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The possible impact of novel mutations in human papillomavirus 52 on the infection characteristics.

ABSTRACT: Human papillomavirus 52 (HPV52) infection is prevalent in the Chinese population, and variations in HPV52 show correlations with oncogenicity. However, no specific variation in HPV52 was reported to show relevancy to infection characteristics. In this study, we retrieved 222 isolates of E6 and L1 full-length genes from 197 Chinese women with HPV52 infection. After sequence alignment and phylogenetic tree construction, we found that 98.39 % of the collected variants belonged to the sublineage B2 and two variants displayed incongruence between the phylogenetic tree of E6 and L1. The analysis of the infection pattern showed that the presence of C6480A/T mutation in the L1 gene was associated with single infection (P=0.01) and persistent infection (P=0.047) of HPV52, while the A6516G nucleotide change was relevant to transient infection (P=0.018). Our data also indicated that variations T309C in the E6 gene and C6480T, C6600A in L1 were more commonly presented in patients with high-grade cytology (P<0.05). One HPV52 breakthrough infection after vaccination was identified, which hinted at the immune escape post-vaccination. Young coitarche age and non-condom usage were correlated to multiple infections. This study provided insight into the polymorphism of HPV52 and revealed the impact of variations in HPV52 on its infection characteristics.

SUBMITTER: Gong Y

PROVIDER: S-EPMC10210937 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature

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The possible impact of novel mutations in human papillomavirus 52 on the infection characteristics.

Gong Yingxin Y Wang Yan Y Zhou Qi Q Qu Wenjie W Chen Fang F Wang Yaping Y Mo Jiayin J Zhang Hongwei H Lin Lin L Bi Tianyi T Wang Xujie X Gu Jiashi J Sui Long L Li Yanyun Y

Microbial genomics 20230401 4

Human papillomavirus 52 (HPV52) infection is prevalent in the Chinese population, and variations in HPV52 show correlations with oncogenicity. However, no specific variation in HPV52 was reported to show relevancy to infection characteristics. In this study, we retrieved 222 isolates of E6 and L1 full-length genes from 197 Chinese women with HPV52 infection. After sequence alignment and phylogenetic tree construction, we found that 98.39 % of the collected variants belonged to the sublineage B2 ...[more]

PMID: 37103992

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Project description:Background/Objective: The incidence of oropharyngeal cancer (OPC) remains significant, with a rising prevalence of HPV-positive (HPV+) cases, underscoring the growing importance of appropriate treatment approaches for this condition. While HPV+ OPC typically exhibits a more favorable prognosis than HPV-negative (HPV-) OPC, certain HPV+ OPC patients still face adverse outcomes. This study aimed to assess the effectiveness of TORS versus traditional surgery in treating OPC patients and investigate the prognostic implications of specific variants in the HPV genome. Methods: The clinical information, including pathological features, treatments, and outcomes (death), of 135 OPC patients treated with traditional surgery from 2008 to 2018 (the non-TORS group) and 130 OPC patients treated with TORS from 2017 to 2021 (the TORS group) were obtained from Sun Yat-sen University Cancer Center (SYSUCC). A comparative analysis of 3-year overall survival (OS) was performed between these two groups. Furthermore, we conducted next-generation sequencing for the HPV16 genome of the 68 HPV+ OPC cases to characterize single-nucleotide variations (SNVs) in the HPV16 genome and evaluate its association with HPV+ OPC patient survival. Results: The comparative analysis of 3-year OS between the two groups (TORS vs. non-TORS) revealed a significant prognostic improvement in the TORS group for OPC patients with a T1-T2 classification (89.3% vs. 72.0%; p = 1.1 × 10-2), stages I-II (92.1% vs. 82.2%; p = 4.6 × 10-2), and stages III-IV (82.8% vs. 62.2%; p = 5.7 × 10-2) and for HPV- patients (85.5% vs. 33.3%; p < 1.0 × 10-6). Furthermore, three SNVs (SNV1339A>G, SNV1950A>C, and SNV4298A>G) in the HPV16 genome were identified as being associated with worse survival. These SNVs could alter protein interactions and weaken the binding affinity for MHC-II, promoting viral amplification and immune evasion. Conclusions: TORS exhibited a superior prognosis to traditional surgery in OPC patients. Additionally, identifying specific SNVs within the HPV16 genome provided potential prognostic markers for HPV+ OPC. These significant findings hold clinical relevance for treatment decision-making and prognostic assessment in patients with OPC.

