The zinc transporter SLC39A6, a member of the ZIP (Zrt-Irt-like protein) family, mediates zinc influx from the extracellular milieu into the cytosol and is indispensable for the function of numerous enzymes, transcription factors and signaling molecules. Previous studies have shown that SLC39A6 expression is associated with prognosis in esophageal squamous cell carcinoma and cervical cancer, indicating its potential impact on patient survival and tumor immunity. But a comprehensive pan-cancer analysis of SLC39A6 is still lacking. This study aimed to systematically delineate the oncogenic and prognostic relevance of SLC39A6 across multiple cancer types, to unravel its interplay with immune-infiltration patterns in the tumor micro-environment, and to preliminarily identify SLC39A6-associated therapeutic vulnerabilities. SLC39A6 expression profiles were retrieved from The Cancer Genome Atlas (TCGA) and cross-validated with GTEx, TIMER, HPA, cBioPortal, GEPIA2, STRING, KEGG, GO and other public repositories. Pan-cancer analyses were performed to characterize expression patterns, prognostic value, mutational landscape and functional networks. We further interrogated correlations between SLC39A6 and immune infiltration, tumor mutational burden (TMB), microsatellite instability (MSI) and immune-regulatory genes. Drug-sensitivity associations were evaluated using the CellMiner database, which facilitated molecular docking to predict binding poses and subsequent in vivo validation of lead compounds. SLC39A6 exhibited marked dysregulation across diverse tumor types and was significantly linked to patient survival. High SLC39A6 expression is associated with reduced overall survival and progression-free survival, particularly in cervical squamous cell carcinoma (CESC), as evidenced by studies that have analyzed the gene's expression and its impact on patient survival. Immune deconvolution revealed robust associations between SLC39A6 levels and the abundance of cytotoxic T cells, dendritic cells, macrophages and other immune subsets. CellMiner analyses demonstrated that increased levels of SLC39A6 resulted in enhanced sensitivity to the PI3Kα inhibitor CH5132799. Molecular docking studies predicted a strong affinity between CH5132799 and the zinc-binding pocket of SLC39A6, while mouse xenograft models further validated that CH5132799 effectively inhibited SLC39A6-mediated tumor growth. SLC39A6 regulates the dynamics of immune infiltration and impacts prognosis in a wide range of malignancies. It emerges as a promising biomarker for prognosis, immunology, and therapy in the field of precision oncology.

HighlightsWhat are the main findings?A three-miRNA panel (miR-21, miR-205, and miR-218) improves the detection of HSIL and cervical cancer compared to individual biomarkers.Circulating miRNA expression patterns are associated with HPV status, including HPV16/18 positivity and multiple HPV infections.What are the implications of the main findings?Circulating miRNA signatures represent a promising minimally invasive approach to refine risk stratification in cervical dysplasia.Integration of miRNA biomarkers with HPV-based screening may enhance early detection and clinical surveillance strategies.Persistent high-risk human papillomavirus (hr-HPV) infection drives cervical carcinogenesis, yet improved molecular biomarkers are needed to define high-risk groups. Circulating microRNAs (miRNAs), stable in blood and involved in carcinogenic pathways, represent promising liquid biopsy biomarkers. This study assessed five miRNAs for distinguishing high-grade squamous cell intraepithelial lesions (HSILs) and cervical cancer from healthy controls and for HPV stratification. Circulating miRNAs were quantified in blood samples from 80 women (38 HSIL, 10 cervical cancer, and 32 controls). Relative expression by disease and HPV status was measured by RT-qPCR and normalized to miRNA-23a. Diagnostic performance of single and combined miRNAs was evaluated by logistic regression and ROC curve analysis. Three circulating miRNAs (miR-21, miR-205, and miR-218) were found to be significantly differentially dysregulated in the patient cohorts. A combination of the three markers showed the best diagnostic value for HSIL (AUC of 0.81, sensitivity of 79%, and specificity of 71%) and cancer (AUC of 0.81, sensitivity of 90%, and specificity of 65%). Whereas miR-205 was significantly associated with HPV16/18 in HSIL patients, the combined model had the highest diagnostic performance for multiple HPV infections. Circulating miRNA signatures show promise as liquid biopsy biomarkers for detecting cervical dysplasia and stratifying for HPV status in HSIL, warranting validation in larger prospective studies.

Persistent high-risk human papillomavirus (hrHPV) infection is a major risk factor for high-grade squamous intraepithelial lesions (HSIL) and cervical cancer. Although HPV vaccines effectively prevent infections with vaccine-covered HPV types, they do not eliminate established infections. Additionally, not all HPV types associated with cervical cancer are covered by the vaccine. Therefore, treatment strategies for HPV-related cervical lesions remain an important clinical challenge. A systematic search was conducted in PubMed, EMBASE, Web of Science, and the Cochrane Library to identify studies evaluating the efficacy of focused ultrasound in treating HPV and cervical low-grade squamous intraepithelial lesions (LSIL). Ten eligible observational studies were included. Study quality was assessed using the MINORS criteria, and evidence quality was evaluated based on GRADE guidelines. A meta-analysis was performed using Stata 12.0 software. Focused ultrasound treatment led to HPV clearance in 74% of cases (ES = 0.74, 95% CI: 0.64-0.85, P < 0.001). Additionally, 94% of women with LSIL histology before treatment had a normal cervical biopsy at follow-up (ES = 0.94, 95% CI: 0.92-0.97, P < 0.001), and 87% of women with abnormal ThinPrep cytology (TCT) results had normal cytology at follow-up (ES = 0.87, 95% CI: 0.78-0.96, P < 0.001). Compared to the observation group, focused ultrasound treatment was significantly more effective in clearing HPV (OR = 3.58, 95% CI: 2.21-5.81, P < 0.001). Similarly, focused ultrasound was superior to interferon treatment for HPV clearance (OR = 4.22, 95% CI: 1.12-15.96, P = 0.034). The quality of evidence across studies was rated as low to moderate. This meta-analysis demonstrates that focused ultrasound achieves a 74% HPV clearance rate and 94% LSIL resolution in women with cervical LSIL and concurrent hrHPV infection. While superior to observation and interferon, the evidence remains low-to-moderate due to the observational nature and geographic concentration of included studies. Future multicenter RCTs are essential to validate these results and assess long-term outcomes, including recurrence and obstetric safety.

Cervical cancer (CC) is the third most commonly occurring cancer and the fourth most common cause of cancer-related death in women. Squamous cell carcinoma (SCC) comprises ~70% of CC cases; however, its detailed molecular mechanisms are still unclear. 24 pairs of SCC and para-tumor tissues were detected with RT-qPCR, respectively. MTT and EdU assays were performed to demonstrate the role of MYH9 in SCC cell proliferation. Transwell and Boyden were performed to demonstrate the role of MYH9 in SCC cell progression. A Western blot was performed to demonstrate the mechanism of MYH9 in SCC. The results showed that mRNA and protein levels of MYH9 were higher in SCC samples than in para-tumor samples, and MYH9 knockdown suppressed the proliferation of SCC cells, and suppressed the migration and invasion of the Siha cell line, but not the C-33A cell line. Mechanistic assays showed that knockdown of MYH9 inhibited the epithelial-mesenchymal transition (EMT) and downstream cell-cycle factors, including c-Jun and cyclin-D1. MYH9 expression was upregulated in samples with SCC. Furthermore, the in vitro assays demonstrated that MYH9 had roles in promoting the proliferation of the SCC Siha and C- 33A cell lines and inducing the migration and invasion of Siha cells via regulating EMT signals and downstream cell-cycle factors. MYH9 acts as an oncogenic gene in SCC, which promotes the carcinogenesis and progression of SCC cells via EMT signaling, and it may serve as a valuable patent for targeted treatment biomarker of SCC.

Research on the impact of tumor-infiltrating immune cells(TIICs) combined with systemic inflammatory response (SIR) factors on cervical lesions and the prognosis of squamous cell cervical cancer (SCC) is limited. Therefore, this study aimed to evaluate the predictive and prognostic significance of TIICs and SIR factors in cervical epithelial lesions, specifically non-cervical epithelial lesions (NC), high-grade squamous intraepithelial lesions (HSIL), and SCC. This retrospective study analyzed 163 patients in three cohorts: NC (n = 59), HSIL (n = 52), and SCC (n = 52). Tumor-infiltrating immune cells (TIICs) in the tumor/lesion center and adjacent stroma were assessed via immunohistochemistry and multiplex immunofluorescence, while systemic inflammatory response (SIR) factors were derived from preoperative blood counts. The primary outcome was relapse-free survival (RFS) in the SCC cohort, analyzed using Cox proportional hazards regression. TIICs were significantly elevated in the HSIL group compared with those in the NC group, accompanied by reduced platelet counts (PLT). The tumor stroma (TS) exhibited a greater degree of TIICs than the tumor/lesion center (TC) in both the HSIL and SCC groups. The presence of CD163+, CD11b+, and FOXP3 + TIICs, along with PLT levels, emerged as key indicators associated with the advanced histological stage. Compared to tTIICs, sTIICs demonstrated superior diagnostic performance in differentiating between HSIL and SCC groups. Lower levels of PLT (hazard ratio [HR] = 5.047, 95% confidence interval [CI]:1.373–18.540, P = 0.015), higher CD4 + T cells (HR = 0.211, 95%CI:0.062–0.722, P = 0.008), and FOXP3 + regulatory T cells (Tregs) (HR = 0.245, 95%CI:0.073–0.820, P = 0.010) were identified as poor prognostic indicators for recurrence-free survival (RFS) in SCC. A combination of FOXP3 + Tregs and PLT provided a more robust prediction of SCC recurrence. An increase in exhausted CD4 + T cells likely explains the observation that higher CD4 + T-cell infiltration correlated with lower RFS in SCC. The spatial distribution of TIICs, particularly the density in the tumor stroma, increases across the histological spectrum of cervical lesion severity. A signature combining FOXP3 + Treg cells and preoperative platelet counts provides a robust model for predicting SCC recurrence. Furthermore, the accumulation of exhausted CD4 + T cells appears to be a hallmark of disease advancement and poor prognosis, offering potential targets for personalized immunotherapy.

Deep learning enhanced label-free cervical screening via stimulated Raman cytology.

This study investigated the epidemiological characteristics, subtype distribution, and clinical correlations of cervical human papillomavirus (HPV) infection in Jingmen, China. A retrospective study of 5,155 women screened at Jingmen Central Hospital (2022-2024). The participants were categorized into 6 age groups: ≤ 20 years (n = 54), 21-30 years (n = 791), 31-40 years (n = 1,757), 41-50 years (n = 1,371), 51-60 years (n = 968), and ≥ 61 years (n = 214). HPV genotyping and histopathology were used to assess infection patterns and lesion correlations. The infection rates of high-risk HPV (HR-HPV), low-risk HPV (LR-HPV), and mixed infections were 18.10% (933/5,155), 3.38% (174/5,155), and 3.38% (174/5,155), respectively. HR-HPV infections exhibited a bimodal age distribution, with peak prevalence in women aged ≤ 20 years (33.33%) and ≥ 61 years (39.25%). This age-related difference was statistically significant (χ² = 81.430, p < 0.001). The dominant subtypes were HPV52 (23.5%), HPV16 (13.9%), and HPV58 (13.3%). Notably, HPV16 was significantly more prevalent in high-grade squamous intraepithelial lesions (HSIL; 44.3%) and cervical cancer (CC; 55.5%), compared with low-grade lesions (p < 0.01). This study identified both adolescent/young women (≤ 20 years) and older women (≥ 61 years) as high-risk populations for HR-HPV infection. Notably, HPV16 (55.5%) exhibited significantly higher detection rates in cervical cancer cases, emphasizing the importance of prioritizing this subtype in region-specific vaccine-based prevention strategies. These findings underscore the need for tailored clinical management approaches based on viral subtype distribution and lesion severity.

Mitochondrial dysfunction has been increasingly implicated in carcinogenesis, with alterations in mitochondrial DNA (mtDNA) copy number reported across various cancer types. However, the role of mtDNA copy number changes in the progression from cervical intraepithelial neoplasia to invasive cervical cancer remains insufficiently characterized. The present study aimed to elucidate the association between mitochondrial DNA copy number (mtCN) variations and the progression of cervical intraepithelial neoplasia (CIN) to cervical cancer, and to evaluate the potential of mtCN as a biomarker for cervical cancer risk stratification. A cohort of 100 participants from the Gynecology and Obstetrics Clinic of Ankara Etlik City Hospital (Ankara, Türkiye) was enrolled. Cervical samples from the participants were categorized into four groups as follows: Normal (n=32), low-grade squamous intraepithelial lesion (CIN1; n=21), high-grade squamous intraepithelial lesion (CIN2/3; n=23) and cervical cancer (n=8). The remaining 16 samples were excluded from the analysis due to inadequate DNA yield or quality. Quantitative PCR was employed to quantify mtCN relative to nuclear DNA. Differences in mtCN according to disease category, smoking status and human papillomavirus (HPV) status were analyzed, and logistic regression modeling was performed to identify independent predictors of high-risk cervical disease (HSIL and invasive cancer). The study revealed a statistically significant stepwise increase in mtCN concomitant with increasing disease severity, reaching the highest level in cervical cancer. Notably, HPV-positive samples exhibited elevated mtCN levels compared with HPV-negative samples. In addition, smoking was associated with a significant increase in mtCN within cervical tissues. A triple model comprising mtCN fold change, smoking status and HPV status demonstrated superior predictive performance for distinguishing high-risk cervical disease, with a sensitivity of 79% and specificity of 92%. The findings indicate that mtCN alterations are associated with the progression of CIN to cervical cancer, particularly in cases who are HPV positive and smoke. To substantiate these findings and evaluate their clinical utility, larger longitudinal studies with standardized assessment protocols are imperative. However, the present study underscores the potential of mtCN as a biomarker for cervical cancer risk assessment and highlights the necessity for continued exploration into its role in tumorigenesis and diagnostic applications.

The cGAS-STING pathway has established itself as a critical innate immune pathway that has the ability to significantly affect tumor initiation and progression. The expression, methylation, immunological functions, and prognostic importance of cGAS-STING pathway-related genes in cervical squamous cancer (CESC) patients have not yet been thoroughly elucidated. First, we explored the expression of cGAS and STING in cervical carcinoma samples from TCGA by comparing the mRNA and protein levels of cGAS and STING in both TCGA cervical tumor patient samples and cervical tumor cell lines. Second, we examined the CD4+T and CD8+T cell infiltration in STING high and low samples and made Kaplan-Meier prognosis analysis of STING protein expression. Third, to verify the findings in TCGA public datasets, we retrospectively selected 40 cervical squamous carcinoma patients and 10 normal cervical tissues and evaluated cGAS and STING protein expression using immunohistochemistry (IHC). All patients have detailed clinical information, which includes age, FIGO stage, menstruation status, follow-up time, histology, tumor diameter, and serum tumor markers. In both cervical tumor patient samples and cell lines, we observed that cGAS is increased, whereas STING is decreased in tumors, which leads to decreased CD4+T and CD8+T cell infiltration and poor prognosis. Furthermore, the cGAS mRNA transcript showed a gradual increase and STING mRNA showed a decrease according to the tumor stage, tumor grade, metastasis status, and histology types. We confirmed the expression of cGAS and STING proteins in clinical cervical tumor samples using IHC. Mechanically, cGAS and STING showed different DNA methylation patterns, which might contribute to the differences in cGAS and STING mRNA and protein levels. Our work identified different expressions and methylation patterns of cGAS and STING in cervical cancer and their correlation with immune T cell infiltration and prognosis. More mechanistic study is needed to understand the cGAS-STING pathway in cervical squamous tumor.

Background: Small-cell neuroendocrine carcinoma (SCNEC) of the cervix is a rare malignancy with aggressive behaviour and poor prognosis, comprising < 2% of cervical cancers [1-3]. They are more frequent in India compared to western countries, and in younger age groups. Case: We report a 33-year-old woman who underwent hysterectomy for presumed fibroid uterus. Postoperative histopathology revealed high-grade SCNEC, FIGO Stage IB2, with margin positivity and lymphovascular space invasion (LVSI). Immunohistochemistry confirmed neuroendocrine differentiation. Multidisciplinary tumour board consensus was for adjuvant chemoradiation with weekly cisplatin. In view of paucity of guidelines, patient received radiotherapy as per guidelines for Squamous cell carcinoma cervix. Conclusion: SCNEC is a rare presentation in cervix with non-specific symptoms and imaging findings. A high clinical suspicion and immunohistochemistry are pivotal for diagnosis. SCNEC have early hematogenous spread, high recurrence rates, and poor survival outcomes compared with squamous and adenocarcinoma cervical cancers, and hence early diagnosis and aggressive multimodal treatment are of paramount importance.

