Search Results (233)

Objective: Given the variability in conization cone volume, specimen fragmentation, and histopathological excisional margin status, even in optimally performed procedures, the study aimed to assess the factors affecting these characteristics. Methods: This cross-sectional study based on retrospectively collected data, included 179 women who underwent large-loop excision of the transformation zone (LLETZ). The impact of age, menopausal status, parity, high-risk human papillomavirus (hr-HPV) status, transformation zone (TZ) type, conization indications, and histopathological characteristics on cone volume, fragmentation, and margin status was assessed. Results: Cone volume was positively associated with increased parity and was significantly larger in women with resection margin involvement and complete lesion excision compared to those with unspecified margins. No significant correlations were found between cone volume and age, menopausal status, hr-HPV status, TZ type, indications for LLETZ, or specimen fragmentation. Specimen fragmentation demonstrated no correlations with parity, menopausal status, LLETZ indications, or hr-HPV status, but it was more prevalent among women aged 31–35 years. Absence of fragmentation was linked to clear resection margins, while fragmentation correlated with margin involvement. Complete excision was more frequent in women with high-grade squamous intraepithelial lesions (HSIL) cytology, although lesions extended to the specimen margin primarily in specimens with biopsy-confirmed HSIL cervical intraepithelial neoplasia (CIN) 3. None of the evaluated factors were independent predictors of complete lesion excision or margin involvement. Conclusions: Cone volume, fragmentation, and margin status are clinically relevant LLETZ outcomes, although no independent predictors were identified after adjustment. Larger prospective multicenter studies are needed to determine how oncologic adequacy can be balanced with preservation of cervical function. Full article

Background/Objectives: Excisional treatment is effective for cervical intraepithelial neoplasia grade 2 or 3 (CIN2–3), but residual or recurrent high-grade disease remains clinically important. This focused systematic review evaluated post-treatment high-risk human papillomavirus (hrHPV) testing as a test of cure and compared it with cytology and resection-margin status. Methods: PubMed/MEDLINE was searched and supplemented by structured citation checking and targeted verification, with supplementary Embase and CENTRAL searches conducted during peer review; the review was not prospectively registered. Mixed-grade cohorts were retained only when a high-grade subgroup was extractable or for supportive qualitative evidence. Results: Fifteen primary studies enrolled 21,932 treated women, of whom 18,992 contributed to endpoint-specific analyses. Explicit CIN2+/CIN3+/HSIL+ event rates were 1.9–6.8% in most studies, with 11.8% in one earlier intensively verified cohort; higher rates in other reports reflected any-grade CIN or composite outcomes and were not treated as CIN2+. In the subset reporting directly comparable accuracy measures, hrHPV testing was generally more sensitive than cytology and negative predictive values were 98.0–100%. These values require caution because recurrence prevalence was low and histological verification was incomplete in several cohorts. Five studies were judged at low, eight at unclear, and two at high overall risk of bias for their diagnostic-accuracy contributions. Conclusions: The evidence supports hrHPV-based risk stratification and reduced-intensity surveillance after a negative test, but not unqualified return to routine population screening. Standardised prospective studies with uniform CIN2+ endpoints and complete verification remain needed. Full article

Background/Objectives: Distinguishing invasive cervical cancer from high-grade cervical intraepithelial neoplasia (CIN) before histopathology remains difficult. We evaluated routine blood-based parameters for this distinction and developed and internally validated a parsimonious prediction model, testing its incremental value over age. Methods: In this retrospective diagnostic accuracy study with two-gate (case–control) sampling, we analyzed 137 unique patients with histopathologically confirmed cervical cancer and 238 with high-grade CIN after duplicate removal. A four-variable model (age, CEA, neutrophil-to-lymphocyte ratio (NLR), and hemoglobin) was developed and internally validated by bootstrap optimism correction, calibration, and decision-curve analysis, with age-matched and subgroup sensitivity analyses. Results: The strongest single discriminators were age (AUC 0.826), C-reactive protein (0.805), and albumin (0.772). The continuous model showed an apparent AUC of 0.859 (optimism-corrected 0.853; calibration slope 0.962; Brier 0.136). The gain over age alone was statistically significant but modest (ΔAUC +0.027; DeLong p = 0.015). After 1:1 age matching, age no longer discriminated (AUC 0.49), whereas the model retained moderate discrimination (AUC 0.686), with NLR independent. Performance was lower for CIN 3 versus early-stage cancer (AUC 0.759). Conclusions: The model may provide adjunctive risk-stratification information, but clinical implementation requires external validation in prospectively assembled cohorts; the findings are hypothesis-generating. Full article

Cervical cancer remains the leading cause of cancer-related mortality among women in Nepal, where national screening coverage is approximately 16%. This study evaluated the feasibility of a community-based, door-to-door self-sampling strategy for high-risk human papillomavirus (hrHPV) detection in an urban municipality of central Nepal and assessed hrHPV prevalence, genotype distribution, screening outcomes, and associated demographic factors. A cross-sectional study was conducted between September 2023 and May 2024 in Ward No. 3 of Lalitpur Metropolitan City. Women aged 30–60 years were recruited through trained community health workers, provided education and home-based self-sampling kits, and completed a demographic questionnaire. Dry cervical swabs from 418 participants were tested for hrHPV. Women with positive results underwent visual inspection with acetic acid (VIA), followed by colposcopy, biopsy when indicated, and thermal ablation for confirmed precancerous lesions. Overall participation was 64.1%, and hrHPV prevalence was 10.3%. Non-16/18 hrHPV genotypes predominated (55.8%), followed by HPV16 (20.9%). Women aged > 50 years were more likely to be hrHPV- and VIA-positive (OR = 7.39, p = 0.02). Six pre-cancer cases were identified: five cervical intraepithelial neoplasia (CIN1) and one CIN3 case. Community-based hrHPV self-sampling was found to be feasible and achieved effective linkage to triage and treatment, supporting its consideration for strengthening cervical cancer screening in Nepal. Full article