Project description:Among the more than one hundred formally described human papillomavirus (HPV) types, 18 are referred to as high-risk HPV types due to their association with anogenital cancer. Despite pathogenic similarities, these types form three remotely related taxonomic groups. One of these groups is called HPV species 9 and is formed by HPV-16, the most common and best-studied type, together with HPV-31, -33, -35, -52, -58, and -67. Previous worldwide comparisons of HPV-16 samples showed about 2% nucleotide diversity between isolates, which were subsequently termed variants. The distribution of divergent variants has been found to correlate frequently with the geographic origin and the ethnicity of the infected patients and led to the concept of unique African, European, Asian, and Native American HPV-16 variants. In the current study, we address the question of whether geography and ethnicity also correlate with sequence variations found for HPV-31, -35, -52, and -58. This was done by sequencing the long control region in samples derived from Europe, Asia, and Africa, and from immigrant populations in North and South America. We observed maximal divergence between any two variants within each of these four HPV types ranging from 1.8 to 3.6% based on nucleotide exchanges and, occasionally, on insertions and deletions. Similar to the case with HPV-16, these mutations are not random but indicate a relationship between the variants in form of phylogenetic trees. An interesting example is presented by a 16-bp insert in select variants of HPV-35, which appears to have given rise to additional variants by nucleotide exchanges within the insert. All trees showed distinct phylogenetic topologies, ranging from dichotomic branching in the case of HPV-31 to star phylogenies of the other three types. No clear similarities between these types or between these types and HPV-16 exist. While variant branches in some types were specific for Europe, Africa, or East Asia, none of the four trees reflected human evolution and spread to the extent illustrated by HPV-16. One possible explanation is that the rare HPV types that we studied spread and thereby diversified more slowly than the more abundant HPV-16 and may have established much of today's variant diversity already before the worldwide spread of humans 100,000 years ago. Most variants had prototypic amino acid sequences within the E6 oncoprotein and a segment of the L1 capsid protein. Some had one, two, or three amino acid substitutions in these regions, which might indicate biological and pathogenic diversity between the variants of each HPV type.

Project description:BackgroundHuman papillomavirus (HPV) infection is the main cause of cervical cancer. Different types of HPV have varying carcinogenic capabilities, and viral load is one of the key indicators of pathogenicity. Currently, there is a lack of clinical data on HPV26. This study analyzed the clinical characteristics of patients with HPV26 single infection.MethodsExfoliated cervical cells were collected for HPV genotyping from women who attended gynecological outpatient clinics or physical examinations. The clinical characteristics of HPV26 single infections in both cross-sectional and follow-up studies were examined, and the association of viral load with HPV26 persistent infection and pathogenicity was investigated.ResultsThe HPV26 positive rate among women visiting hospitals for gynecological medical consultation or physical examination was approximately 0.09% (379/435,072). Among the HPV types tested, the detection rate of HPV26 was 0.37% (379/103,608). In the cross-sectional histopathological study of 101 patients with HPV26 single infection, 62.37% (63/101) presented lesion-free. The numbers of patients with cervical intraepithelial neoplasia (CIN) 1, CIN2, and CIN3 were 25, eight, and five, respectively. Cervical cancer was not detected in any patient. 71 patients attended follow-up examinations as well as HPV26 retesting up to two years, during which, 28.57% (6/21) of CIN1 patients have developed into high-grade lesions, and 9.61% (5/52) of lesion-free patients have progressed to CIN stage. The viral load in the CIN group was significantly higher than that in the lesion-free group (p = 0.012). Similarly, the viral load in the persistent infection group was significantly higher than that in the viral-clearance group (p < 0.001).ConclusionsThe pathogenicity of single HPV26 infections is moderate among high-risk types, warranting the inclusion of HPV26 in expanded screening for HPV. High viral load is an important factor in the persistent infection and pathogenicity of HPV26. Viral load is expected to serve as a screening risk factor for persistent infection and disease progression associated with HPV26.

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The possible impact of novel mutations in human papillomavirus 52 on the infection characteristics.

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The possible impact of novel mutations in human papillomavirus 52 on the infection characteristics.

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