Molecular etiology of second primary tumors in contralateral tonsils of human papillomavirus-associated index tonsillar carcinomas.
OBJECTIVE
For patients with tobacco-related head and neck squamous cell carcinoma (HNSCC), the occurrence of a second primary tumor (SPT) is an ominous development that is attributed to a field cancerization effect and portends a poor clinical outcome. The goal of this study was to determine whether patients with human papillomavirus (HPV)-related index tonsillar carcinomas can also develop SPTs in the contralateral tonsil, and to discern the molecular etiology of HPV-related tumor multifocality.


METHODS
The surgical pathology archives of The Johns Hopkins Hospital were searched for all patients with primary HPV-related tonsillar squamous cell carcinoma who developed a synchronous or metachronous carcinoma in the contralateral tonsil. The HPV-16 E6 exon was sequenced from each independent cancer site to determine whether the tumor pairs harbored the same or a different HPV-16 variant.


RESULTS
Four patients with bilateral HPV-related tonsillar carcinomas were identified. In every case, the HPV DNA sequences derived from the index tumor and corresponding SPT were 100% concordant, indicating that the index and SPTs were caused by the same HPV-16 variant.


CONCLUSIONS
For the small subset of patients with tonsillar carcinomas who develop SPTs in the contralateral tonsil, the index case and the SPT consistently harbored the same HPV variant. This finding suggests that HPV-related tumor multi-focality can be attributed either to independent inoculation events by the same virus, or by migration of HPV-infected cells from a single inoculation site to other regions of Waldeyer's ring.
Department of Otolaryngology - Head and Neck Surgery, Johns Hopkins Medical Institutions, Baltimore, MD 21287, USA.
Andrew W
AW
Joseph
Takenori
T
Ogawa
Justin A
JA
Bishop
Sofia
S
Lyford-Pike
Xiaofei
X
Chang
Timothy H
TH
Phelps
William H
WH
Westra
Sara I
SI
Pai
D000328:Adult; D000368:Aged; D002278:Carcinoma in Situ / Q000821:virology; D002294:Carcinoma, Squamous Cell / Q000821:virology*; D059248:Chemoradiotherapy; D004279:DNA, Viral / Q000032:analysis; D018572:Disease-Free Survival; D005091:Exons / Q000235:genetics; D005500:Follow-Up Studies; D014644:Genetic Variation / Q000235:genetics; D052162:Human papillomavirus 16 / Q000235:genetics*; D006801:Humans; D017403:In Situ Hybridization; D008297:Male; D008875:Middle Aged; D037981:Neck Dissection; D020360:Neoadjuvant Therapy; D009378:Neoplasms, Multiple Primary / Q000821:virology; D016609:Neoplasms, Second Primary / Q000821:virology*; D009856:Oncogene Proteins, Viral / Q000235:genetics; D030361:Papillomavirus Infections / Q000821:virology*; D011505:Protein-Tyrosine Kinases / Q000235:genetics; D018714:Radiotherapy, Adjuvant; D012097:Repressor Proteins / Q000235:genetics; D012189:Retrospective Studies; D014067:Tonsillar Neoplasms / Q000821:virology*; D014068:Tonsillectomy
D004279:DNA, Viral; C068651:E6 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral; D012097:Repressor Proteins; D011505:Protein-Tyrosine Kinases