HPV Genotyping and Site of Viral Integration in Cervical Cancers in Indian Women

Abstract

Persistent HPV infection plays a major role in cervical cancer. This study was undertaken to identify HPV types in a cohort of Indian women with locally advanced cervical cancer as well as to determine the physical state and/or site of viral integration in the host genome. Pretreatment biopsies (n = 270) from patients were screened for HPV infection by a high throughput HPV genotyping assay based on luminex xMAP technology as well as MY09/11 PCR and SPF1/2 PCR. Overall HPV positivity was observed to be 95%, with HPV16 being most common (63%) followed by infection with HPV18. Integration status of the virus was identified using Amplification of Papillomavirus Oncogene Transcripts (APOT) assay in a subset of samples positive for HPV16 and/or HPV18 (n = 86) and with an adequate follow-up. The data was correlated with clinical outcome of the patients. Integration of the viral genome was observed in 79% of the cases and a preference for integration into the chromosomal loci 1p, 3q, 6q, 11q, 13q and 20q was seen. Clinical data revealed that the physical state of the virus (integrated or episomal) could be an important prognostic marker for cervical cancer.

Physical Status and Variant Analysis of Human Papillomavirus 16 in Women from Shanghai

“…The episomal form was also found in a patient with advanced-stage cancer (SCC IIb), which is consistent with a previous study claiming that the episomal virus existed in cervical tumors [25,26]. This finding indicates that other factors might contribute to the lesion progression aside from HPV integration [27,28]. …”

Integrated HPV genomes tend to integrate in gene desert areas in the CaSki, HeLa, and SiHa cervical cancer cell lines

“…Whether the HPV insertion loci are randomly or regularly distributed in human genome has been widely discussed but remains unclear [11,15,23,31,37]. Theoretically, highly successful integration should lead to persistent expression of viral proteins that is sufficiently robust to induce malignancy.…”

Mate pair sequencing of oropharyngeal squamous cell carcinomas reveals that HPV integration occurs much less frequently than in cervical cancer

“…The frequencies of viral integrations detected in cervical cancers are consistently high, and are observed in 100% of HPV18 positive cases and up to 80% of HPV16-positive cases [12,13]. In addition, cervical cancer patients with HPV integrations appear to be associated with a worse clinical outcome [14].…”