Persistent infections with high-risk human papillomavirus (HR-HPV) are the primary cause of vaginal/cervical squamous intraepithelial neoplasia (VAIN/CIN) and cervical cancer (CC), with the prevalence of infection escalating alongside disease severity. Notably, the α-9 HPV species was responsible for 58.20% of all HR-HPV infections in our study. Given the absence of therapies to eradicate established infections, developing effective therapeutic vaccines is a critical priority. The HPV E6 oncoprotein represents an ideal target for such immunotherapies. In this study, we used a comprehensive in silico approach to identify and characterize potential T-lymphocyte epitopes from the E6 proteins of α-9 HR-HPV, which was predominant in our study cohort. Our integrated bioinformatics pipeline encompassed sequence analysis for conservation, followed by rigorous prediction of antigenicity, allergenicity, proteasomal processing, TAP transport efficiency, and immunogenicity. Through this systematic screening, we identified a panel of epitope candidates predicted to have a high potential for eliciting a robust and specific immune response. While these predictions provide a powerful theoretical foundation, it must be stressed that they constitute computational hypotheses requiring mandatory experimental validation. Our findings do not constitute functional epitopes but rather offer a prioritized, evidence-based roadmap for future laboratory investigations. This work significantly accelerates the rational design of HPV therapeutic vaccines by narrowing the focus to the most viable candidates, thereby conserving substantial time and resources in the downstream experimental verification process.

This study aimed to characterize disturbances in vaginal microbiota among patients with squamous intraepithelial lesions (SIL) or cervical cancer (CC), and to identify specific bacterial genera with potential as diagnostic or prognostic biomarkers. We also explored microbiota of peritoneal fluid in CC patients across different pathological subtypes. A total of 76 participants were enrolled, including 44 SIL and 32 CC patients, further classified into four groups: low-grade SIL (LSIL; n = 14), high-grade SIL (HSIL; n = 30), squamous cell carcinoma (SCC; n = 18) and adenocarcinoma (ADC; n = 14). Vaginal secretions were collected from all participants, and free peritoneal fluid was obtained from 16 SCC and 12 ADC patients. Vaginal HPV status was monitored semiannually over two years in 25 HSIL patients. Microbial composition was analyzed using 16S rRNA gene sequencing. Vaginal bacterial abundance was significantly higher in the CC group than in the SIL group. A non-significant decrease in Lactobacillus abundance (SIL: 60.89% vs. CC: 52.37%; p = 0.247) and an increase in anaerobic bacteria including Prevotella (SIL: 0.14% vs. CC: 0.79%; p < 0.001) and Sneathia (SIL: 0.21% vs. CC: 1.57%; p = 0.097) were observed in CC patients. Lactobacillus abundance was negatively correlated with these anaerobic genera. Among HSIL patients, those who cleared HPV infection had a significantly higher abundance of Atopobium (5.25% vs. 0.65%; p = 0.022). Furthermore, ADC patients showed significantly higher microbial abundance in both vaginal and peritoneal fluid samples compared to SCC patients. LEfSe analysis indicated that Prevotella was the most distinguishing genus in the ADC group. Our study suggests that vaginal microbiota diversity may be associated with the severity of cervical lesions. Additionally, ADC patients showed heightened microbial diversity in both vaginal and peritoneal fluid microbiota compared to SCC patients.

Using a retrospective cohort of 21,282 individuals aged 10–89 years (634 males, 20,648 females) from Jilin Province between October 2017 and September 2019, we performed HPV genotyping and colposcopy-directed biopsy to delineate age- and genotype-specific infection patterns. High-risk HPV prevalence peaked in adolescence (≤ 18 years) and declined thereafter, whereas low-risk types showed modest age trends (P < 0.001); women had higher rates than men at every age (P < 0.001). HPV16, 18, 33 and 58 were strongly linked to high-grade squamous intraepithelial lesions or cervical cancer, with adjusted ORs (Model II) of 2.41, 0.53, 2.32 and 1.72, respectively. A U-shaped, nonlinear age relationship emerged, with infection risk threshold ages (fold K) at 26, 42, 30 and 37 years. These findings indicate that HPV vaccination and screening should prioritize women ≤ 26 years and re-engage those > 37 years.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12985-025-02963-9.

