Search Results (326)

Background: HPV genotype-based stratification estimates cervical disease risk but does not directly measure cellular transformation. We assessed whether p16 and Ki-67 improve prediction of CIN2+ beyond HPV genotype and age in a biopsy-confirmed referral cohort. Methods: This retrospective study included 531 high-risk HPV-positive women evaluated between December 2023 and January 2026 who had either margin-negative excisional histopathology or completed 12-month surveillance after conservative management. HPV genotypes were grouped as HPV16, HPV18, or other high-risk types. Independent associations were examined using prespecified multivariable logistic models; discrimination, calibration, 2000-resample bootstrap validation, and a uniform index-biopsy-reference sensitivity analysis were evaluated. Results: CIN2+ was confirmed in 191/531 women (36.0%). HPV16 positivity (adjusted odds ratio [aOR] 1.72, 95% confidence interval [CI] 1.15–2.57), age (aOR 1.027 per year, 95% CI 1.011–1.043), and p16 positivity (aOR 2.97, 95% CI 1.81–4.89) independently predicted CIN2+, whereas Ki-67 did not (aOR 1.74, 95% CI 0.90–3.35; p = 0.098). Adding p16 to age and genotype increased the AUC from 0.608 to 0.704 (ΔAUC 0.097, bootstrap 95% CI 0.057–0.138); Ki-67 increased it only to 0.707 (ΔAUC 0.003, 95% CI −0.002 to 0.015). Optimism-corrected AUCs were 0.599, 0.696, and 0.697, respectively. The uniform biopsy-reference analysis produced the same pattern. Conclusions: p16 provides reproducible incremental risk information beyond age and HPV genotype in biopsy-confirmed cervical disease, whereas Ki-67 adds little once p16 is known. Neither biomarker should replace histopathology-guided management. Full article

Background/Objectives: Anal squamous cell carcinoma (SCCA) is a rare Human Papillomavirus (HPV)-related disease in the general population but its incidence is increasing among high-risk populations, i.e., men who have sex with men (MSM), HIV+ patients and women with a history of cervical/vulvar dysplasia. The objectives of this study were: (i) to investigate the prevalence of high-risk (HR) and low-risk (LR) anal HPV infections in a high-risk cohort; (ii) to correlate specific HPV genotypes with cytological and histological outcomes; and (iii) to assess the impact of cumulative HPV genotype burden. Methods: A retrospective study (2017–2022) was conducted on 550 high-risk patients. All patients underwent anal Pap tests (ThinPrep, Hologic) and HPV genotyping (Anyplex II HPV 28, Seegene), according to our screening protocol. High-Resolution Anoscopy (HRA) was performed on 430 patients; biopsy was performed in all cases with suspicious lesions. Results: The overall HR-HPV prevalence was 57.3%. Men showed a significantly higher prevalence of HR-HPV (59.9% vs. 47.4%) and cytological abnormalities (35.8% vs. 20.2%) compared to women. Notably, HPV 16, 58 and 45 accounted for 79% of AIN2+ (Anal Intraepithelial Neoplasia of grade 2 or higher) lesions. A significant cumulative HPV genotype burden effect, i.e., the number of HPV genotypes detected, was observed: patients with ≥3 HR-HPV types showed an increased risk of AIN2+ lesions (aOR 34.72; 95% CI 4.07–296.10) and AIN1+ lesions (aOR 16.26; 95% CI 4.54–58.30) respectively. The presence of ≥3 LR-HPV genotypes in HR-HPV-positive patients is associated with an increased risk of AIN1 lesions. Conclusions: HPV 16, 58 and 45 positivity and the cumulative HPV genotype burden could represent new potential indicators for risk stratification in high-risk populations. Future larger-scale prospective studies are needed to validate these preliminary results. Full article

