Search Results (109)

Background: Although HPV vaccination is highly effective in the primary prevention of cervical cancer, its potential role in women already diagnosed with HPV-associated cervical dysplasia remains uncertain. This study aimed to evaluate the association between post-diagnosis HPV vaccination and short-term clinical outcomes in HPV-positive women with cervical dysplasia. Methods: Women aged ≥18 years with abnormal cervical screening results suggestive of squamous intraepithelial lesions and high-risk HPV positivity were retrospectively evaluated. High-grade disease was defined as histologically confirmed CIN2/3. HPV vaccination (9-valent) was recommended to all eligible patients at the time of diagnosis. Vaccination status was primarily analyzed as vaccinated (≥1 dose) versus unvaccinated; additionally, dose-stratified analyses (0, 1–2, and 3 doses) were performed to explore potential dose–response relationships. Results: A total of 392 women were included (173 unvaccinated and 219 vaccinated). At 12 months, regression occurred in 51.1% of vaccinated patients compared with 41.0% of unvaccinated women (OR 1.50, 95% CI 1.02–2.20, p = 0.04). A dose–response pattern was observed, with regression rates of 41.0% in unvaccinated patients, 46.1% in partially vaccinated patients, and 54.6% in fully vaccinated patients (p for trend = 0.012). In the HSIL subgroup, regression occurred in 49.0% of vaccinated women versus 33.8% of unvaccinated patients (OR 1.88, 95% CI 1.01–3.52, p = 0.047). When stratified by treatment modality, vaccination was significantly associated with higher regression in the non-LEEP cohort (OR 1.67, p = 0.04) but not in the LEEP cohort (p = 0.22). In multivariable analysis adjusting for age, smoking, HPV genotype, baseline histopathologic grade (CIN1 vs. CIN2/3), and treatment modality, HPV vaccination remained independently associated with regression (aOR 1.55, 95% CI 1.05–2.30, p = 0.028). Conclusions: Post-diagnosis HPV vaccination was associated with a higher probability of cervical dysplasia regression at 12 months, particularly among women with baseline HSIL. These findings suggest that HPV vaccination may provide a beneficial adjunct effect in the clinical management of HPV-associated cervical dysplasia. Prospective studies are required to confirm these observations and clarify the mechanisms underlying this association. Full article

Objective: The aim of this study was to evaluate the positive predictive value of endocervical curettage (ECC) during colposcopic examination in a dysplasia unit since the implementation of the new cervical cancer screening program in Germany (January 2020). Methods: A total of 202 patients who presented for colposcopy at the Dysplasia Unit of the University Hospital Aachen, Germany, between January 2020 and October 2023, who had cervical intraepithelial neoplasia 1+ (CIN1+) in the endocervical curettage and received a loop-excisional procedure of the cervix (LEEP), were included in a retrospective cohort analysis using machine learning techniques (random forest analysis and leave-one-out cross-validation). Results: There was a low agreement between the results of the ECC and the CIN status after LEEP (kappa 0.0239). A positive result in the histological specimen of the excisional procedure of the cervix (CIN2+) was obtained in 73.7% in case of CIN1 detection in the ECC, 69.4% in case of CIN2 detection in the ECC, and 80.6% in case of CIN3 in the ECC. In the multivariate analysis, the result of colposcopy and the transformation zone, especially combined (kappa 0.259, p = 0.0004), had the highest predictive value with regard to the CIN status. Conclusions: ECC is associated with a low agreement rate in comparison to the final histological result of the LEEP, which should be kept in mind when counseling patients. A finding of CCIN1in an ECC obtained during colposcopy following abnormal HPV-based cervical cancer screening results should be considered an indication of a possible intracervical dysplasia. Full article

