@article {37949,
	title = {HPV16 E6/E7 expression in circulating tumor cells in oropharyngeal squamous cell cancers: A pilot study},
	journal = {PLoS.One.},
	volume = {14},
	year = {2019},
	note = {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},
	month = {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 = {analysis, Carcinoma,Squamous Cell, Dna,Viral, Female, genetics, Greece, Human papillomavirus 16, Humans, Male, Neoplasm Recurrence,Local, Neoplastic Cells,Circulating, Oncogene Proteins,Viral, Oropharyngeal Neoplasms, Papillomavirus E7 Proteins, Papillomavirus Infections, pathology, Pilot Projects, Prognosis, Repressor Proteins, RNA,Messenger, virology},
	url = {PM:31071126},
	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.}
}