Background/Objectives: Angiogenesis plays a central role in the progression of cervical intraepithelial neoplasia (CIN) to cervical cancer (CC). Transvaginal Doppler ultrasonography (TVDUSG) offers a non-invasive means of assessing hemodynamic changes associated with neoplastic transformation. This study aimed to evaluate the diagnostic performance of uterine artery (UA) Doppler parameters across the full cervical disease spectrum and their associations with adverse prognostic features and clinicopathological features in CC. Methods: This prospective observational cohort study enrolled 170 patients who were divided into four groups: controls, CIN 1, CIN 2–3, and CC. All underwent TVDUSG prior to treatment. Pulsatility index (PI), resistance index (RI), peak systolic velocity (PS), end-diastolic velocity (ED), PS/ED ratio, ED/PS ratio, and time-averaged maximum velocity were recorded. ROC curve analysis was performed to assess diagnostic performance. Results: PI and RI increased progressively from controls to CC, while ED declined across groups (all p < 0.001). In patients with CC, PI correlated with tumor volume and was elevated in those with advanced-stage, parametrial and lymph node involvement (all p < 0.001). ROC analysis revealed strong diagnostic performance for PI in distinguishing CC from controls (AUC = 0.861, sensitivity 80.0%, specificity 80.4%); however, PI showed limited ability to distinguish cervical cancer specifically from high-grade CIN (AUC = 0.593). Conclusions: UA Doppler parameters, particularly PI, are associated with cervical neoplastic severity and adverse prognostic features in CC. TVDUSG may serve as a practical, non-invasive adjunct in the preoperative evaluation of cervical neoplasia, especially where advanced imaging is unavailable. Full article

Background: Large loop excision of the transformation zone (LLETZ) is an established surgical procedure for cervical intraepithelial neoplasia; however, secondary postoperative bleeding may lead to unplanned outpatient visits, hospitalization, or surgical intervention. This study aimed to evaluate the incidence and risk factors of postoperative bleeding after LLETZ. Methods: We conducted a retrospective single-center cohort study comprising 1493 patients who underwent LLETZ for the treatment of cervical dysplasia between January 2008 and May 2023 at the Medical University of Vienna. Postoperative bleeding was defined as an unscheduled outpatient presentation for bleeding from the operative site within eight weeks after LLETZ requiring additional treatment. Clinical, surgical and histopathological parameters were analyzed. Univariable logistic regression was performed to identify factors associated with postoperative bleeding, with additional stratified analyses according to the use of intraoperative cervical infiltration. Results: Postoperative bleeding occurred in 56 patients (3.8%). The median time to bleeding was 13.5 days (IQR 9.0–17.0). Among patients with postoperative bleeding, 20 (35.7%) required hospitalization, 10 (50.0%) underwent operative intervention, and 2 (10.0%) required blood transfusion. In logistic regression, increasing cone length was associated with higher odds of postoperative bleeding (OR 1.83 per cm, 95% CI 1.06–3.18, p = 0.031). Anticoagulation and/or antiplatelet therapy was also associated with an increased bleeding risk (OR 3.61, 95% CI 1.46–8.96, p = 0.006). Higher BMI was associated with lower odds of postoperative bleeding (BMI per +5 kg/m²: OR 0.62, 95% CI 0.43–0.90, p = 0.011). Conclusions: LLETZ is associated with a low risk of clinically relevant postoperative bleeding, with an unplanned outpatient re-presentation rate of 3.8% and a re-operation rate of 0.7%. Increased cone length and anticoagulation and/or antiplatelet therapy were associated with higher bleeding rates. Larger prospective studies are needed to validate these findings and improve individualized perioperative risk assessment. Full article

