Viral load, E2 gene disruption status, and lineage of human papillomavirus type 16 infection in cervical neoplasia.
The clinical utility of human papillomavirus (HPV) load and integration status remains unclear. We applied refined methods to delineate the viral load, integration status, and lineage of 104 women with HPV-16 monotype infection, including 19 with normal cervices, 9 with histologically proven cervical intraepithelial neoplasia (CIN) 1, 24 with CIN 2, 27 with CIN 3, and 25 with squamous cell carcinoma (SCC). Higher crude viral load, as determined by real-time polymerase chain reaction (PCR) targeting the E7 gene, was observed for SCC but became insignificant after normalization for cell content. Integration was located and quantified by real-time PCRs targeting, respectively, the carboxyl, amino, and hinge domains of the E2 gene. Pure episomal, integrated, and mixed forms were observed in all disease groups. Most E2 gene disruptions involved the amino-terminal, but sparing the hinge region that has been frequently used as a surrogate marker of integration. Large-fragment disruption involving all 3 E2 regions was observed only in the CIN 3 and SCC groups. Altogether, 33.3% of the CIN 3 group and 28.0% of the SCC group harbored pure episomal genomes. The Asian lineage was associated with a higher risk for CIN 3/SCC than the European lineage, and 6 of the 7 large-fragment E2 disruptions were from Asian lineage. The link between viral lineage, integration pattern, and oncogenesis deserves further study.
Cheung
Jo L K
JL
Department of Microbiology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong Special Administrative Region, People's Republic of China.
Lo
Keith W K
KW
Cheung
Tak-Hong
TH
Tang
Julian W
JW
Chan
Paul K S
PK
D000293:Adolescent; D000328:Adult; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000821:virology*; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D016679:Genome, Viral; D006723:Hong Kong; D052162:Human papillomavirus 16 / Q000235:genetics / Q000502:physiology*; D006801:Humans; D008875:Middle Aged; D009856:Oncogene Proteins, Viral / Q000235:genetics*; D030361:Papillomavirus Infections / Q000821:virology*; D012720:Severity of Illness Index; D002583:Uterine Cervical Neoplasms / Q000821:virology*; D019562:Viral Load; D016662:Virus Integration; D002578:Uterine Cervical Dysplasia / Q000821:virology*
D004268:DNA-Binding Proteins; C054855:E2 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral