Atypical clinical behavior of p16-confirmed HPV-related oropharyngeal squamous cell carcinoma treated with radical radiotherapy.
OBJECTIVE
To report atypical clinical behavior observed in human papillomavirus (HPV)-related oropharyngeal carcinoma (OPC) treated with radiotherapy.


METHODS
A retrospective cohort study was conducted for all newly diagnosed OPC cases treated with radiotherapy on July 1, 2003 to April 30, 2009. HPV positivity was determined by p16 immunostaining in tumors. The incidence of additional malignancies and the pattern of distant metastases (DMs) were compared between the HPV-positive (HPV+) and HPV-negative (HPV-) cohorts.


RESULTS
HPV status was evaluated in 318 of 613 consecutive OPC cases (52%), showing 236 HPV+ and 82 HPV- patients. Compared with HPV-, HPV+ cases were less likely to have additional malignancies (prior: 11% vs. 20%, p = 0.038; synchronous: 1% vs. 9%, p = 0.001; metachronous: 6% vs. 16%, p = 0.003). Whereas the majority (10 of 12) of HPV- additional head-and-neck (HN) mucosal malignancies were in the oral cavity, there was none (0 of 7) in the HPV+ cohort (p < 0.001). HPV+ synchronous HN second primaries (SPs) were in the supraglottis, post-cricoid, and nasopharynx; metachronous HN SPs were in the glottis, supraglottis, and ethmoid plus glottis/post-cricoid region. All SPs that could be tested were HPV+. There was no difference in DM rate (10% vs. 15%, p = 0.272), but HPV+ DMs were more likely to involve multiple organs (46% vs. 0%, p = 0.005) and unusual sites.


CONCLUSIONS
This study reports atypical clinical behavior seen in HPV+ OPC, including multicentric lesions in HN mucosa and DM to multiple organs and unusual sites. The frequency of these events is low, but they may have clinical implications. The routine assessment of HPV status for all OPC is warranted.
Department of Radiation Oncology, Princess Margaret Hospital/University of Toronto, Toronto, Ontario, Canada.
Shao Hui
SH
Huang
Bayardo
B
Perez-Ordonez
Fei-Fei
FF
Liu
John
J
Waldron
Jolie
J
Ringash
Jonathan
J
Irish
Bernard
B
Cummings
Lillian L
LL
Siu
John
J
Kim
Ilan
I
Weinreb
Andrew
A
Hope
Patrick
P
Gullane
Dale
D
Brown
Willa
W
Shi
Brian
B
O'Sullivan
D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000428:Alcohol Drinking / Q000009:adverse effects; D014408:Biomarkers, Tumor / Q000032:analysis*; D002294:Carcinoma, Squamous Cell / Q000473:pathology / Q000532:radiotherapy / Q000556:secondary / Q000821:virology*; D015331:Cohort Studies; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000032:analysis*; D004279:DNA, Viral / Q000302:isolation & purification; D005260:Female; D006258:Head and Neck Neoplasms / Q000473:pathology / Q000532:radiotherapy / Q000821:virology; D052162:Human papillomavirus 16 / Q000235:genetics / Q000302:isolation & purification*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000473:pathology / Q000532:radiotherapy / Q000821:virology; D009378:Neoplasms, Multiple Primary / Q000473:pathology / Q000532:radiotherapy / Q000821:virology*; D016609:Neoplasms, Second Primary / Q000473:pathology / Q000532:radiotherapy / Q000821:virology*; D009959:Oropharyngeal Neoplasms / Q000473:pathology / Q000532:radiotherapy / Q000821:virology*; D030361:Papillomavirus Infections / Q000150:complications / Q000821:virology*; D012189:Retrospective Studies; D012907:Smoking / Q000009:adverse effects
D014408:Biomarkers, Tumor; D019941:Cyclin-Dependent Kinase Inhibitor p16; D004279:DNA, Viral