The prognosis of patients with human papillomavirus (HPV)‑negative cervical cancer is significantly worse than that of patients with HPV‑positive cervical cancer. Understanding the mechanisms of this is crucial for preventing disease evolution. In the present study, the GV367‑snail family transcriptional repressor 2 (SNAI2) lentiviral vector was constructed and transduced into C‑33A cells. Subsequently, the proliferation of tumor cells was detected using the Cell Counting Kit (CCK)‑8 method. Flow cytometry was used to analyze the cell cycle progression of tumor cells. The glucose consumption of tumor cells was detected using an oxidase assay, and the senescence of tumor cells was detected using beta‑galactosidase staining. The gene expression and the activity of p38 and ERK1/2 were detected using reverse transcription‑quantitative PCR and western blotting, respectively. The C‑33A‑SNAI2 cell line was successfully established. Compared with HeLa and C‑33A‑Wild cells, the proliferation and percentage of G0/G1‑phase cells in the C‑33A‑SNAI2 group were decreased, as detected by the CCK‑8 assay (100±0 vs. 239.1±58.3 vs. 39.7±20.1, P<0.01) and flow cytometry (34.0±7.1% vs. 46.2±10.6% vs. 61.3±5.3%, P<0.05). Compared with the HeLa group, the glucose consumption of the C‑33A‑Wild and C‑33A‑SNAI2 groups was significantly decreased (P<0.01). The results of beta‑galactosidase staining showed that the proportion of beta‑galactosidase‑positive cells in the C‑33A‑SNAI2 group was significantly decreased compared with the C‑33A‑Wild group (P<0.01). Upregulation of SNAI2 enhanced the increase in p21 expression, and the decrease in CDK1, urokinase plasminogen activator receptor (u‑PAR) and cyclin D1 expression in C‑33A cells compared with C‑33A‑Wild cells (P<0.05). In addition, the activities of p38, ERK1/2 and the phosphorylated (p)‑ERK1/2/p‑p38 ratio were decreased in the C‑33A‑SNAI2 group compared with the C‑33A‑Wild and HeLa groups (P<0.05). In conclusion, SNAI2 enhanced HPV‑negative cervical cancer C‑33A cell dormancy, which was characterized by G0/G1 arrest, by the downregulation of u‑PAR expression, and a decrease in the activity of the p‑ERK1/2 and p‑p38MAPK signaling pathways in vitro. Cancer recurrence and metastases are responsible for most cancer‑related deaths. Given that SNAI2 is required for enhancing HPV‑negative cervical cancer cell dormancy, regulating this process may promote cervical tumor cells to enter a continuous dormant state, which could be a potential approach for tumor therapy.

Integration of the human papillomavirus (HPV) genome into the cellular genome is a key event that leads to constitutive expression of viral oncoprotein E6/E7 and drives the progression of cervical cancer. However, HPV integration patterns differ on a case-by-case basis among related malignancies. Next-generation sequencing technologies still face challenges for interrogating HPV integration sites. In this study, utilizing Nanopore long-read sequencing, we identified 452 and 108 potential integration sites from the cervical cancer cell lines (CaSki and HeLa) and five tissue samples, respectively. Based on long Nanopore chimeric reads, we were able to analyze the methylation status of the HPV long control region (LCR), which controls oncogene E6/E7 expression, and to identify transcriptionally-active integrants among the numerous integrants. As a proof of concept, we identified an active HPV integrant in between RUNX2 and CLIC5 on chromosome 6 in the CaSki cell line, which was supported by ATAC-seq, H3K27Ac ChIP-seq, and RNA-seq analysis. Knockout of the active HPV integrant, by the CRISPR/Cas9 system, dramatically crippled cell proliferation and induced cell senescence. In conclusion, identifying transcriptionally-active HPV integrants with Nanopore sequencing can provide viable targets for gene therapy against HPV-associated cancers.

During acute respiratory infections, women may concurrently receive human papillomavirus (HPV) and respiratory vaccines, as observed during the coronavirus disease 2019 (COVID-19) pandemic in China. However, few studies have assessed the safety of such concurrent administration, which could impact HPV vaccination schedules. This study analyzes the safety and optimal sequence of concurrent HPV and COVID-19 vaccinations. For this purpose, we surveyed women with both vaccines from January to October 2023 in Fujian Province, China. During this process, we collected vaccination history and adverse event (AE) data via telephone or interviews. Participants were grouped as Before, Concurrent, or After based on their vaccination sequence. A Chi-squared test, exact Fisher tests, and logistic regression were used to analyze the incidence of AEs and factors influencing vaccine safety. Overall, 1416 eligible participants were included. Although overall AE risk with the HPV vaccine was unaffected by vaccination sequence, individual AEs varied statistically between groups, including pain at the vaccination site (p < 0.001) and prolonged menstruation duration (p = 0.003). Based on the results, the optimal sequence would be to receive the HPV vaccine after the COVID-19 vaccine (After group). This insight may guide future emergency vaccination sequences for HPV and other respiratory infectious diseases.

UNASSIGNED: The incidence of oropharyngeal cancer (OPC) is increasing. This study used bibliometric analysis and topic modeling to explore the research trends and advancements in this disease over the past 10 years, providing valuable insights to guide future investigations.
UNASSIGNED: 7,355 English articles from 2013 to 2022 were retrieved from the Web of Science Core Collection for bibliometric analysis. Topic modeling was applied to 1,681 articles from high-impact journals, followed by an assessment of topic significance ranking (TSR). Medical Subject Headings (MeSH) terms were extracted using R and Python, followed by an analysis of the terms associated with each topic and on an annual basis. Additionally, genes were extracted and the number of genes appearing each year and the newly emerged genes were counted.
UNASSIGNED: The bibliometric analysis suggested that the United States and several European countries hold pivotal positions in research. Current research is focused on refining treatments, staging and stratification. Topic modeling revealed 12 topics, emphasizing human papillomavirus (HPV) and side effect reduction. MeSH analysis revealed a growing emphasis on prognosis and quality of life. No new MeSH terms emerged after 2018, suggesting that the existing terms have covered most of the core concepts within the field of oropharyngeal cancers. Gene analysis identified TP53 and EGFR as the most extensively studied genes, with no novel genes discovered after 2019. However, CD69 and CXCL9 emerged as new genes of interest in 2019, reflecting recent research trends and directions.
UNASSIGNED: HPV-positive oropharyngeal cancer research, particularly treatment de-escalation, has gained significant attention. However, there are still challenges in diagnosis and treatment that need to be addressed. In the future, more research will focus on this issue, indicating that this field still holds potential as a research hotspot.

UNASSIGNED: Persistent HR-HPV causes cervical cancer, exhibiting geographic variance. Europe/Americas have higher HPV16/18 rates, while Asia/Africa predominantly have non-16/18 HR-HPV. This study in Fujian, Asia, explores non-16/18 HR-HPV infections, assessing their epidemiology and cervical lesion association for targeted prevention.
UNASSIGNED: A total of 101,621 women undergoing HPV screening at a hospital in Fujian Province from 2013 to 2019 were included. HPV genotyping was performed. A subset of 11,666 HPV-positive women with available histopathology results were analyzed to characterize HPV genotype distribution across cervical diagnoses.
UNASSIGNED: In 101,621 samples, 24.5% tested positive for HPV. Among these samples, 17.3% exhibited single infections, while 7.2% showed evidence of multiple infections. The predominant non-16/18 high-risk HPV types identified were HPV 52, 58, 53, 51, and 81. Single HPV infections accounted for 64.1% of all HPV-positive cases, with 71.4% of these being non-16/18 high-risk HPV infections. Age-related variations were observed in 11,666 HPV-positive patients with pathological results. Cancer patients were older. In the cancer group, HPV52 (21.8%) and HPV58 (18.6%) were the predominant types, followed by HPV33, HPV31, and HPV53. Compared to single HPV16/18 infection, non-16/18 HPV predominated in LSIL. Adjusted odds ratios (OR) for LSIL were elevated: multiple HPV16/18 (OR 2.18), multiple non-16/18 HR-HPV (OR 2.53), and multiple LR-HPV (OR 2.38). Notably, solitary HPV16/18 conferred higher odds for HSIL and cancer.
UNASSIGNED: Our large-scale analysis in Fujian Province highlights HPV 52, 58, 53, 51, and 81 as predominant non-16/18 HR-HPV types. Multiple HPV poses increased LSIL risks, while solitary HPV16/18 elevates HSIL and cancer odds. These findings stress tailored cervical cancer prevention, highlighting specific HPV impacts on lesion severity and guiding region-specific strategies for optimal screening in Asia, emphasizing ongoing surveillance in the vaccination era.