Objectives: The TNM staging system for distal cholangiocarcinoma (dCCA) has limited accuracy due to its anatomical basis. This study developed a prognostic model integrating inflammatory-nutritional markers and tumor biomarkers to improve risk stratification. Methods: We analyzed 208 dCCA patients undergoing pancreaticoduodenectomy (2017–2024). Independent prognostic factors for overall survival (OS) were identified via Cox regression, including tumor marker (corrected CA19-9) and host status markers (PLR, CAR, and PNI). A nomogram was constructed and evaluated using calibration, ROC, and DCA. Patients were risk-stratified using the model’s score. Results: Four independent factors were identified: corrected CA19-9 (HR = 2.438), PLR (HR = 2.041), CAR (HR = 2.477), and PNI (HR = 0.415). The nomogram showed excellent discrimination for 1-, 3-, and 5-year OS (AUC: 0.847, 0.824, 0.858), good calibration, and clinical utility per DCA. Risk stratification significantly distinguished high-risk (n = 110) from low-risk (n = 98) groups (log-rank p < 0.0001). Discussion: This multidimensional model (tumor burden, inflammation, nutrition) outperforms TNM staging, highlighting host systemic status. Despite its single-center retrospective design, it shows promise for personalized risk assessment. Conclusion: The CINS (Cholangiocarcinoma Inflammation–Nutrition Score) accurately predicts prognosis and effectively risk-stratifies dCCA patients, aiding personalized treatment planning. Full article

Background: Cervical cancer is the second most prevalent malignancy among South African women, with high-risk human papillomavirus (HPV) infection as a critical risk factor. HPV plays a central role in cervical carcinogenesis, particularly in high-grade squamous intraepithelial lesions (HSIL). Increased programmed death ligand 1 (PD-L1) expression has been implicated in cervical carcinoma tumorigenesis. Using immunohistochemistry, this study investigated the correlation between high-risk HPV-driven cervical intraepithelial neoplasia (CIN) and PD-L1 expression. Methods: An analytical cross-sectional study was conducted on archival tissue from the Department of Anatomical Pathology, University of Pretoria (2018–2021). Formalin-fixed paraffin-embedded tissues from loop electrosurgical excisions, cone biopsies, punch biopsies, and polypectomies were analysed. PD-L1 expression was assessed using the combined proportion score (CPS). Three pathologists independently evaluated histological grade, p16 immunohistochemistry, and PD-L1 expression. Results: Among 108 cases (mean age: 37.36 years), 89.8% were CIN 3, 9.3% CIN 2, and 0.9% CIN 2–3. p16 was positive in 97.2% of cases. PD-L1 expression (CPS ≥ 1) was observed in 9.3% of cases, with a mean CPS of 1.57%. No significant association was found between PD-L1 expression and CIN grade (p = 0.6433, Cramer’s V = 0.1191) or between PD-L1 and p16 positivity (p = 1, Cramer’s V = 0.05976). Conclusions: This study demonstrates no correlation between PD-L1 expression and high-risk HPV-driven high-grade CIN. These findings suggest that immune checkpoint inhibition targeting PD-L1 may have limited therapeutic relevance in HSIL among South African women. Full article

Assisted reproductive technologies (ART) use has increased over the past decades. However, reports concerning ART’s low efficiency continue to emerge, citing causes related to lower embryo quality and pregnancy rates compared to their in vivo counterparts. One of the setbacks of ART is oxidative stress, which can impair embryo developmental rates. Mitochondrial redox and energetic homeostasis determine both cell survival and death, so mitochondria are a key target for therapeutic intervention strategies. In the present work, our objective was to improve the quality of viable embryos by adding new mitochondria-targeted antioxidants in the embryo culture media to reduce oxidative stress. Two naturally derived antioxidants synthesized by our team, AntiOxBEN₂ and AntiOxCIN₄, based on hydroxybenzoic and hydroxycinnamic scaffolds, respectively, were studied in two different experimental protocols (here called experiments). The first experiment investigated the effects of the antioxidants on embryo development to determine their optimal concentrations. The first assay of the first experiment focused on the effects of AntiOxCIN₄ at concentrations of 1, 2.5, and 10 μM, while the second assay focused on the effects of AntiOxBEN₂ at the same concentrations. A control group without supplementation was run simultaneously. The second experiment aimed to compare the best concentrations of these antioxidant molecules in the embryo culture media and their effect on embryos’ resistance to vitrification/warming. In each experiment, the embryos were morphologically evaluated, and the total and viable cell numbers were examined. Reactive oxygen species (ROS) and mitochondrial polarization were also evaluated using specific fluorescent dyes. In experiment 1, an increased embryo quality was identified by using 2.5 μM AntiOxCIN₄ (p = 0.03) and 2.5 μM AntiOxBEN₂ (p = 0.001). Moreover, blastocysts supplemented with 2.5 μM AntiOxCIN₄ had higher viability (p = 0.008), while those supplemented with 2.5 μM AntiOxBEN₂ presented a greater total cell number (p = 0.01). An improvement in embryo cryosurvival following the supplementation during the culture process with either antioxidant was identified in experiment 2, with superior expansion scores after vitrification/warming and culture (2.5 μM AntiOxCIN₄, p = 0.056 and 2.5 μM AntiOxBEN₂, p = 0.059). In conclusion, both AntiOxCIN₄ and AntiOxBEN₂ had a beneficial effect on embryo development and cryosurvival, suggesting a potential intervention to reduce oxidative stress in assisted reproductive technologies. Full article

Background: Cervical intraepithelial neoplasia (CIN) represents a precancerous condition whose effective management is crucial for preventing invasive cervical cancer, a disease that remains a leading cause of cancer-related mortality among women worldwide. The long pre-invasive phase of cervical carcinogenesis and the availability of effective screening and treatment procedures make CIN a largely preventable and curable entity. Objectives: This review aimed to analyze therapeutic options applied in CIN, correlating interventions with lesion grade and guideline recommendations, in order to outline a management model adapted to the Romanian clinical setting. Materials and Methods: A structured narrative review of 20 published articles addressing cervical intraepithelial neoplasia (CIN 1–3) published between 2021 and 2023 was performed. Relevant studies were identified through a targeted literature search and analyzed descriptively. This study synthesized data from the recent literature and international clinical guidelines to identify management trends and context-specific adaptations. Results: Extracted variables included lesion grade, reported therapeutic approach (surveillance, excisional, or ablative treatment), reproductive considerations, and patient compliance, with international guidelines used as reference standards. Across the reviewed studies, excisional procedures (conization and LEEP) were predominantly reported for high-grade neoplasia (CIN 2–3), while low-grade lesions (CIN 1) were managed either conservatively or through close surveillance. Treatment decisions described in the literature were strongly influenced by patient age, fertility preservation needs, and obstetric history. Overall, management approaches reported in Romanian and international studies were broadly aligned with current guideline recommendations, although variations were observed in the expectant management of younger patients. Conclusions: The findings emphasize the importance of individualized management in cervical dysplasia, integrating lesion characteristics with patient-specific factors. While international guidelines provide a robust framework, their adaptation to the Romanian healthcare context should prioritize patient education, compliance, and structured post-treatment follow-up strategies. Full article

(1) Background/Objectives: Human papillomavirus (HPV) testing is hypothesised to detect cervical intraepithelial neoplasia grade 3 (CIN3) earlier than cervical cytology, which could translate into several clinical benefits. This study aimed to confirm that HPV testing detects CIN3 lesions of smaller size (or linear extension) and to assess whether this is associated with a decreased risk of stromal microinvasion (≤3 mm) (microinvasive or stage IA1 cervical carcinoma). (2) Methods: The study was conducted in a referral centre for cervical pathology in Italy. Eligible were 3744 patients aged 30–64 years who underwent local excision of the cervix between 1992 and 2021 and were diagnosed with CIN3, with or without microinvasion. Data were analysed using logistic and multinomial regression models. (3) Results: Overall, 1156 (30.9%) CIN3 cases were detected by the HPV test, and 2588 (69.1%) by cervical cytology. The lesion size was smaller in HPV test-detected CIN3 (median, 6 mm; interquartile range (IQR), 4–8 mm) than in cytology-detected CIN3 (median, 7 mm; IQR, 5–9 mm; p < 0.001). HPV test-detected CIN3 was over 50% less likely to have a size >6 mm combined with massive glandular crypt involvement. Stromal microinvasion occurred in 20/1156 (1.7%) HPV test-detected lesions versus 87/2588 (3.4%) cytology-detected lesions (p = 0.006), corresponding to an approximately 50% lower age-adjusted risk. The smaller size of HPV test-detected CIN3 and its lower degree of glandular crypt involvement interacted additively, rather than multiplicatively, in reducing the risk of stromal microinvasion. Over 46% of the association between detection mode and stromal microinvasion was explained by the size/involvement composite variable. (4) Conclusions: HPV testing detects CIN3 lesions of smaller size than cervical cytology. HPV test-detected CIN3 has a lower risk of stromal microinvasion. This association is mediated to a substantial extent by the smaller lesion size and the less extensive glandular crypt involvement, which interact in an additive manner. These findings may have other important clinical implications. First, the prevalence of disease persistence after treatment may decrease. Second, smaller lesions are likely to be treated with more limited excisions. Third, this may contribute to a lower rate of preterm birth in subsequent pregnancies. Full article

(1) Background: Gastroretentive systems are an interesting option for enhancing the bioavailability of weak bases and poorly soluble drugs. The aim of this study was to formulate supramolecular organogels based on cinnarizine (CIN) as a potential gastroretentive system. (2) Methods: The organogels were prepared with different oils in different ratios. Thereafter, their pharmaceutical characteristics and in vitro gastric retention were evaluated through in vitro and in silico simulations. (3) Results: Organogels with different proportions of CIN to oils were successfully obtained. The DSC thermal analysis results demonstrated that all organogels showed gel–sol temperature transitions. The frequency sweep test verified that all organogels presented frequency-independent behavior. Optical imaging revealed longitudinal spherulites of the 1:4 CIN in organogels in all oils. The CIN organogels in all oils (1:4) were observed to float in gastric media during the entire release study. The pharmacokinetic parameters of CIN in peppermint oil (1:4) revealed a close Cmax value to that of the 25 mg immediate-release tablet, but a different AUC. (4) Conclusions: The organogels in all oils floated throughout the release study, establishing their potential as a gastroretentive system. Furthermore, these dosage forms were assessed as a gastric-controlled system through in silico simulations, which enabled prediction of their pharmacokinetic parameters. Full article

Background: Cervical cancer (CC) is the fourth most common malignancy in women around the world, with more than 600,000 new cases registered in 2022 and around 350,000 deaths. It is a growing social problem, especially in developing countries. Almost all cases of cervical cancer are caused by persistent infection with oncogenic high-risk human papillomavirus (HPV). This malignancy usually exhibits a gradual development through well-defined precursor stages, known as cervical intraepithelial neoplasia (CIN) grades 1, 2, and 3, before evolving into invasive carcinoma. In diagnostic practice, several biomarkers have been implemented to improve the detection of high-risk cervical lesions. p16 and Ki-67 greatly aid in identifying HPV-driven dysplasia, but they cannot always reliably distinguish progressive lesions from regressive or transient HPV infections. These limitations highlight the need for novel biomarkers with better predictive accuracy to complement current screening and diagnostic algorithms. ROMO1 has become a possible marker of a high-ROS, high-risk tumor phenotype in a number of cancers. Although oxidative stress, HPV, and cervical carcinogenesis have been linked, nothing is known about ROMO1’s involvement in cervical neoplasia. There is currently a lack of thorough information regarding the expression of ROMO1 in normal vs. precancerous lesions and in cervical cancer, as well as on whether or not its expression is correlated with the severity of the disease. In order to define ROMO1 expression throughout the course of cervical squamous neoplastic development, the current study was created. Methods: We performed immunohistochemical analysis of ROMO1 expression on cervical tissue samples from three groups: healthy cervix (n = 30), cervical intraepithelial neoplasia (CIN) (n = 41), and invasive cervical carcinoma (n = 205). ROMO1 expression in invasive carcinoma was evaluated using an H-score scale. Results: ROMO1 expression was basal in all normal cervix samples (0/30 cases). In contrast, CIN lesions showed 100% ROMO1 expression in the suprabasal layers of abnormal cells in all CIN cases. In invasive cervical carcinomas, ROMO1 expression was heterogeneous. In our cancer cohort (n = 205), ROMO1 H-score showed no significant association with the following: FIGO stage I vs. II vs. III (p = 0.25); histologic grade G1 vs. G2 vs. G3 (p = 0.46); lymphovascular invasion (no vs. yes; p = 0.80); nodal status N0 vs. N1 (p = 0.67); patient age (≤50 y vs. >50 y; p = 0.38). However, ROMO1 expression did vary by histologic subtype (AC vs. ASC vs. SCC; p = 0.02), with SCC enriched for strong staining compared to AC/ASC. With regard to tumor stage (pT stage), pT2a tumors exhibited significantly lower ROMO1 (pT1b1–pT2b; p = 0.035) than pT1b1 (p = 0.04). No other clinicopathologic variable remained significant. Notably, ROMO1 expression was highest in stage I tumors and declined in more advanced stages of cervical carcinoma. Conclusions: These results show a clear pattern of ROMO1 expression across the cervical neoplasia spectrum: it is attenuated in invasive tumors (with a peak in early-stage illness), significantly raised in pre-cancerous CIN lesions, and negligible in normal epithelium. The idea that oxidative stress may be the primary cause of early malignant transformation in the cervix is supported by the noticeable overexpression of ROMO1 in early lesions. For the detection of early-stage cervical carcinoma and high-grade precancerous lesions, ROMO1 may be a useful auxiliary biomarker. Full article

