HPV16 Intratypic Variants in Head and Neck Cancers: A North American Perspective
Human papillomavirus (HPV) is the major causative agent for cervical and many head and neck cancers (HNCs). HPVs randomly acquire single nucleotide polymorphisms (SNPs) that may become established via positive selection. Within an HPV type, viral isolates differing by <2% in the L1 region are ter...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-12-01
|
| Series: | Viruses |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1999-4915/15/12/2411 |
| _version_ | 1797379099567587328 |
|---|---|
| author | Steven F. Gameiro Mikhail Y. Salnikov Peter Y. F. Zeng John W. Barrett Anthony C. Nichols Joe S. Mymryk |
| author_facet | Steven F. Gameiro Mikhail Y. Salnikov Peter Y. F. Zeng John W. Barrett Anthony C. Nichols Joe S. Mymryk |
| author_sort | Steven F. Gameiro |
| collection | DOAJ |
| description | Human papillomavirus (HPV) is the major causative agent for cervical and many head and neck cancers (HNCs). HPVs randomly acquire single nucleotide polymorphisms (SNPs) that may become established via positive selection. Within an HPV type, viral isolates differing by <2% in the L1 region are termed “variants” and classified based on combinations of SNPs. Studies in cervical cancer demonstrate clear differences between HPV16 intratypic variants in terms of persistence of infection, tumor histology, cancer risk, and death. Much less is known about the frequency of HPV16 variants in HNC, and their effects on clinical outcomes. We combined HPV16 positive (HPV16<sup>+</sup>) HNC samples from a local Southwestern Ontario, Canada cohort with those from the Cancer Genome Atlas to create a larger North American cohort of 149 cases with clinical data and determined the distribution of intratypic variants and their impact on clinical outcomes. Most isolates were lineage A, sublineage A1, or A2, with roughly half exhibiting the T350G polymorphism in <i>E6</i>. Univariable analysis identified significant differences between 350T and 350G intratypic variants in clinical T, N, and O staging, as well as disease-free survival. Multivariable analysis failed to identify any clinical factor as a statistically significant covariate for disease-free survival differences between 350T and 350G. Significant differences in several measures of B-cell mediated immune response were also observed between 350T and 350G intratypic variants. We suggest that HPV genetic variation may be associated with HNC clinical characteristics and may have prognostic value. |
| first_indexed | 2024-03-08T20:17:18Z |
| format | Article |
| id | doaj.art-8cdc15fdb1154c088967c5e89ad98748 |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-03-08T20:17:18Z |
| publishDate | 2023-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-8cdc15fdb1154c088967c5e89ad987482023-12-22T14:49:22ZengMDPI AGViruses1999-49152023-12-011512241110.3390/v15122411HPV16 Intratypic Variants in Head and Neck Cancers: A North American PerspectiveSteven F. Gameiro0Mikhail Y. Salnikov1Peter Y. F. Zeng2John W. Barrett3Anthony C. Nichols4Joe S. Mymryk5Department of Microbiology and Immunology, The University of Western Ontario, London, ON N6A 3K7, CanadaDepartment of Microbiology and Immunology, The University of Western Ontario, London, ON N6A 3K7, CanadaDepartment of Pathology and Laboratory Medicine, The University of Western Ontario, London, ON N6A 5C1, CanadaDepartment of Otolaryngology, The University of Western Ontario, London, ON N6A 5W9, CanadaDepartment of Pathology and Laboratory Medicine, The University of Western Ontario, London, ON N6A 5C1, CanadaDepartment of Microbiology and Immunology, The University of Western Ontario, London, ON N6A 3K7, CanadaHuman papillomavirus (HPV) is the major causative agent for cervical and many head and neck cancers (HNCs). HPVs randomly acquire single nucleotide polymorphisms (SNPs) that may become established via positive selection. Within an HPV type, viral isolates differing by <2% in the L1 region are termed “variants” and classified based on combinations of SNPs. Studies in cervical cancer demonstrate clear differences between HPV16 intratypic variants in terms of persistence of infection, tumor histology, cancer risk, and death. Much less is known about the frequency of HPV16 variants in HNC, and their effects on clinical outcomes. We combined HPV16 positive (HPV16<sup>+</sup>) HNC samples from a local Southwestern Ontario, Canada cohort with those from the Cancer Genome Atlas to create a larger North American cohort of 149 cases with clinical data and determined the distribution of intratypic variants and their impact on clinical outcomes. Most isolates were lineage A, sublineage A1, or A2, with roughly half exhibiting the T350G polymorphism in <i>E6</i>. Univariable analysis identified significant differences between 350T and 350G intratypic variants in clinical T, N, and O staging, as well as disease-free survival. Multivariable analysis failed to identify any clinical factor as a statistically significant covariate for disease-free survival differences between 350T and 350G. Significant differences in several measures of B-cell mediated immune response were also observed between 350T and 350G intratypic variants. We suggest that HPV genetic variation may be associated with HNC clinical characteristics and may have prognostic value.https://www.mdpi.com/1999-4915/15/12/2411human papillomavirusintratypic variantsE6TCGAhead and neck squamous cell carcinoma |
| spellingShingle | Steven F. Gameiro Mikhail Y. Salnikov Peter Y. F. Zeng John W. Barrett Anthony C. Nichols Joe S. Mymryk HPV16 Intratypic Variants in Head and Neck Cancers: A North American Perspective Viruses human papillomavirus intratypic variants E6 TCGA head and neck squamous cell carcinoma |
| title | HPV16 Intratypic Variants in Head and Neck Cancers: A North American Perspective |
| title_full | HPV16 Intratypic Variants in Head and Neck Cancers: A North American Perspective |
| title_fullStr | HPV16 Intratypic Variants in Head and Neck Cancers: A North American Perspective |
| title_full_unstemmed | HPV16 Intratypic Variants in Head and Neck Cancers: A North American Perspective |
| title_short | HPV16 Intratypic Variants in Head and Neck Cancers: A North American Perspective |
| title_sort | hpv16 intratypic variants in head and neck cancers a north american perspective |
| topic | human papillomavirus intratypic variants E6 TCGA head and neck squamous cell carcinoma |
| url | https://www.mdpi.com/1999-4915/15/12/2411 |
| work_keys_str_mv | AT stevenfgameiro hpv16intratypicvariantsinheadandneckcancersanorthamericanperspective AT mikhailysalnikov hpv16intratypicvariantsinheadandneckcancersanorthamericanperspective AT peteryfzeng hpv16intratypicvariantsinheadandneckcancersanorthamericanperspective AT johnwbarrett hpv16intratypicvariantsinheadandneckcancersanorthamericanperspective AT anthonycnichols hpv16intratypicvariantsinheadandneckcancersanorthamericanperspective AT joesmymryk hpv16intratypicvariantsinheadandneckcancersanorthamericanperspective |