Genetic variation of <i>E6</i> and <i>E7</i> genes of human papillomavirus type 16 from central China

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Abstract

Background

Persistent high-risk human papillomavirus (HR-HPV) infection is an important factor in the development of cervical cancer, and human papillomavirus type 16 (HPV-16) is the most common HR-HPV type worldwide. The oncogenic potential of HPV-16 is closely related to viral sequence variation.

Methods

In order to clarify the variant characteristics of HPV-16 E6 and E7 genes in central China, E6 and E7 sequences of 205 HPV‐16 positive samples were amplified by polymerase chain reaction. PCR products of E6 and E7 genes were further sequenced and subjected to variation analysis, phylogenetic analysis, selective pressure analysis and B-cell epitope prediction.

Results

Twenty-six single nucleotide variants were observed in E6 sequence, including 21 non-synonymous and 5 synonymous variants. Twelve single nucleotide variants were identified in E7 sequence, including 6 non-synonymous and 6 synonymous variants. Four new variants were found. Furthermore, nucleotide variation A647G (N29S) in E7 was significantly related to the higher risk of HSIL and cervical cancer. Phylogenetic analysis showed that the E6 and E7 sequences were all distributed in A lineage. No positively selected site was found in HPV-16 E6 and E7 sequences. Non-conservative substitutions in E6, H31Y, D32N, D32E, I34M, L35V, E36Q, L45P, N65S and K75T, affected multiple B-cell epitopes. However, the variation of E7 gene had little impact on the corresponding B-cell epitopes (score < 0.85).

Conclusion

HPV-16 E6 and E7 sequences variation data may contribute to HR-HPV prevention and vaccine development in Jingzhou, central China.

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Most cited references 47

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Cervical cancer

Paul A. Cohen, Anjua Jhingran, Ana Oaknin … (2019)

Each year, more than half a million women are diagnosed with cervical cancer and the disease results in over 300 000 deaths worldwide. High-risk subtypes of the human papilloma virus (HPV) are the cause of the disease in most cases. The disease is largely preventable. Approximately 90% of cervical cancers occur in low-income and middle-income countries that lack organised screening and HPV vaccination programmes. In high-income countries, cervical cancer incidence and mortality have more than halved over the past 30 years since the introduction of formal screening programmes. Treatment depends on disease extent at diagnosis and locally available resources, and might involve radical hysterectomy or chemoradiation, or a combination of both. Conservative, fertility-preserving surgical procedures have become standard of care for women with low-risk, early-stage disease. Advances in radiotherapy technology, such as intensity-modulated radiotherapy, have resulted in less treatment-related toxicity for women with locally-advanced disease. For women with metastatic or recurrent disease, the overall prognosis remains poor; nevertheless, the incorporation of the anti-VEGF agent bevacizumab has been able to extend overall survival beyond 12 months. Preliminary results of novel immunotherapeutic approaches, similarly to other solid tumours, have shown promising results so far.

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Human papillomavirus and cervical cancer.

Mark Schiffman, Philip Castle, Jose Jeronimo … (2007)

Cervical cancer is the second most common cancer in women worldwide, and knowledge regarding its cause and pathogenesis is expanding rapidly. Persistent infection with one of about 15 genotypes of carcinogenic human papillomavirus (HPV) causes almost all cases. There are four major steps in cervical cancer development: infection of metaplastic epithelium at the cervical transformation zone, viral persistence, progression of persistently infected epithelium to cervical precancer, and invasion through the basement membrane of the epithelium. Infection is extremely common in young women in their first decade of sexual activity. Persistent infections and precancer are established, typically within 5-10 years, from less than 10% of new infections. Invasive cancer arises over many years, even decades, in a minority of women with precancer, with a peak or plateau in risk at about 35-55 years of age. Each genotype of HPV acts as an independent infection, with differing carcinogenic risks linked to evolutionary species. Our understanding has led to improved prevention and clinical management strategies, including improved screening tests and vaccines. The new HPV-oriented model of cervical carcinogenesis should gradually replace older morphological models based only on cytology and histology. If applied wisely, HPV-related technology can minimise the incidence of cervical cancer, and the morbidity and mortality it causes, even in low-resource settings.

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Is Open Access

Human papillomavirus vaccine against cervical cancer: opportunity and challenge

Renjie Wang, Wei Pan, Lei Jin … (2019)

Cervical cancer is one of the most common cancers threatening women's health, and the persistent infection of high-risk human papillomavirus (HPV) is closely related to the pathogenesis of cervical cancer and many other cancers. The carcinogenesis is a complex process from precancerous lesion to cancer, which provides an excellent window for clinical prevention, diagnosis, and treatment. However, despite the various preventions and treatments such as HPV screening, prophylactic HPV vaccines, surgery, radiotherapy, and chemotherapy, the disease burden remains heavy worldwide. Currently, three types of prophylactic vaccines, quadrivalent HPV vaccine, bivalent HPV vaccine, and a new nonavalent HPV vaccine, are commercially available. Although these vaccines are effective in protecting against 90% of HPV infection, they provide limited benefits to eliminate pre-existing infections. Therefore, new progress has been made in the development of therapeutic vaccines. Therapeutic vaccines differ from prophylactic vaccines in that they aim to stimulate cell-mediated immunity and kill the infected cells rather than neutralizing antibodies. This review aims at systematically covering the progress, current status and future prospects of various vaccines in development for the prevention and treatment of HPV-associated lesions and cancers and laying foundations for the development of the new original vaccine.

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Author and article information

Contributors

Bing Mei: meibing008@163.com

Journal

Journal ID (nlm-ta): Virol J

Journal ID (iso-abbrev): Virol J

Title: Virology Journal

Publisher: BioMed Central (London )

ISSN (Electronic): 1743-422X

Publication date (Electronic): 27 September 2023

Publication date PMC-release: 27 September 2023

Publication date Collection: 2023

Volume: 20

Electronic Location Identifier: 217

Affiliations

Department of Laboratory Medicine, Jingzhou Hospital Affiliated to Yangtze University, ( https://ror.org/05bhmhz54) Jingzhou, 434020 China

Article

Publisher ID: 2188

DOI: 10.1186/s12985-023-02188-8

PMC ID: 10537582

PubMed ID: 37759219

SO-VID: 5b160a60-06eb-4b44-b80d-82f61754a450

License:

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

History

Date received : 2 June 2023

Date accepted : 19 September 2023

Custom metadata

ScienceOpen disciplines: Microbiology & Virology

Keywords: human papillomavirus type 16 (hpv-16),sequencing,variation,epitope prediction,selection pressure

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ScienceOpen disciplines: Microbiology & Virology

Keywords: human papillomavirus type 16 (hpv-16), sequencing, variation, epitope prediction, selection pressure

Genetic variation of E6 and E7 genes of human papillomavirus type 16 from central China

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Abstract

Background

Methods

Results

Conclusion

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Microbiology Society

Most cited references 47

Cervical cancer

Human papillomavirus and cervical cancer.

Human papillomavirus vaccine against cervical cancer: opportunity and challenge

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