Background/Objectives: Human papillomavirus (HPV) testing is widely used in cervical cancer screening because of its high sensitivity, although its limited specificity requires effective triage strategies. This study aimed to evaluate the association between relative viral load (RVL) and cervical lesion severity, focusing on HPV-positive women with non-high-grade cytology. Methods: The study included 997 women with histological outcomes from a cohort of 2765 HPV-positive individuals identified among 37,030 women screened in the Bari metropolitan area (Italy) using a real-time HPV-DNA test. Associations between RVL, estimated using the ΔCt method, and lesion severity were assessed using histological and cytological classifications. Logistic regression models evaluated the independent effect of RVL, adjusting for age and HPV detection channel. Results: Lower ΔCt values (indicating higher RVL) were significantly associated with high-grade lesions (CIN2+) (OR = 0.91, 95% CI: 0.89–0.94, p < 0.001). The association was observed for HPV16 and the pooled 12-high-risk HPV detection channel, while no significant association was observed for HPV18. A similar association was observed when cytological classification was used as the outcome. Age showed a modest effect, with reduced odds of high-grade lesions observed in women aged ≥50 years. Among women with non-high-grade cytology who subsequently underwent histological assessment, 17.6% had underlying CIN2+, and RVL remained significantly associated with lesion severity in this subgroup. However, ΔCt showed only modest discrimination for high-grade lesions [AUC = 0.643 (95% CI: 0.605–0.681)]. Conclusions: Higher HPV RVL is associated with increased lesion severity, particularly for HPV16 and the pooled 12-high-risk detection channel, but not for HPV18. Given its modest standalone discriminatory performance and the selected nature of the histologically verified cohort, ΔCt should be considered an exploratory marker rather than a validated triage tool. Prospective validation is required to determine whether it provides incremental clinical value. Full article

Background/Objectives: Human papillomavirus (HPV) infection is the principal etiological factor in cervical cancer and its precursor lesions. Although vulvar condyloma is typically associated with low-risk HPV types, high-risk HPV genotypes may coexist. This study evaluated the association between vulvar condyloma, cervical cytological abnormalities, high-risk HPV positivity, and cervical histopathological outcomes. Methods: This retrospective observational study included 407 women evaluated at the Department of Obstetrics and Gynecology, Izmir City Hospital, between January 2025 and January 2026. Patients underwent cervical cytology, HPV testing, vulvar examination, and colposcopic biopsy when clinically indicated. Patients were categorized according to the presence or absence of histopathologically confirmed vulvar condyloma. Logistic regression analyses were performed to identify factors associated with vulvar condyloma. Results: Vulvar condyloma was identified in 180 patients (44.2%). Abnormal cervical cytology was recorded in 66/180 patients (36.7%) with vulvar condyloma and 41/227 patients (18.1%) without condyloma (p < 0.001). High-risk HPV positivity was observed in 104/180 (57.8%) and 86/227 (37.9%) patients, respectively (p < 0.001). In multivariate analysis, adjusted ORs were 2.30 for HPV16 positivity (95% CI 1.36–3.89, p = 0.002), 3.29 for HPV18 positivity (95% CI 1.40–7.73, p = 0.006), and 2.01 for abnormal cervical cytology (95% CI 1.24–3.25, p = 0.005). Recorded CIN2+ was 15/180 (8.3%) in the condyloma-positive group and 7/227 (3.1%) in the condyloma-negative group in the overall cohort; in the biopsy-restricted analysis, CIN2+ was 15/82 (18.3%) and 7/41 (17.1%), respectively. Conclusions: Vulvar condyloma was independently associated with abnormal cervical cytology and high-risk HPV infection, particularly HPV16/18 positivity. These robust associations suggest that vulvar condyloma may represent a clinically visible marker of concurrent cervical HPV-related disease. Careful cervical evaluation is warranted in women presenting with vulvar condyloma, whereas CIN2+ findings should be interpreted cautiously until confirmed in larger prospective cohorts with standardized histopathological verification. Full article

