Human papillomavirus infection in oral verrucous carcinoma: genotyping analysis and inverse correlation with p53 expression.
OBJECTIVE
Verrucous carcinoma (VC) is a rare subtype of squamous cell carcinoma, occurring mostly in oral mucosa. To clarify the role of human papillomavirus (HPV) in VC tumorigenesis, we investigated localization and genotypes of HPV and p53 expression in oral VC.


METHODS
We studied paraffin-embedded specimens of 23 VCs and 10 control non-neoplastic lesions in oral mucosa. To investigate HPV infection, HPV genotypes and p53 expression, we respectively employed in situ hybridization (ISH), sequence analysis following short PCR fragment-PCR assay and immunohistochemistry.


RESULTS
Of the 23 VC specimens, 11 (48%) had HPV-DNA (detectable by PCR), and 6 (26%) had intranuclear HPV in the upper portion of the squamous epithelium (detectable by ISH). Nine of the 11 PCR-positive specimens showed multiple infections with low- and high-risk HPVs. No HPV-16 infection was detected. Although HPV-6 and HPV-18 were frequently detected by PCR, no HPV could be found in control specimens by ISH. p53 expression was inversely correlated with HPV infection.


CONCLUSIONS
Thus, multiple infections with low- and high-risk HPVs and their rapid replication during hyperkeratinization may participate in the histogenesis of oral VC. Oral VC tumorigenesis may involve the inactivation of p53, which is associated with HPV infection.
Fujita
Shuichi
S
Division of Oral Pathology and Bone Metabolism, Unit of Basic Medical Sciences, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan. fujishu@nagasaki-u.ac.jp
Senba
Masachika
M
Kumatori
Atsushi
A
Hayashi
Tomayoshi
T
Ikeda
Tohru
T
Toriyama
Kan
K
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018289:Carcinoma, Verrucous / Q000378:metabolism* / Q000473:pathology / Q000821:virology*; D016022:Case-Control Studies; D002648:Child; D004273:DNA, Neoplasm / Q000235:genetics; D004279:DNA, Viral / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005838:Genotype; D052161:Human papillomavirus 18 / Q000235:genetics / Q000472:pathogenicity; D052163:Human papillomavirus 6 / Q000235:genetics / Q000472:pathogenicity; D006801:Humans; D017403:In Situ Hybridization; D008297:Male; D008875:Middle Aged; D009061:Mouth Mucosa / Q000378:metabolism / Q000473:pathology / Q000821:virology; D009062:Mouth Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000821:virology*; D030361:Papillomavirus Infections / Q000150:complications* / Q000175:diagnosis; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
D004273:DNA, Neoplasm; D004279:DNA, Viral; D016159:Tumor Suppressor Protein p53