S-like particles [49]. The analysis of the L1 gene is of immense importance Title Loaded From File because of its high diagnostic value [16], as the range of intratypic variations observed in this region allows the distinction and assessment of known or novel HPV types [7,50]. In the L1 coding region, one A to G transition at nt5503 and four C to G transversions were found. These five variations were also observed in a study by Arias-Pulido et al. [25] in the UnitedStates. Furthermore, the four guanine variations aare represented in the HPV-18 prototype sequence (AY262282), indicating that these variations are wide-spread. In addition, we also found a novel G to A transition at nt6906. All five sequence variations near Cterminus described above result in AA changes which may affect immune responses to HPV-18 capsid protein [25,47]. The HPV L1 model postulates that the L1 C-terminal domain is exposed on 23727046 the viral surface and expected to be highly antigenic [51]. Like L1, the L2 protein plays an important role in the initial steps of papillomavirus infection [52]. We found two sequence variations in the L2 ORF that did not result in AA changes. These changes could reflect the extreme rarity of the reference sequence that was originally obtained from a subject in southwest China. Interestingly, no sequence variation was found in E4 and E5, in contrast to a report by Arias-Pulido et al. [25] in the United States, in which there were seven sequence variations found in E4. This discrepancy may be attributed to differences in sample size as well as the geographic and racial characteristics of the study populations.ConclusionsIn summary, this study reports sequence variations in the E1, E2, E6, E7, L1 and L2 genes of HPV-18 isolates from southwest China. The sequence variations in the genes examined may contribute to HPV oncogenesis. Our data will provide a solid foundation for further biological and clinical studies, and may also be employed in epidemiological studies where sequence variations are used as markers for monitoring HPV infections in target populations. Elucidating the functional and pathological differences between intratypic variants of HPV, as well as determining the molecular basis for their propensity to induce different histological types of cervical cancer, are important areas of future investigation. Further studies of HPV sequence variation will also need to include different geographic regions with distinct and isolated human populations.AcknowledgmentsWe thank the Cancer Hospital of Sichuan Province and the 4th People’s Hospital of Chongqing for providing specimens.Author ContributionsConceived and designed the experiments: MS XD. Performed the experiments: MS TL. Analyzed the data: MS GC. Contributed reagents/materials/analysis tools: XZ.
Head and neck squamous cell carcinoma, including cancers of oral cavity, oropharynx, larynx, and hypopharynx, represents the sixth most frequent solid cancer around the world [1]. Tongue squamous cell carcinoma (TSCC) is the most common type of oral cancer and is well-known for its high rate of proliferation and nodal metastasis [2]. Although TSCC is visibly located in the oral cavity, in previous studies up to 50 of patients were already in advanced stage III and IV on presentation [3,4]. Understanding the molecular pathways of TSCC carcinogenesis and progression would be helpful in improving diagnosis, therapy, and prevention of this disease. MicroRNAs (miRNAs) are endogenously expressed small Title Loaded From File noncoding RN.S-like particles [49]. The analysis of the L1 gene is of immense importance because of its high diagnostic value [16], as the range of intratypic variations observed in this region allows the distinction and assessment of known or novel HPV types [7,50]. In the L1 coding region, one A to G transition at nt5503 and four C to G transversions were found. These five variations were also observed in a study by Arias-Pulido et al. [25] in the UnitedStates. Furthermore, the four guanine variations aare represented in the HPV-18 prototype sequence (AY262282), indicating that these variations are wide-spread. In addition, we also found a novel G to A transition at nt6906. All five sequence variations near Cterminus described above result in AA changes which may affect immune responses to HPV-18 capsid protein [25,47]. The HPV L1 model postulates that the L1 C-terminal domain is exposed on 23727046 the viral surface and expected to be highly antigenic [51]. Like L1, the L2 protein plays an important role in the initial steps of papillomavirus infection [52]. We found two sequence variations in the L2 ORF that did not result in AA changes. These changes could reflect the extreme rarity of the reference sequence that was originally obtained from a subject in southwest China. Interestingly, no sequence variation was found in E4 and E5, in contrast to a report by Arias-Pulido et al. [25] in the United States, in which there were seven sequence variations found in E4. This discrepancy may be attributed to differences in sample size as well as the geographic and racial characteristics of the study populations.ConclusionsIn summary, this study reports sequence variations in the E1, E2, E6, E7, L1 and L2 genes of HPV-18 isolates from southwest China. The sequence variations in the genes examined may contribute to HPV oncogenesis. Our data will provide a solid foundation for further biological and clinical studies, and may also be employed in epidemiological studies where sequence variations are used as markers for monitoring HPV infections in target populations. Elucidating the functional and pathological differences between intratypic variants of HPV, as well as determining the molecular basis for their propensity to induce different histological types of cervical cancer, are important areas of future investigation. Further studies of HPV sequence variation will also need to include different geographic regions with distinct and isolated human populations.AcknowledgmentsWe thank the Cancer Hospital of Sichuan Province and the 4th People’s Hospital of Chongqing for providing specimens.Author ContributionsConceived and designed the experiments: MS XD. Performed the experiments: MS TL. Analyzed the data: MS GC. Contributed reagents/materials/analysis tools: XZ.
Head and neck squamous cell carcinoma, including cancers of oral cavity, oropharynx, larynx, and hypopharynx, represents the sixth most frequent solid cancer around the world [1]. Tongue squamous cell carcinoma (TSCC) is the most common type of oral cancer and is well-known for its high rate of proliferation and nodal metastasis [2]. Although TSCC is visibly located in the oral cavity, in previous studies up to 50 of patients were already in advanced stage III and IV on presentation [3,4]. Understanding the molecular pathways of TSCC carcinogenesis and progression would be helpful in improving diagnosis, therapy, and prevention of this disease. MicroRNAs (miRNAs) are endogenously expressed small noncoding RN.
