Survival analysis showed a significantly higher risk for disease relapse (p = 0.001) and death (p = 0.005) in patients with HPV16 E6/E7(+) baseline CTCs. CONCLUSION: Detection of HPV E6/E7(+) CTCs might be a useful noninvasive test in liquid biopsy samples for determination of a clinically relevant HPV infection in HPV+ OPSCC. Combined interpretation of HPV E6/E7(+) CTCs with UICC staging data may lead to alteration of risk definition of patient subsets, with improved risk discrimination in early-stage disease

Notes:

IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) LA - eng PT - Journal Article RN - 0 (DNA, Viral) RN - 0 (E6 protein, Human papillomavirus type 16) RN - 0 (Oncogene Proteins, Viral) RN - 0 (Papillomavirus E7 Proteins) RN - 0 (RNA, Messenger) RN - 0 (Repressor Proteins) RN - 0 (oncogene protein E7, Human papillomavirus type 16) SB - IM

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