Human papillomavirus (HPV) infection presents neoplastic risks in both cervix and anus. High-resolution colposcopy/anoscopy is crucial for assessing these regions but has suboptimal accuracy. This study aims to develop a Convolutional Neural Network (CNN) to identify and differentiate low-grade (LSIL) and high grade (HSIL) squamous intraepithelial lesions, in the cervix and anus. A retrospective multicenter study was conducted to develop a CNN using 320 colposcopy and anoscopy examinations, from 3 device types. Dataset included 88,073 frames, categorized as LSIL or HSIL based on pathological analysis. The data was split into training/validation (90%, n = 79,265, including a threefold cross-validation) and test sets (10%, n = 8808). Diagnostic metrics including sensitivity, specificity, accuracy, positive and negative predictive values (PPV and NPV, respectively) and an area under the receiving operating and the precision-recall curves (AUC-ROC and AUC-PR) were calculated. During training/validation phase, the model achieved an average sensitivity for HSIL of 98.1% (IC95% 97.6–98.5%), specificity of 97.4% (IC95% 96.0–98.8%), PPV of 97.2% (IC95% 95.8–98.7%), NPV of 98.2% (IC95% 97.7–98.6%), and accuracy of 97.7% (IC95% 97.2–98.6%). The mean AUC-ROC and AUC-PR were both 0.98 ± 0.01. In the testing phase, performance metrics for HSIL were: sensitivity 99.0%, specificity 97.8%, PPV 97.6%, NPV 99.0%, and accuracy 98.3%. HPV infection impacts both cervical and anal region. This study developed a pioneering CNN to differentiate HSIL and LSIL in HPV-related dysplastic lesions, during cervical and anal examinations. This model achieved promising results, suggesting its potential to improve detection accuracy and cost-effectiveness in clinical practice.

To explore the somatic and immunologic landscape of cervical primary versus metastatic tumors for differential sensitivity of metastatic cervical sites and potential therapeutic implications. Patients with sequenced squamous cell cervical cancer were selected from the Tempus Database (2016-2023). The cohort included 136 unmatched samples (73 primary, 63 metastatic sites). Pathogenic somatic mutations and gene expression patterns of immune cells were evaluated for relative intratumor abundance. Immune cell percentages, tumor mutational burden, and tumor neoantigen burden (tumor mutational burden) were compared across tumor sites. χ2/Fisher exact tests or Kruskal-Wallis tests were used to assess statistical significance. The median cohort age was 52 years (interquartile range; 42-60). High tumor mutational burden (≥ 10 mut/Mb) was seen in 9.6% (9% primary, 0% lung, 17% liver, 17% lymph node, p = .7) of patients. High microsatellite instability (MSI) was noted in 1.5% (p = .7) of patients. PD-L1 status was positive in 78% (76% primary, 88% lung, 71% liver, and 80% lymph node, p = .8) of patients. Median tumor neoantigen burden was 1.71 (interquartile range; 0.98-3.20). Liver lesions had the lowest percentage of B cells (p = .001) and a higher percentage of macrophages (p = .053) compared with other sites. There was a trend toward lower percentages of CD4 cells (p = .053) and natural killer cells (p = .090) in lymph nodes compared with other sites. PIK3CA was the most common pathogenic somatic alteration but not statistically different across sites (q = 0.9). Molecular and immune profiling of primary and metastatic lesions indicated that liver lesions had a less immunogenic microenvironment. Further interrogation of the molecular landscape across paired samples is needed to better inform the development and use of novel therapies.

Cervical cancer, a leading cancer among women, is strongly associated with Human Papillomavirus infection, but host genetic factors also contribute to the progression from high-grade squamous intraepithelial lesions (HSIL) to invasive cancer. Interleukin-10 (IL-10), an immunosuppressive cytokine, may influence susceptibility to HSIL and cervical cancer through genetic variations. This study aimed to compare IL-10 gene promoter polymorphisms, -1082 A > G and − 819T > C, in women diagnosed with HSIL or cervical cancer and those with negative for intraepithelial lesion or malignancy (NILM). In this case-control study, 309 women were analyzed, including 142 with HSIL or cervical cancer and 167 controls with NILM. Blood samples were collected for DNA extraction and genotyping of polymorphisms through PCR amplification. Statistical analyses included comparisons of genotype and allele frequencies, haplotype frequency, and assessments of Hardy-Weinberg equilibrium and linkage disequilibrium. The mean age was 33.4 years for cases and 41.7 years for controls (p < 0.05). For the − 1082 A > G polymorphism, the GG genotype was significantly associated with a decreased risk of HSIL and cervical cancer (p = 0.0266, OR = 0.35). Recessive model (GG vs. AA + AG) confirmed this association (p = 0.0045, OR = 0.29). AC/GC diplotype was associated with a 2-fold increased risk of cervical lesions. Further studies are needed to confirm our results.