Patients with Human Papillomavirus (HPV+)-associated Laryngeal Squamous Cell Carcinoma (LSCC) exhibit dramatically improved survival relative to those with HPV-Negative (HPV-) tumors. In this study, the authors aimed to investigate the radiosensitivity of all available confirmed HPV+ and HPV-LSCC cells in vitro and in vivo.
Primary LSCC cells were generated from tumor specimens obtained from patients. Real-time PCR was performed to confirm HPV infection and the expression of HPV-related genes (E6 and E7), p53, and pRB. Clonogenic survival assays, western blotting, and flow cytometry were used to assess radiation sensitivity, apoptosis, and the expression of p53 and pRB. p53 and pRB knockout cells were generated using CRISPR/Cas9 technology.
HPV+ LSCC cells displayed enhanced radiation sensitivity compared to HPV- cells. Radiation-induced apoptosis in HPV+ LSCC cells, accompanied by increased levels of p53 and pRB. Knockout of p53 or pRB led to radiation resistance and attenuated radiation-induced apoptosis in HPV+ LSCC cells. In vivo experiments showed similar results, where knockout of p53 or pRB decreased radiosensitivity in tumor-bearing mice.
The present findings demonstrated that HPV+ LSCC cells displayed obvious inherent radiation sensitivity, corresponding to increased apoptosis following radiation exposure. Mechanism study showed that the expression of p53 and pRB in HPV+ cells are required for radiation sensitivity. These findings highlight a novel mechanism by which p53 and pRB play key roles in the radiation sensitivity of HPV+ LSCC compared to HPV-LSCC.

Human papillomavirus (HPV) type 81 has recently become one of the most common low-risk HPV types; however, literature focusing on it is limited. This study aimed to analyze the reasons for the increased detection rate of HPV81 and investigate its evolving pathogenicity. We analyzed the detection rates and trends of HPV81 in 229 061 exfoliated cervical cell samples collected from 2014 to 2023; collected samples of HPV81 single infections from two different time periods; and analyzed the allele frequencies, positive selection, viral load, persistent infection capacity, and pathogenicity of E6 and E7 genotypes. We found that the detection rate of HPV81 ranked first among the low-risk types in exfoliated cervical cells and exhibited a significantly increasing trend (p < 0.001). The frequency of the E6 prototype allele of HPV81 (n = 317) was significantly increased (p = 0.018) and demonstrated the strongest adaptive capacity. The viral load and persistent infection capacity of the E6 prototype were significantly higher than those of the mutants, thus serving as key drivers for increasing the detection rate of HPV81 and enhancing its pathogenicity. The viral load was positively correlated with persistent infection capacity and pathogenicity. Persistent infection was a crucial factor in the pathogenicity of HPV81. Successful adaptive evolution of HPV81 is accompanied by enhanced pathogenicity.

