The relationship of human papillomavirus to proliferation and ploidy in carcinoma of the anus.
BACKGROUND
Human papillomavirus (HPV) infections have been implicated in anogenital neoplasia in both sexes. In this study, the authors postulated that HPV infections induce squamous epithelium to become hyperproliferative and aneuploid.


METHODS
To test this hypothesis, formalin fixed, paraffin embedded tissues were analyzed for the presence of HPV by in situ hybridization. S-phase fraction and DNA content were evaluated by flow cytometry. Proliferative indices also were analyzed using an antibody to proliferating cell nuclear antigen (PCNA).


RESULTS
Human papillomavirus DNA was present in 48.1% of the carcinomas. All but one HPV-positive tumor contained HPV 16/18 DNA. The remaining tumor contained only HPV 6/11. No correlation was found between HPV status, patient age, or tumor differentiation. Thirty-three percent of tumors were aneuploid. Only two patients had aneuploid tumors that were HPV-negative; these patients received preoperative radiotherapy. The average S-phase fraction was significantly higher (P < 0.01) in HPV-positive versus HPV-negative lesions. The PCNA index for HPV positive tumors was also significantly higher than that observed in negative tumors (p < 0.003).


CONCLUSIONS
The presence of HPV in tumor cells is significantly associated with an increased proliferative rate and aneuploid status of tumors compared with HPV-negative tumors. These findings are consistent with the fact that viral proteins binding to tumor suppressor gene proteins can deregulate the cell cycle and lead to genomic instability.
Department of Pathology and Laboratory Medicine, University of Cincinnati College of Medicine, OH 45267-0529.
A E
AE
Noffsinger
Y Z
YZ
Hui
L
L
Suzuk
L K
LK
Yochman
M A
MA
Miller
P
P
Hurtubise
A A
AA
Gal
C M
CM
Fenoglio-Preiser
D000782:Aneuploidy; D001005:Anus Neoplasms / Q000235:genetics / Q000473:pathology / Q000821:virology*; D001483:Base Sequence; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000473:pathology / Q000821:virology*; D002455:Cell Division; D004273:DNA, Neoplasm; D004279:DNA, Viral / Q000032:analysis*; D006801:Humans; D017403:In Situ Hybridization; D008969:Molecular Sequence Data; D027383:Papillomaviridae / Q000235:genetics / Q000302:isolation & purification*; D016133:Polymerase Chain Reaction
D004273:DNA, Neoplasm; D004279:DNA, Viral