Background: Women treated for cervical intraepithelial neoplasia grade 2 (CIN2) face an increased risk of disease recurrence due to persistent or newly acquired human papillomavirus (HPV) infections, suggesting a potential role for adjuvant HPV vaccination. While a growing body of literature evaluates the outcomes of HPV vaccination following a large loop excision of the transformation zone (LLETZ) for high-grade squamous intraepithelial lesions (CIN2–3), data specifically focused on isolated CIN2 remain limited. This study aims to evaluate the clinical efficacy of the nonavalent HPV vaccine (9vHPV) as an adjuvant strategy to reduce CIN2+ recurrence in women undergoing LLETZ for histologically confirmed, isolated CIN2. Methods: Between November 2017 and November 2024, women undergoing LLETZ for histologically confirmed CIN2 received their first dose of adjuvant 9vHPV within one month of surgery. Patients who achieved double-negative co-testing (Pap test and high-risk HPV DNA test) at the 6-month post-LLETZ follow-up were included in the study group. Conversely, patients with at least one positive test result at 6 months were excluded to rule out residual disease. The study group underwent a subsequent Pap smear at 12 months and a full co-test at 18 months post-surgery; upon achieving negative results through the 18th month, patients returned to the organized screening program. The primary outcome was the recurrence rate, defined as histologically confirmed CIN2+ occurring more than 6 months post-treatment. It was compared against an unvaccinated historical control group treated with LLETZ prior to the study period. The secondary outcome evaluated the prevalence of HPV genotypes at baseline and at the time of recurrence. Results: In the vaccinated group, 3 women (2.03%) experienced CIN2+ recurrence compared to 6 women (5.71%) in the unvaccinated control group. This represents an absolute risk difference of 3.69% and a relative risk reduction of 64.6%, though the difference did not reach statistical significance via Fisher’s exact test (p = 0.165). In the study group, two recurrences were detected at 18 months (associated cytologies: ASC-H and LSIL; genotypes: HPV 51/53 and 16, respectively) and one at four years (cytology: HSIL; genotype: HPV 33/58). In the control group, recurrences occurred at 12 months (n = 3), 18 months (n = 2), and four years (n = 1). Associated cytology revealed HSIL in three cases, ASC-H in one case, LSIL in one case, and ASCUS in the final case. The corresponding HPV genotypes were 16 (two cases), 18, 51, 31 and 56 (co-infection), and one case of high-risk HPV, not further genotyped. Conclusions: Adjuvant 9vHPV administration after LLETZ for isolated CIN2 was associated with a clinically substantial lower absolute recurrence rate (2.03% vs. 5.71%, corresponding to a 64.6% relative risk reduction). Although this reduction did not achieve statistical significance ($p=0.165$) due to our small sample size and a low baseline recurrence rate in this isolated cohort, the effect size is highly comparable to broader CIN2+ studies. The study was likely underpowered to prove statistical significance, and larger multi-center studies are required to confirm the statistical value of adjuvant vaccination specifically in isolated CIN2 lesions. Full article

Cervical cancer remains a major global health challenge and a leading cause of gynecological cancer-related mortality, particularly in developing countries. Although persistent human papillomavirus infection is the primary driver of cervical carcinogenesis, host factors such as immune dysregulation and microbiome dysbiosis may contribute to disease progression. Corisin is a microbiota-derived peptide implicated in epithelial injury and fibrosis, but its role in cervical neoplasia is unknown. To investigate its potential involvement, circulating corisin levels were measured in 27 women with cervical intraepithelial neoplasia (CIN) or cervical cancer and compared with those in 15 healthy women. Corisin localization in cervical carcinoma tissues was examined by immunohistochemistry, and its biological effects were evaluated in HeLa cells. Circulating corisin levels were significantly elevated in patients with CIN and cervical cancer, with the highest levels observed in CIN3 and cervical squamous cell carcinoma. Corisin was detected within cervical carcinoma tissues in intracellular and extracellular compartments adjacent to tumor cells. In HeLa cells, corisin accumulated in mitochondria, impaired cell-cycle progression, induced apoptosis, increased p21 expression, and promoted epithelial–mesenchymal transition-like morphological changes. These findings suggest that corisin is elevated from the early stages of cervical neoplasia, is present within the cervical tumor microenvironment, and may contribute to pathogenic cellular processes associated with cervical cancer progression. Full article

