Prevalence and expression of human papillomavirus in tonsillar carcinomas, indicating a possible viral etiology.
The presence of human papillomavirus (HPV) DNA was assessed in biopsies of tonsillar carcinomas (n = 10) and cases of tonsillitis (n = 7), serving as controls, by general-primer-mediated PCR (GP-PCR). All carcinomas appeared HPV-positive, whereas all cases of tonsillitis were HPV-negative. Additional type-specific PCR for HPV 6, 11, 16, 18, 31 and 33 revealed that 4 carcinomas contained HPV 16 DNA, 4 contained HPV 33 DNA and 1 contained an HPV 16/33 double infection. False positivity was excluded by additional Southern blot analysis of type-specific PCR-positive samples (n = 4). Further characterization of GP-PCR products by sequence analysis revealed that 2 carcinomas contained still uncharacterized HPV genotypes; one of these also contained HPV 33 DNA and one was negative by type-specific PCR. Application of RNA PCR revealed expression of HPV 16 or HPV 33 E7 encoding spliced E6*1 transcripts in all tonsillar carcinomas (n = 4) examined. Additional non-radioactive RNA in situ hybridization performed on 3 biopsies revealed the presence of HPV 16 or HPV 33 E7 transcripts exclusively localized within the carcinoma cells, whereas stroma stained negative. These findings strongly support a role for certain HPV types in the pathogenesis of tonsillar carcinomas.
Snijders
P J
PJ
Department of Pathology, Free University Hospital, Amsterdam, The Netherlands.
Cromme
F V
FV
van den Brule
A J
AJ
Schrijnemakers
H F
HF
Snow
G B
GB
Meijer
C J
CJ
Walboomers
J M
JM
D000595:Amino Acid Sequence; D001483:Base Sequence; D015139:Blotting, Southern; D004279:DNA, Viral / Q000235:genetics / Q000302:isolation & purification; D016679:Genome, Viral; D006801:Humans; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides; D027383:Papillomaviridae / Q000235:genetics / Q000302:isolation & purification*; D016133:Polymerase Chain Reaction / Q000379:methods; D015995:Prevalence; D012367:RNA, Viral / Q000032:analysis / Q000235:genetics / Q000302:isolation & purification; D015183:Restriction Mapping; D012689:Sequence Homology, Nucleic Acid; D014067:Tonsillar Neoplasms / Q000235:genetics / Q000382:microbiology* / Q000648:ultrastructure; D014158:Transcription, Genetic; D014412:Tumor Virus Infections / Q000453:epidemiology / Q000235:genetics / Q000382:microbiology* / Q000473:pathology
D004279:DNA, Viral; D009838:Oligodeoxyribonucleotides; D012367:RNA, Viral