BackgroundTo study the prevalence of HPV in Sanming, China before conducting large-scale HPV vaccination is important to guide public health preventive measures and maximize the effectiveness of vaccination.ObjectiveProvide an overall understanding of the prevalence of HPV in Sanming to help guide HPV screening and vaccine selection in the future.MethodsA retrospective analysis of 11,886 female patients who underwent cervical screening was performed. We analyzed the overall HPV prevalence in the region, the prevalence based on each age group and different genotypes and the distribution of HPV with different pathological diagnoses.ResultsThe overall HPV prevalence was 17.85%, with peak positivity in the ≤ 20-year group (42.24%) and secondary elevation in 61-70-year-olds (31.90%). HPV52 (23.37%), HPV58 (14.00%), and HPV16 (11.40%) constituted the dominant genotypes. Among 2,122 HPV-positive patients, pathological diagnoses included: chronic cervicitis (83.22%, 1,766/2,122; predominantly HPV52 [22.88%]), low-grade squamous intraepithelial lesions (LSIL, 11.50%, 244/2,122; HPV52 [29.92%]), high-grade SIL (HSIL, 3.49%, 74/2,122; HPV16 [40.54%]), and cervical cancer (1.79%, 38/2,122; HPV16 [52.63%]). Notably, HPV16 prevalence increased significantly with lesion severity.ConclusionThis study found that the overall HPV infection rate in Sanming, China, was slightly higher than in other regions of the country, and the main prevalent genotypes were HPV52 and HPV58. In order to maximize patient benefit, vaccine selection should ideally cover other common genotypes in the region, in addition to HPV16 and HPV18.

Squamous cervical cancers generally arise as a result of persistent infection with high-risk human papillomaviruses (hrHPVs) and occur near the squamocolumnar junction (SCJ) and within the transformation zone (TZ). The susceptibility of the TZ to HPV-related carcinogenesis appears linked to epithelial cell plasticity, with squamous metaplasia originating from a specialized stem cell population at this site. Two alternative cell populations have been implicated: keratin (K)7+ve cuboidal cells located at the SCJ vs a more broadly distributed K17+ve cervical reserve cell population. To distinguish between the hypotheses, we utilized multiplex immunofluorescence and large-scale digital imaging to map cell populations at the TZ of 165 women with and without hrHPV infections. Our results did not reveal a distinct population of K7+ cuboidal cells at the SCJ but found instead that the cuboidal and columnar cells of the TZ express K7 and K8 throughout and lack the p63 transcription factor required for epithelial stratification. Squamous metaplasia and reserve cells, which are defined by their subcolumnar location and pattern of biomarker expression (K5/K17/P63), were conspicuous at cervical crypt entrances within the TZ extending proximally toward the endocervix. In HPV-infected tissue, crypt-entrance regions with thin high-grade squamous intraepithelial lesion pathology showed prominent expression of hrHPV E6/E7 mRNA, as detected by fluorescence in situ hybridization, and p16/MCM expression, with infection also apparent in neighboring reserve cells. In some instances, normal/uninfected reserve cells (E6/E7 mRNA-ve) and squamous metaplasia were not only seen close to these regions of hrHPV infection but also extended well beyond the infected area both laterally and by depth. Our results confirm that the reserve cells underneath the columnar epithelia at TZ have the potential to undergo malignant squamous transformation via reserve cell proliferation, in agreement with previous histopathological studies. These translational findings highlight the importance of understanding the molecular biology of the epithelial sites where HPV cancers develop and suggest that in high-risk individuals, treatment strategies should target a wider area than previously thought.

