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Title: Double positivity for HPV-DNA/p16(ink4a) is the biomarker with strongest diagnostic accuracy and prognostic value for human papillomavirus related oropharyngeal cancer patients
Author: Mena Cervigon, Maria Luisa
Taberna, Miren
Tous, Sara
Clavero, Omar
Quiros, Beatriz
Lloveras Rubio, Betlem
Alejo, Maria
Leon, Xavier
Quer, Miquel
Bague, Silvia
Mesía Nin, Ricard
Nogues, Julio
Gomà, Montse
Aguilà, Anton
Bonfill, Teresa
Blazquez, Carmen
Guix, Marta
Hijano, Rafael
Torres, Montserrat
Holzinger, Dana
Pawlita, Michael
Pavón Ribas, Miquel Àngel
Bravo, Ignacio G.
Sanjosé Llongueras, Silvia de
Bosch José, Francesc Xavier, 1947-
Alemany i Vilches, Laia
Marquez, Sandra
Keywords: Papil·lomavirus
Càncer de boca
Mouth cancer
Issue Date: 1-Mar-2018
Publisher: Elsevier Science Bv
Abstract: Background: The etiologic role of human papillomaviruses (HPV) in oropharyngeal cancer (OPC) is well established. Nevertheless, information on survival differences by anatomic sub-site or treatment remains scarce, and it is still unclear the HPV-relatedness definition with best diagnostic accuracy and prognostic value. Methods: We conducted a retrospective cohort study of all patients diagnosed with a primary OPC in four Catalonian hospitals from 1990 to 2013. Formalin-fixed, paraffin-embedded cancer tissues were subjected to histopathological evaluation, DNA quality control, HPV-DNA detection, and p16(INK4a)/pRb/p53/Cyclin-D1 immunohistochemistry. HPV-DNA positive and a random sample of HPV-DNA negative cases were subjected to HPV-E6*I mRNA detection. Demographic, tobacco/alcohol use, clinical and follow-up data were collected. Multivariate models were used to evaluate factors associated with HPV positivity as defined by four different HPV-relatedness definitions. Proportional-hazards models were used to compare the risk of death and recurrence among HPV-related and non-related OPC. Results: 788 patients yielded a valid HPV-DNA result. The percentage of positive cases was 10.9%, 10.2%, 8.5% and 7.4% for p16(INK4a), HPV-DNA, HPV-DNA/HPV-E6*I mRNA, and HPV-DNA/p16(INK4a), respectively. Being nonsmoker or non-drinker was consistently associated across HPV-relatedness definitions with HPV positivity. A suggestion of survival differences between anatomic sub-sites and treatments was observed. Double positivity for HPV-DNA/p16(INK4a) showed strongest diagnostic accuracy and prognostic value. Conclusions: Double positivity for HPV-DNA/p16(INK4a), a test that can be easily implemented in the clinical practice, has optimal diagnostic accuracy and prognostic value. Our results have strong clinical implications for patients' classification and handling and also suggest that not all the HPV-related OPC behave similarly.
Note: Versió postprint del document publicat a:
It is part of: Oral Oncology, 2018, vol. 78, p. 137-144
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Appears in Collections:Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

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