Physical status of HPV-16 in esophageal squamous cell carcinoma.
BACKGROUND
Infection with high-risk human papillomavirus (HPV) has been implicated as one of the risk factors of esophageal squamous cell carcinoma (ESCC). Integration of viral DNA into host genome is essential for carcinogenesis since it promotes disruption of the HPV E2 gene, leading to abnormal expression of E6 and E7 oncoproteins.


OBJECTIVE
To investigate the viral integration status of HPV-16 infection in ESCC, 35 HPV-positive ESCC specimens collected from Chinese patients were subject to real-time quantitative PCR for determination of physical status of HPV-16 by analyzing the ratios of E2 to E6 genes.


RESULTS
Our results showed that only 8.6% (3/35) of the HPV-16 positive specimens harbored exclusively the episomal form (i.e. E2/E6 ratio > or = 1), whereas the remaining 91.4% contained either only the integrated form (5.7%, with E2/E6 ratio = 0) or a mixture of episomal and integrated forms of viral molecules (85.7%, with E2/E6 ratios > 0 but < 1). Amongst the 30 cancer specimens carrying mixed integrated and episomal forms, 28 had E2/integrated E6 ratios of less than 1, indicating a predominance of integrated form of viral genes in these lesions.


CONCLUSIONS
Our finding of frequent integration of viral DNA in the host genome suggests that integration HPV-16 is common in ESCC from Chinese patients and implies that HPV infection may play a role in the pathogenesis of ESCC.
Si
Hua Xin
HX
Department of Anatomy, The University of Hong Kong, Faculty of Medicine Building, 21 Sassoon Road, Pokfulam, Hong Kong SAR, PR China.
Tsao
Sai Wah
SW
Poon
Cycles Suet Ping
CS
Wong
Yong Chuan
YC
Cheung
Annie Lai Man
AL
D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000473:pathology / Q000821:virology*; D004268:DNA-Binding Proteins / Q000235:genetics; D004938:Esophageal Neoplasms / Q000235:genetics / Q000473:pathology / Q000821:virology*; D006801:Humans; D009856:Oncogene Proteins, Viral / Q000235:genetics; D027383:Papillomaviridae / Q000145:classification / Q000235:genetics* / Q000302:isolation & purification; D030361:Papillomavirus Infections / Q000150:complications; D012097:Repressor Proteins / Q000235:genetics; D016662:Virus Integration / Q000235:genetics*
D004268:DNA-Binding Proteins; C054855:E2 protein, Human papillomavirus type 16; C068651:E6 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral; D012097:Repressor Proteins