Annals of Surgical Oncology

, Volume 20, Supplement 3, pp 450–458

HPV Status of Oropharyngeal Cancer by Combination HPV DNA/p16 Testing: Biological Relevance of Discordant Results

Authors

    • Department of Radiation OncologyRoyal Prince Alfred Hospital
    • Sydney Medical SchoolThe University of Sydney
  • Deanna Jones
    • Department of Infectious Diseases and Immunology, Central Clinical SchoolThe University of Sydney
  • Mark Chatfield
    • NHMRC Clinical Trials CentreThe University of Sydney
  • C. Soon Lee
    • Discipline of Pathology, School of MedicineUniversity of Western Sydney
    • Department of Anatomical PathologyLiverpool Hospital
    • Cancer Pathology, Bosch Institute, The University of Sydney and Dept of Anatomical PathologyRoyal Prince Alfred Hospital
  • Mei Zhang
    • Department of Radiation OncologyRoyal Prince Alfred Hospital
    • Sydney Medical SchoolThe University of Sydney
    • Department of Infectious Diseases and Immunology, Central Clinical SchoolThe University of Sydney
  • Jonathan Clark
    • Sydney Head and Neck Cancer InstituteRoyal Prince Alfred Hospital
  • Michael Elliott
    • Sydney Medical SchoolThe University of Sydney
    • Sydney Head and Neck Cancer InstituteRoyal Prince Alfred Hospital
  • Gerald Harnett
    • Pathwest Laboratory MedicineQEII Medical Centre
  • Christopher Milross
    • Department of Radiation OncologyRoyal Prince Alfred Hospital
    • Sydney Medical SchoolThe University of Sydney
  • Barbara Rose
    • Department of Infectious Diseases and Immunology, Central Clinical SchoolThe University of Sydney
    • Sydney Head and Neck Cancer InstituteRoyal Prince Alfred Hospital
Translational Research and Biomarkers

DOI: 10.1245/s10434-012-2778-4

Cite this article as:
Hong, A., Jones, D., Chatfield, M. et al. Ann Surg Oncol (2013) 20: 450. doi:10.1245/s10434-012-2778-4

Abstract

Background and Purpose

Human papillomavirus (HPV) causes up to 70 % of oropharyngeal cancers (OSCC). HPV positive OSCC has a more favorable outcome, thus HPV status is being used to guide treatment and predict outcome. Combination HPV DNA/p16ink4 (p16) testing is commonly used for HPV status, but there are no standardized methods, scoring or interpretative criteria. The significance of discordant (HPV DNA positive/p16 negative and HPV DNA negative/p16 positive) cancers is controversial. In this study, 647 OSCCs from 10 Australian centers were tested for HPV DNA/p16 expression. Our aims are to determine p16 distribution by HPV DNA status to inform decisions on p16 scoring and to assess clinical significance of discordant cancers.

Methods

HPV DNA was identified using a multiplex tandem HPV E6 polymerase chain reaction (PCR) assay and p16 expression by semiquantitative immunohistochemistry.

Results

p16 distribution was essentially bimodal (42 % of cancers had ≥70 % positive staining, 52 % <5 % positive, 6 % between 5 and 70 %). Cancers with 5 to <50 % staining had similar characteristics to the p16 negative group, and cancers with 50 to <70 % staining were consistent with the ≥70 % group. Using a p16 cut-point of 50 %, there were 25 % HPV DNA positive/p16 negative cancers and 1 % HPV DNA negative/p16 positive cancers. HPV DNA positive/p16 negative cancers had outcomes similar to HPV DNA negative/p16 negative cancers.

Conclusions

50 % is a reasonable cut-point for p16; HPV DNA positive/p16 negative OSCCs may be treated as HPV negative for clinical purposes; HPV DNA/p16 testing may add no prognostic information over p16 alone.

Supplementary material

10434_2012_2778_MOESM1_ESM.docx (20 kb)
Supplementary material 1 (DOCX 20 kb)

Copyright information

© Society of Surgical Oncology 2012