Objective: This study aims to explore the benefit of adjuvant chemoradiotherapy compared with radiotherapy alone following a radical hysterectomy with pelvic lymphadenectomy. The study focuses on patients with clinically early-stage squamous cervical cancer who have a single high-risk factor postoperatively. Methods: This retrospective study included women diagnosed between 2001 and 2018, with: (1) clinical tumour (cT) stage 1A2-2A2, (2) cervical squamous carcinoma, (3) treated with radical hysterectomy and pelvic lymphadenectomy (4) followed by adjuvant (chemo)radiotherapy, and with (5) one high-risk factor (i.e., positive resection margins, parametrial involvement, or pelvic lymph node metastases). Recurrence-free and overall survival were estimated using Kaplan-Meier and Cox proportional hazards analyses. Inverse probability treatment weighting was used to adjust for confounding. Results: Of the 122 patients with squamous cell carcinoma and one high-risk factor, 76 (62%) received adjuvant chemoradiotherapy and 46 (38%) received adjuvant radiotherapy alone. Larger tumour size, tumour grade 3, and pathological parametrial invasion were more common in the radiotherapy group, while patients who received chemoradiotherapy were more likely to have multiple lymph node metastases. The unadjusted and for confounding adjusted 5-year survival rates were comparable between the adjuvant chemoradiotherapy and radiotherapy groups for both recurrence-free survival (85% versus 87%; p = 0.58, and 84% versus 91%; p = 0.49) and overall survival (84% versus 87%; p = 0.51, and 84% versus 91%; p = 0.49). Conclusions: Adding chemotherapy to radiotherapy may not improve survival of patients with early squamous cervical cancer treated with radical hysterectomy and pelvic lymphadenectomy, and with a single postoperative high-risk factor.

e17502 Background: Checkpoint inhibitors (ICIs) has been approved for treating multiple solid tumors, the real-world clinical benefits are under widely discussion. In addition, as more patients failed previous ICIs, the following treatment strategies and effectiveness warrant investigation. Cadonilimab (AK104) is a PD-1/CTLA-4 bispecific antibody, which is expected to exert enhanced anti-tumor activity or reverse immunotherapy resistance after single target ICI. This study focused on the real-world efficacy and safety of cadonilimab in R/M solid tumors, first reported performance of cadonilimab in R/M head and neck squamous cell carcinoma (HNSCC), enriched performance of cadonilimab in R/M cervical cancer (CC), and also summarized the effectiveness of re-treatment with cadonilimab for patients failed previous ICIs. Methods: We reviewed histologically confirmed CC and HNSCC in our center. Those with R/M disease and received ≥ one cycle of cadonilimab were enrolled. Patients received cadonilimab (10mg/kg, Q3W) mono- or combination therapy. The primary endpoints were ORR and PFS (RECIST1.1). Secondary endpoints included DCR, OS, and AE (CTCAE 5.0). Results: As of December 15, 2024, a total of 36 patients (median age: 57 years) were enrolled, including 29 CC and 7 HNSCC patients. The median follow-up time was 12.1 months (9.9-14.3 months). Patients with CC were treated with cadonilimab monotherapy or combined with chemotherapy ± radiotherapy or ± anti-angiogenic therapies. The ORR were 100% (7/7), 60% (9/15), 28.6%(2/7) for 1 st , 2 nd and ≥ 3 rd line therapy, the mPFS were not reached, 6.2 months (95% CI[3.3 9.0] ), and 4.8 months (95% CI[0.3 9.4]), respectively. The mOS was not mature. Patients with HNSCC received cadonilimab plus anti-EGFR therapy (one 1 st line, five 2 nd line, one ≥3 rd line). The overall ORR, DCR and mPFS are 71.4% (5/7), 85.7% (6/7) and 8.0 months (95%CI[3.2-12.9]). The ORR and DCR of 2 nd line treatment were 80% (4/5), mPFS was 8.0 months (95CI[3.954-12.113]). mOS was not mature. Of the 11 patients who received cadonilimab for immunotherapy rechallenging, three achieved PR and six maintained SD, with ORR of 27.3% (3/11), DCR of 81.8%(9/11), and mPFS was 4.7 months (95%CI[0-10.3]). Of all patients, 19.4%(7/36) developed grade 3 AE(4 leukopenia, 1 anemia, 2 rash, and 1 pancreatitis). Conclusions: This real-world study first reported performance of cadonilimab (combined with anti-EGFR therapy) in R/M HNSCC, showing excellent ORR and PFS. In R/M CC, the combination regimen of cadonilimab based on clinical practice improved ORR (COMPASSION-16, ORR 82.9%; COMPASSION-03, ORR 32.3%). The overall safety is manageable. Furthermore, cadonilimab showed promising anti-tumor efficacy and potential to reverse resistance of single target ICI. Analysis with more samples and cancer types will continue.