Whole Genome Analysis of Human Papillomavirus Type 16 Multiple Infection in Cervical Cancer Patients

Jira Chansaenroj,Sukumarn Swangvaree,Yong Poovorawan,Pairoj Junyangdikul,Apiradee Theamboonlers,Anant Karalak

doi:10.7314/apjcp.2012.13.2.599

Jira Chansaenroj, Sukumarn Swangvaree + Show 4 more

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https://doi.org/10.7314/apjcp.2012.13.2.599

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Abstract

The characterization of the whole genome of human papillomavirus type 16 (HPV16) from cervical cancer specimens with multiple infections in comparison with single infection samples as the oncogenic potential of the virus may differ. Cervical carcinoma specimens positive for HPV16 by PCR and INNO-LiPA were randomly selected for whole genome characterization. Two HPV16 single infection and six HPV16 multiple infection specimens were subjected to whole genome analysis by using conserved primers and subsequent sequencing. All HPV16 whole genomes from single infection samples clustered in the European (E) lineage while all multiple infection specimens belonged to the non-European lineage. The variations in nucleotide sequences in E6, E7, E2, L1 and Long control region (LCR) were evaluated. In the E6 region, amino acid changes at L83V were related to increased cancer progression. An amino acid variation N29S within the E7 oncoprotein significantly associated with severity of lesion was also discovered. In all three domains of the E2 gene non synonymous mutations were found. The L1 region showed various mutations which may be related to conformation changes of viral epitopes. Some transcription factor binding sites in the LCR region correlated to virulence were shown on GRE/1, TEF- 1, YY14 and Oct-1. HPV16 European variant prone to single infection may harbor a major variation at L83V which significantly increases the risk for developing cervical carcinoma. HPV16 non-European variants prone to multiple infections may require many polymorphisms to enhance the risk of cervical cancer development.

Highlights

Worldwide, high-risk HPV types (HR-HPV) are the cause of cervical cancer
Cervical carcinoma specimens positive for human papillomavirus type 16 (HPV16) by PCR and INNO-LiPA were randomly selected for whole genome characterization
HPV16 European variant prone to single infection may harbor a major variation at L83V which significantly increases the risk for developing cervical carcinoma

Summary

Introduction

High-risk HPV types (HR-HPV) are the cause of cervical cancer. HPV16 is the most prevalent HPV type found in cervical cancer patients (Bosch et al, 1995). The early region includes the open reading frames E1, E2, E4, E5, E6 and E7 which are associated with multiple functions of replication, transcription, transformation and viral adaptation; the late region which covers almost 40% of the genome, is translated into the L1 and L2 capsid proteins. The functions of these two proteins are viral DNA packaging and maturation. The second one is a non-coding region (NCR) located between E5 and L2 which represents the most highly variable region (Muñoz et al, 2006; Burk et al, 2009; Smith et al, 2011)

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