Background: Cervical cancer screening uptake in Romania remains below 20%, with invasive sampling cited as a major participation barrier. Urinary HPV testing is a non-invasive alternative, but data from Eastern European populations are scarce and reporting stratified by histological grade is inconsistent. Objectives: To evaluate the agreement between paired urinary and clinician-collected cervico-vaginal HPV testing, and to assess the diagnostic performance of urinary HPV testing for biopsy-confirmed cervical intraepithelial neoplasia grade 2 or worse (CIN2+). Methods: Prospective cross-sectional study in three outpatient obstetrics and gynecology clinics (May 2025–May 2026). A total of 230 women aged 25–70 years provided paired cervico-vaginal (PreservCyt^®) and first-void urine (Colli-Pee^®) specimens. To capture the full spectrum of disease probability, participants were recruited across three clinical scenarios: primary screening, cytology triage and HPV-positive triage. A multiplex RT-PCR assay targeted a total of 14 high-risk HPV genotypes, providing separate identification for HPV16 and HPV18, alongside a pooled detection for the remaining 12 high-risk strains. Colposcopy-guided cervical biopsy served as the reference standard. Results: Paired hrHPV testing achieved substantial agreement (κ = 0.696, 95% CI 0.604–0.788), with higher genotype-specific concordance for HPV16 (κ = 0.755) and HPV18 (κ = 0.789). Discordance was directionally asymmetric (30 cervical-positive/urine-negative versus 4 urine-positive/cervical-negative; McNemar p < 0.001). For biopsy-confirmed CIN2+ (59 of 230; 25.7%), urinary hrHPV showed a sensitivity of 86.4% (95% CI 75.5–93.0), specificity 56.7%, positive predictive value 40.8% and negative predictive value 92.4%, compared with 91.5%, 43.3%, 35.8% and 93.7% for cervico-vaginal testing. Urinary HPV positivity increased monotonically with histological severity (25.0% no-lesion, 69.0% CIN1, 86.4% CIN2+; linear-by-linear p < 0.001). Conclusions: Urinary HPV testing demonstrates substantial agreement with clinician-collected sampling, near-equivalent negative predictive value, and a robust dose–response with histological severity. It is a clinically credible non-invasive entry point for a triage cascade in settings such as Romania, where low participation rather than analytical performance is the principal screening barrier. Full article

Background: Colposcopy is a widely used clinical and diagnostic tool for detecting cervical intraepithelial neoplasia grade 2 or higher (CIN2+). This paper aims to analyze the diagnostic accuracy, pooled sensitivity, specificity, likelihood ratios, and overall diagnostic performance of colposcopy. Methods: A systematic review of papers on diagnostic accuracy, preregistered in PROSPERO (CRD420251028776), was conducted following PRISMA-DTA guidelines. Statistical analyses were performed using SPSS 29 and METADISC 2.0. Study quality and risk of bias were assessed using QUADAS-2. Results: A total of 49 studies, including 141,355 colposcopic examinations, were included in the final analysis. The overall sensitivity was 0.745 (95% CI: 0.684–0.797) and specificity was 0.831 (95% CI: 0.770–0.879). The diagnostic odds ratio was 14.388 (95% CI: 9.673–21.400). The positive likelihood ratio was 4.419 (95% CI: 3.260–5.991). Conversely, the negative likelihood ratio was 0.307 (95% CI: 0.249–0.378). The area under the curve was 0.8569. Significant heterogeneity was observed across studies (I² > 93.2%). Conclusions: Colposcopy demonstrates moderate-to-high diagnostic accuracy in detecting CIN2+ lesions, with a good balance between sensitivity and specificity. However, significant variability exists among studies, highlighting the need for the implementation of standardized colposcopic criteria, improved examiner training, and adjunctive diagnostic methods such as HPV testing and ancillary techniques to enhance accuracy and reduce false positives and false negatives. Future research should focus on minimizing interobserver variability and refining diagnostic algorithms to optimize colposcopic performance. Full article