UNASSIGNED: This study aimed to investigate the knowledge, attitude, and practice (KAP) of human papillomavirus (HPV) and self-sampling among adult women.
UNASSIGNED: The cross-sectional, questionnaire-based study included adult women at Shanghai Pudong Hospital from October 14, 2022, to March 31, 2023. The questionnaire contained demographic information, knowledge, attitude and practice dimensions. Factors associated with KAP and self-sampling were identified by multivariate logistic regression.
UNASSIGNED: A total of 1843 valid questionnaires were collected. The average knowledge, attitude, and practice score was 10.09 ± 5.60, 26.76 ± 3.80, and 6.24 ± 2.20, respectively. Urban residents (estimate = 0.705, p < 0.001), suburban residents (estimate = 0.512, p < 0.001), as well as individuals with undergraduate degrees and higher (estimate = 0.535, p < 0.001), were associated with good knowledge, while individuals lacking a history of HPV infection (estimate = -0.461, p < 0.001) and married individuals (estimate = -0.185, p < 0.001) were less likely to have good knowledge. Higher knowledge scores (estimate = 0.087, p < 0.001) and individuals with undergraduate education and above (estimate = 1.570, p < 0.001) were associated with a positive attitude. Being married (estimate = 0.291, p = 0.049) was associated with good practice, whereas not engaging in sexual activity (estimate = -0.959, p < 0.001) or lacking a history of HPV infection (estimate = -0.499, p = 0.011) were associated with unfavorable practices. Minorities (OR = 2.787, p = 0.038) and individuals with multiple sexual partners (OR = 2.297 for two partners, OR = 2.767 for three or more partners, p = 0.020 and p = 0.022) were positively associated with self-sampling. However, higher knowledge (OR = 0.952, p = 0.026) and attitude scores (OR = 0.929, p = 0.015) were negatively associated with self-sampling.
UNASSIGNED: Demographic and behavioral factors significantly influenced KAP scores and self-sampling behaviors regarding HPV. Urban residency, higher education levels, positive attitudes, and minority status correlated with favorable outcomes, while factors like marriage and lack of sexual activity were associated with less favorable practices.

For practical reasons, in many studies PD-L1 expression is measured by combined positive score (CPS) from a single tumor sample. This does not reflect the heterogeneity of PD-L1 expression in head and neck squamous cell carcinoma (HNSCC). We investigated the extent and relevance of PD-L1 expression heterogeneity in HNSCC analyzing primary tumors and recurrences (LRs), as well as metastases. Tumor tissue from 200 HNSCC patients was immunohistochemically stained for PD-L1 and analyzed using image-analysis software QuPath v3.4 with multiple specimens per patient. CPS was ≥20 in 25.6% of primary tumors. Intra-tumoral heterogeneity led to a therapeutically relevant underestimation of PD-L1 expression in 28.7% of patients, when only one specimen per patient was analyzed. Inter-tumoral differences in PD-L1 expression between primary tumors and lymph node metastasis (LNM) or LR occurred in 44.4% and 61.5% (CPS) and in 40.6% and 50% of cases (TPS). Overall survival was increased in patients with CPS ≥ 1 vs. CPS < 1 in primary tumors and LNM (hazard ratio: 0.46 and 0.35; p < 0.005); CPS in LR was not prognostic. Our analysis shows clinically relevant intra- and inter-sample heterogeneity of PD-L1 expression in HNSCC. To account for heterogeneity and improve patient selection for immunotherapy, multiple sample analyses should be performed, particularly in patients with CPS/TPS < 1.

BACKGROUND: The persistent infection of high-risk Human papillomavirus(HPV) is considered the main cause of cervical intraepithelial neoplasia and cervical cancer. But various cervical lesions caused by HPV infection can be properly prevented by timely vaccination. However, the distribution of HPV genotypes varies geographically.
METHODS: Retrospective analysis of high-risk HPV prevalence of 16,150 women from 2020 to 2022 in xianning of China. HPV genotyping was performed using a PCR-RDB Kit that can detect 18 high-risk HPV genotypes recommended by China\'s National Medical Products Administration. The prevalence of 18 high-risk HPV genotypes and their relationship with cervical lesions as well as vaccine efficacy were analyzed.
RESULTS: A total of 2431 women were confirmed to have different types of high-risk HPV infections. The overall positive rate reached 15.05%(2431/16,150). The most prevalent high-risk HPV genotypes were HPV52, 16, 58, 53, and 51. The prevalence of high-risk HPV reached peak at age ≤ 20(20.95%) and age ≥ 61(20.56%). The most prevalent high-risk HPV genotypes were HPV16, 58, 18, 33 and 52 in cervical cancer cases, HPV16, 52, 58, 33 and 18 in CIN2/3 cases, and HPV52, 58, 16, 53 and 18 in CIN1 cases, respectively.
CONCLUSIONS: HPV16, 58 and 18 are the most dangerous and carcinogenic genotypes in xianning, China. Conducting epidemiological investigations on high-risk HPV has significant clinical value in guiding HPV vaccination work.