Format

Send to

Choose Destination
Oral Oncol. 2018 Mar;78:137-144. doi: 10.1016/j.oraloncology.2018.01.010. Epub 2018 Feb 20.

Double positivity for HPV-DNA/p16ink4a is the biomarker with strongest diagnostic accuracy and prognostic value for human papillomavirus related oropharyngeal cancer patients.

Author information

1
Cancer Epidemiology Research Program, Catalan Institute of Oncology (ICO), IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain; Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Madrid, Spain. Electronic address: mmena@iconcologia.net.
2
Cancer Epidemiology Research Program, Catalan Institute of Oncology (ICO), IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain; Department of Medical Oncology, Catalan Institute of Oncology (ICO), ONCOBELL, IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain; University of Barcelona, Barcelona, Spain.
3
Cancer Epidemiology Research Program, Catalan Institute of Oncology (ICO), IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain; Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Madrid, Spain.
4
Cancer Epidemiology Research Program, Catalan Institute of Oncology (ICO), IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain.
5
Department of Pathology, Hospital del Mar, Barcelona, Spain.
6
Department of Pathology, Hospital General de l'Hospitalet, Barcelona, Spain.
7
Department of Otorhinolaryngology, Hospital de Sant Pau, Barcelona, Spain; Centro de Investigación Biomédica en Red de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Madrid, Spain.
8
Department of Otorhinolaryngology, Hospital de Sant Pau, Barcelona, Spain.
9
Department of Pathology, Hospital de Sant Pau, Barcelona, Spain.
10
Department of Medical Oncology, Catalan Institute of Oncology (ICO), ONCOBELL, IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain; University of Barcelona, Barcelona, Spain; Department of Medical Oncology, Catalan Institute of Oncology (ICO), Badalona, Barcelona, Spain.
11
Department of Otorhinolaryngology, Hospital Universitari Bellvitge, L'Hospitalet de Llobregat, Barcelona, Spain.
12
Department of Pathology, Hospital Universitari Bellvitge, L'Hospitalet de Llobregat, Barcelona, Spain.
13
Department of Otorhinolaryngology, Hospital Universitari Parc Taulí, Sabadell, Barcelona, Spain.
14
Department of Medical Oncology, Hospital Universitari Parc Taulí, Sabadell, Barcelona, Spain.
15
Department of Pathology, Hospital Universitari Parc Taulí, Sabadell, Barcelona, Spain.
16
Cancer Research Program, IMIM, Hospital del Mar, Barcelona, Spain; Department of Medical Oncology, Hospital del Mar, Barcelona, Spain.
17
Department of Otorhinolaryngology, Hospital del Mar, Barcelona, Spain.
18
Division of Molecular Diagnostics of Oncogenic Infections, Infection, Inflammation and Cancer Program, German Cancer Research Center (DKFZ), Heidelberg, Germany.
19
Laboratory MIVEGEC (UMR CNRS 5290, IRD 224, UM), French National Center for Scientific Research (CNRS), Montpellier, France.
20
Cancer Epidemiology Research Program, Catalan Institute of Oncology (ICO), IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain; Epidemiology and Public Health, Centro de Investigación Biomédica en Red: Epidemiología y Salud Pública (CIBERESP), Instituto de Salud Carlos III, Madrid, Spain.
21
Cancer Epidemiology Research Program, Catalan Institute of Oncology (ICO), IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain; Epidemiology and Public Health, Centro de Investigación Biomédica en Red: Epidemiología y Salud Pública (CIBERESP), Instituto de Salud Carlos III, Madrid, Spain. Electronic address: lalemany@iconcologia.net.

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 p16INK4a/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 p16INK4a, HPV-DNA, HPV-DNA/HPV-E6*I mRNA, and HPV-DNA/p16INK4a, respectively. Being non-smoker 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/p16INK4a showed strongest diagnostic accuracy and prognostic value.

CONCLUSIONS:

Double positivity for HPV-DNA/p16INK4a, 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.

KEYWORDS:

Diagnostic accuracy; Human papillomavirus; Oropharyngeal cancer; Prognosis markers; Survival

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center