Background and Objectives: Persistent human papillomavirus (HPV) infection is associated with the development of cervical intraepithelial neoplasia and cervical cancer. In women with low-grade cervical lesions, a conservative management approach is commonly recommended. However, a subset of patients may experience lesion progression, which can also be accompanied by psychological distress. Adjuvant therapies during the surveillance period have gained increasing clinical interest. This consensus aims to provide multidisciplinary, expert-based recommendations on the use of a Coriolus versicolor-based vaginal gel in HPV-positive women with low-grade cervical lesions. Materials and Methods: A rapid systematic review was conducted in accordance with PRISMA guidelines, and the level of evidence was assessed using SIGN criteria. Subsequently, a multidisciplinary panel of experts formulated and evaluated consensus statements and recommendations using the nominal group technique and a voting process. Results: All statements reached consensus, with agreement levels exceeding 80%. Experts concluded that available evidence reports potential benefits of a Coriolus versicolor-based vaginal gel in HPV-positive women with low-grade cervical lesions, since it has demonstrated increased lesion regression and viral clearance rates. These benefits may be more pronounced in specific subgroups, particularly women over 40 years of age. Limited studies also suggest a positive effect on vaginal microbiota, which may contribute to both vaginal health and HPV clearance, as well as a reduction in perceived stress. The experts emphasized the importance of patient education, shared decision-making, and addressing psychosocial aspects, including emotional well-being and sexual health. Conclusions: This consensus provides a multidisciplinary perspective on the management of HPV-positive women with low-grade cervical lesions, highlighting the adjuvant role of a Coriolus versicolor-based vaginal gel during surveillance. Although current evidence suggests potential clinical benefits, further high-quality, independent studies are needed to corroborate these findings. Full article

Background/Objectives: Cervical intraepithelial neoplasia (CIN) exhibits heterogeneous clinical behavior, with some lesions regressing spontaneously, whereas others persist or progress to higher-grade disease. Identifying biomarkers that reflect lesion dynamics remains a major clinical challenge. This study aimed to evaluate the clinical significance of CD86 expression in cervical lesions by examining longitudinal changes and determining whether temporal alterations in CD86 expression are associated with lesion regression and epithelial-associated immune dynamics. Methods: Cervical samples were collected from patients with CIN, and gene expression was analyzed using reverse transcription–quantitative PCR. Longitudinal analyses were performed using paired samples to evaluate the temporal changes in CD86 expression. Regression status and time to regression were assessed, and associations with CD86 changes were evaluated using receiver operating characteristic analysis, logistic regression, and Cox proportional hazards models. Longitudinal patterns were further characterized using a spaghetti plot and slope analyses. Results: Baseline CD86 expression did not associate with regression status or CIN grade. However, longitudinal changes in CD86 expression differed significantly between the regression and non-regression group. CD86 change demonstrated moderate predictive performance for regression and was significantly associated with both regression and shorter time to regression. Longitudinal analyses revealed distinct temporal patterns between the regression and progression groups. Baseline CD86 expression was strongly correlated with FOXP3 expression, whereas CD86 dynamics were not independently associated with lymphocyte-related markers. Conclusions: Longitudinal changes in CD86 expression are significantly associated with lesion regression in CIN and may reflect lesion-associated immune dynamics during follow-up, particularly within epithelial-derived cervical cytology specimens. Full article

