@article {27023,
	title = {HPV16 E6/E7 expression in circulating tumor cells in oropharyngeal squamous cell cancers: A pilot study},
	journal = {PLoS One},
	volume = {14},
	number = {5},
	year = {2019},
	note = {Economopoulou, PanagiotaKoutsodontis, GeorgeAvgeris, MargaritisStrati, AretiKroupis, ChristosPateras, IoannisKirodimos, EuthymiosGiotakis, EvangelosKotsantis, IoannisMaragoudakis, PavlosGorgoulis, VassilisScorilas, AndreasLianidou, EviPsyrri, Amandaeng2019/05/10 06:00PLoS One. 2019 May 9;14(5):e0215984. doi: 10.1371/journal.pone.0215984. eCollection 2019.},
	pages = {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.},
	keywords = {Carcinoma, Squamous Cell/pathology/*virology, DNA, Viral/genetics, Female, Human papillomavirus 16/*genetics, Humans, Male, Neoplasm Recurrence, Local/genetics/virology, Neoplastic Cells, Circulating/*pathology, Oncogene Proteins, Viral/*genetics, Oropharyngeal Neoplasms/pathology/*virology, Papillomavirus E7 Proteins/*genetics, Papillomavirus Infections/pathology/virology, Pilot Projects, Prognosis, Repressor Proteins/*genetics, RNA, Messenger/genetics},
	isbn = {1932-6203 (Electronic)1932-6203 (Linking)},
	author = {Economopoulou, P. and Koutsodontis,G. and Avgeris, M. and Strati,A. and Kroupis, C. and Pateras,I. and Kirodimos,E. and Giotakis,E. and Kotsantis,I. and Maragoudakis,P. and Gorgoulis,V. and Scorilas, A. and Lianidou,E. and Psyrri, A.}
}