Background/Objectives: Norway has transitioned from cytology-based to HPV-based cervical screening. We examined long-term trends in histologically confirmed cervical intraepithelial neoplasia grade 2 or worse (CIN2+), grade 3 or worse (CIN3+), and cervical squamous cell carcinoma (SCC) among women aged 40–69 years in Troms and Finnmark, a population largely ineligible for programme-based HPV vaccination. Methods: This retrospective, regional repeated cross-sectional study used routine pathology records from the University Hospital of North Norway from 1998 to 2025. Cervical samples obtained through primary screening, follow-up, and clinical indications were included. The most severe histological diagnosis per woman and calendar year was retained. Annual detection rates were calculated per 1000 women with at least one registered cervical sample. Temporal trends were assessed using negative binomial regression with annual endpoint counts as outcomes and the annual cervical-sampling denominator as an offset. All SCC diagnoses were included irrespective of symptoms or mode of detection. Results: The study comprised 350,868 annual woman-records, 3049 CIN2+, 1596 CIN3+, and 143 SCC diagnoses. CIN2+ detection increased significantly over time (rate ratio [RR] per calendar year, 1.025; 95% confidence interval [CI], 1.016–1.035; p < 0.001), whereas CIN3+ detection decreased (RR, 0.987; 95% CI, 0.980–0.995; p = 0.002). No significant temporal trend was observed for SCC (RR, 0.995; 95% CI, 0.971–1.020; p = 0.704). Conclusions: CIN2+ detection increased, CIN3+ detection decreased, and SCC showed no significant temporal trend during substantial changes in screening and diagnostic practice. The independent contributions of screening modality, screening intervals, diagnostic activity, histopathological practice, local HPV mRNA-based quality assurance, and denominator changes cannot be separated. The reported rates represent regional pathology detection relative to cervical-sampling activity rather than population incidence. Full article

Background: Romania has one of the highest cervical cancer incidence and mortality rates in the European Union (EU) and one of the lowest levels of screening participation. We examined eight years of screening activity at an accredited centre in Bihor County, north-western Romania, encompassing the pre-pandemic period (2018–2019), the COVID-19 pandemic (2020–2021), the post-pandemic recovery (2022–2023) and the transition from primary cytology to primary human papillomavirus (HPV) DNA screening (2024–2025). Methods: This retrospective, single-centre study included 17,807 de-identified screening-episode records collected between 2018 and 2025 at Pelican Clinical Hospital, Oradea. Cytology was the primary screening test in the cytology era (2018–2023), whereas high-risk HPV (HR-HPV) DNA testing (cobas HPV Test, Roche, Pleasanton, CA, USA) with reflex cytology was used in the HPV-primary era (2024–2025). Screening activity was expressed relative to the provider’s registered administrative catchment of 65,978 women. Because quarterly counts were markedly overdispersed, changes in screening volume were analysed using negative-binomial incidence-rate ratios (IRRs) and a segmented negative-binomial interrupted time-series; cytological positivity was evaluated using age-adjusted logistic regression and the Cochran–Armitage trend test. Results: The number of screening episodes recorded over eight years corresponded to 27.0% (95% confidence interval [CI] 26.6–27.3) of the registered catchment, while annual throughput never exceeded 5.2%. Mean monthly screening volume declined from 264.5 tests in the pre-pandemic period (2018–2019) to 88.6 during the pandemic (2020–2021; IRR 0.335, 95% CI 0.177–0.634; 66.5% reduction; p < 0.001), corresponding to an estimated deficit of approximately 3700 tests; the interrupted time-series estimated an immediate 86% reduction at lockdown onset. Activity recovered to 61% of the pre-pandemic rate during the post-pandemic recovery (2022–2023; IRR 0.614, 95% CI 0.482–0.783) and to 90% in the HPV-primary era (2024–2025; IRR 0.898, 95% CI 0.733–1.100), coinciding with the transition to primary HPV screening. All primary HPV tests produced valid results, compared with an annual unsatisfactory-sample rate of 2.9–4.2% during primary cytology. Cytological positivity remained stable during 2018–2023, and the cytological high-grade squamous intraepithelial lesion (HSIL) detection rate per 1000 screened did not change significantly during the pandemic, although absolute HSIL detections declined with screening volume. In 2024–2025, HR-HPV positivity was 22.8% (1301/5700; 95% CI 21.8–23.9), and 47.9% of HPV-positive women had abnormal reflex cytology. Conclusions: The pandemic substantially reduced screening activity at a provider already operating with low throughput relative to its registered catchment. Activity subsequently returned to near pre-pandemic levels during the period coinciding with the introduction of primary HPV screening, which also improved primary-sample adequacy. However, the absence of persistent patient linkage and of follow-up data from colposcopy, histology and treatment precluded estimation of population-based coverage, screening intervals and detection of histologically confirmed cervical intraepithelial neoplasia grade 3 or worse (CIN3+). The findings support population-based invitation and recall, clearly defined age-specific screening and follow-up algorithms, self-sampling, targeted catch-up after pandemic-related delays and longitudinal evaluation using histologically confirmed CIN3+ as the principal clinical endpoint. Full article

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: 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: 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/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

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