Human papillomavirus in upper digestive tract tumors from three countries.
OBJECTIVE
To clarify human papillomavirus (HPV) involvement in carcinogenesis of the upper digestive tract of virological and pathological analyses.


METHODS
The present study examined the presence of HPV in squamous cell carcinomas of the oral cavity (n = 71), and esophagus (n = 166) collected from Japan, Pakistan and Colombia, with different HPV exposure risk and genetic backgrounds. The viral load and physical status of HPV16 and HPV16-E6 variants were examined. Comparison of p53 and p16(INK4a) expression in HPV-positive and HPV-negative cases was also made.


RESULTS
HPV16 was found in 39 (55%) oral carcinomas (OCs) and 24 (14%) esophageal carcinomas (ECs). This site-specific difference in HPV detection between OCs and ECs was statistically significant (P < 0.001). There was a significant difference in the geographical distribution of HPV16-E6 variants. Multiple infections of different HPV types were found in 13 ECs, but multiple infections were not found in OCs. This difference was statistically significant (P = 0.001). The geometric means (95% confidence interval) of HPV16 viral load in OCs and ECs were 0.06 (0.02-0.18) and 0.12 (0.05-0.27) copies per cell, respectively. The expression of p16(INK4a) proteins was increased by the presence of HPV in ECs (53% and 33% in HPV-positive and -negative ECs, respectively; P = 0.036), and the high-risk type of the HPV genome was not detected in surrounding normal esophageal mucosa of HPV-positive ECs.


CONCLUSIONS
Based on our results, we cannot deny the possibility of HPV16 involvement in the carcinogenesis of the esophagus.
Department of Epidemiology and Preventive Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima 890-8544, Japan.
Andres
A
Castillo
Chihaya
C
Koriyama
Michiyo
M
Higashi
Muhammad
M
Anwar
Mulazim Hussain
MH
Bukhari
Edwin
E
Carrascal
Lida
L
Mancilla
Hiroshi
H
Okumura
Masataka
M
Matsumoto
Kazumasa
K
Sugihara
Shoji
S
Natsugoe
Yoshito
Y
Eizuru
Suminori
S
Akiba
D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000473:pathology / Q000821:virology; D002471:Cell Transformation, Neoplastic; D003105:Colombia; D004938:Esophageal Neoplasms / Q000473:pathology / Q000821:virology; D005260:Female; D052162:Human papillomavirus 16 / Q000235:genetics* / Q000472:pathogenicity; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000473:pathology / Q000821:virology; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000378:metabolism; D010154:Pakistan; D030361:Papillomavirus Infections / Q000473:pathology / Q000821:virology; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D019562:Viral Load
C068651:E6 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral; D012097:Repressor Proteins