Integration of human papillomavirus 16 in esophageal carcinoma samples

Abstract

BackgroundEsophageal carcinoma (EC) is one of the major cancers in China. In 1982, Syrjanen first hypothesized the relationship between human papillomavirus (HPV) infection and the development of esophageal cancer. Since then, many reports in the field have supported this viewpoint. This study investigated the etiological relationship between HPV infection and the occurrence of esophageal carcinoma at Tangshan City of the Hebei province in China.Methods189 samples of esophageal carcinoma patients were collected. DNA and RNA were isolated from samples, HPV DNA was detected by polymerase chain reaction (PCR) using My09/11 for HPV L1, and HPV16 was determined using type-specific primer sets for HPV16 E6. The HPV16 integration site was verified by amplification of papillomavirus oncogene transcripts, and HPV16 oncogene transcript products were ligated to the pMD-18 T vector and sequenced to confirm the physical location of HPV16 integration.Results168 HPV-positive samples were detected in 189 samples, and among them 76 specimens were HPV16 positive. Approximately 600 bp of the HPV16 oncogene transcript were detected in nine esophageal cancer samples. Sequence analysis revealed that HPV16 E7 integrated into human chromosome 2 in three samples, into human chromosome 5 in one sample, into human chromosome 6 in one sample, into human chromosome 8 in two samples, and into human chromosome 17 in two samples. The results verified that the integrated HPV16 E7 in five samples harbored one mutation of viral DNA compared with the HPV16 sequence provided in GenBank (K02718).ConclusionsThe high prevalence of HPV16 suggests that HPV16 may play an etiological role in the development of esophageal cancer. The integration of HPV16 into host cell chromosomes suggests that persistent HPV infection is key for esophageal epithelial cell malignant transformation and carcinogenesis.

ViMIC: A Database of Human Disease-related Virus Mutations, Integration Sites and Cis-effects

“…Understanding of viral pathogenic mutations will abet the effective surveillance and early detection for the high-risk virus-infected diseases. The significant viral mutations or regions for affecting integration reactions have also been reported (10,11,13,25).…”

Water Carcinogenicity and Prevalence of HPV Infection in Esophageal Cancer Patients in Huaihe River Basin, China

“…HPV16 was also found integrated into human chromosomes. The relationship of HPV high-risk types with gastrointestinal cancers is documented in recent studies from Iran and China [21, 22]. …”

Esophageal squamous cell carcinomas in a Malaysian cohort show a lack of association with human papillomavirus

“…If so, this is a crucial inference for the future understanding of esophageal cancers. Nevertheless, the continued reports of cases of HPV‐associated ESCC and the detection of HPV16 in the cancer of one patient in this study still merit consideration. This is especially the case when HPV16 was detected using two separate methods, and at an intermediate titer by the real‐time PCR.…”

“…Adding to this ongoing intriguing situation, two recent reports have put forward some new angles for the so‐far tenuous relationship between HPV and esophageal cancers. Li et al's finding of HPV16 E7 integrated into the esophageal cancer genome is very interesting and should herald further interrogation along this line . Similarly, another group's report that HPV is detected with equal frequency in their patients with ESCC and the normal esophageal tissue of volunteers presents yet another perspective to consider in this problem…”

“…Li et al's finding of HPV16 E7 integrated into the esophageal cancer genome is very interesting and should herald further interrogation along this line. 14 Similarly, another group's report that HPV is detected with equal frequency in their patients with ESCC and the normal esophageal tissue of volunteers presents yet another perspective to consider in this problem. 15 In our Malaysian context there are no published data on the incidence of HPV in esophageal cancers to date.…”