Background/Objective: Cervical intraepithelial neoplasia grade 2 (CIN2) shows heterogeneous clinical behavior, with substantial rates of spontaneous regression under active surveillance. Reliable molecular biomarkers are needed to distinguish regressive from transforming lesions and reduce overtreatment. We evaluated the prognostic role of host and viral DNA methylation, alone and combined with HPV genotyping, in predicting CIN2 regression. Methods: This subanalysis derives from a prospective, multicenter Italian cohort of women with histologically confirmed CIN2 managed conservatively. Among 319 enrolled women, 134 with single HPV infections and valid host (FAM19A4/miR124-2) and viral (HPV L1 region) methylation results were included. HPV genotyping was performed with partial stratification (HPV16/18 vs. non-16/18). Clinical outcomes at 24 months were classified as regression versus persistence/progression. Logistic regression models assessed associations between biomarkers and regression. Results: At 24 months, 50% of women showed regression. Host and viral methylation positivity rates were more frequent in non-regressive lesions (40.3% vs. 19.4%, p = 0.01, and 52.2% vs. 32.8%, p = 0.02, respectively). Negative host methylation was significantly associated with regression (Odds Ratio OR = 0.37, 95% CI 0.17–0.81, p = 0.02), as was negative viral methylation (OR = 0.47, 95% CI 0.23–0.96, p = 0.04). Conclusions: Both host and viral methylation are inversely associated with CIN2 regression. Combining methylation markers did not substantially improve predictive accuracy; however, methylation negativity emerged as a potential molecular reassurance marker. When integrated with HPV genotyping, the highest probability of regression was observed among women with non-HPV16/18 infections and negative methylation results. These results endorse DNA methylation testing as a molecular tool for the conservative management of CIN2. Full article

Human papillomavirus type 53 (HPV53) is one of the most prevalent HPV genotypes in China, frequently detected in cervical intraepithelial neoplasia and cervical cancer, yet remains outside the coverage of all currently available prophylactic vaccines and is relatively understudied. This study performed a comprehensive analysis of HPV53 clinical infection profiles, genomic diversity, and T-cell epitopes to inform therapeutic vaccine development. Clinical analysis of 158 HPV53-positive patients showed that infections were most prevalent in women aged 40–59 years, with persistent infection identified in 13.3% participants and a subset of cases associated with cervical lesions. Genomic analysis of 134 HPV53 isolates identified four lineages (A-D, with lineage D further subdivided into four sublineages, and an overall nucleotide variability of 4.4%. E2 was the most variable protein while E7 was the most conserved. Immunoinformatic prediction identified 176 HLA class I-restricted T-cell epitopes across E6, E7, E1, and E2, from which 20 candidates were selected for experimental validation. Ten demonstrated strong HLA binding affinity in vitro, and murine immunization identified a E6 peptide VYNFAYTDL as an immunodominant epitope. Three validated epitopes exhibited sequence overlap with 12 to 13 of other 13 high-risk HPV genotypes, suggesting their potential as broadly cross-reactive targets. These findings clarify the genomic diversity and immunogenic epitope landscape of HPV53, providing a foundation for the rational design of therapeutic vaccines. Full article

Cervical intraepithelial neoplasia grade 1 (CIN1) is usually managed conservatively, but uncertainty remains about the subsequent risk of clinically significant high-grade disease, particularly after repeated CIN1. We conducted a retrospective population-based cohort study using anonymized cervical cytology, HPV, and histopathology records from Northern Norway from 2011 to 2025. We described temporal trends in screening-related outcomes and estimated the 5-year risk of CIN3+ after histologically confirmed CIN1 diagnosed in a single calendar year or in two consecutive calendar years. Across 2011–2025, the annual datasets comprised 334,471 screening records; 35,796 had ASC-US+ cytology (10.7%), 29,723 had a positive HPV test (8.9%), 35,416 underwent biopsy (10.6%), and 7870 were diagnosed with CIN2+ (2.4%). HPV positivity increased from 0.9% in 2011 to 15.7% in 2025, whereas CIN2+ detection peaked at 3.1% in 2018 and declined to 1.8% in 2025. In person-based analyses, the 5-year risks after CIN1 diagnosed in a single calendar year versus two consecutive calendar years were 4.3% versus 3.4% for CIN3+, 0.2% versus 0.1% for cervical cancer, and 15.4% versus 14.3% for CIN2+. Repeated CIN1 was not associated with higher subsequent CIN3+ risk, supporting conservative, risk-based follow-up after CIN1 biopsy. Full article