Personalized cancer vaccines are a key strategy for training the immune system to recognize and respond to tumor-specific antigens. Our earlier software release, AutoEpiCollect 1.0, was designed to accelerate the vaccine design process, but the identification of tumor-specific genetic variants remains a manual process and is highly burdensome. In this study, we introduce AutoEpiCollect 2.0, an improved version with integrated genetic analysis capabilities that automate the identification and prioritization of tumorigenic variants from individual tumor samples. AutoEpiCollect 2.0 connects with RNA sequencing and cross-references the resulting RNAseq data for efficient determination of cancer-specific and prognostic gene variants. Using AutoEpiCollect 2.0, we conducted two case studies to design personalized peptide vaccines for two distinct cancer types: cervical squamous cell carcinoma and breast carcinoma. Case 1 analyzed five cervical tumor samples from different stages, ranging from CIN1 to cervical cancer stage IIB. CIN3 was selected for detailed analysis due to its pre-invasive status and clinical relevance, as it is the earliest stage where patients typically present symptoms. Case 2 examined five breast tumor samples, including HER2-negative, ER-positive, PR-positive, and triple-negative subtypes. In three of these breast samples, the same epitope was identified and was synthesized by identical gene variants. This finding suggests the presence of shared antigenic targets across subtypes. We identified the top MHC class I and class II epitopes for both cancer types. In cervical carcinoma, the most immunogenic epitopes were found in proteins expressed by HSPG2 and MUC5AC. In breast carcinoma, epitopes with the highest potential were derived from proteins expressed by BRCA2 and AHNAK2. These epitopes were further validated through pMHC-TCR modeling analysis. Despite differences in cancer type and tumor subtype, both case studies successfully identified high-potential epitopes suitable for personalized vaccine design. The integration of AutoEpiCollect 2.0 streamlined the variant analysis workflow and reduced the time required to identify key tumor antigens. This study demonstrates the value of automated data integration in genomic analysis for cancer vaccine development. Furthermore, by applying RNAseq in a standardized workflow, the approach enables both patient-specific and population-level vaccine design, based on statistically frequent gene variants observed across tumor datasets. AutoEpiCollect 2.0 is freely available as a website based tool for user to design vaccine. Full article

Background/Objectives: Atypical cytological findings in cervical screening, such as ASC-US, ASC-H, and AGC, present a clinical challenge due to their variable risk of underlying high-grade lesions. The precise stratification of this risk is crucial for effective patient management. This study aimed to correlate Bethesda cytology categories with HPV genotyping, including viral load, and histological follow-up to improve risk prediction for cervical intraepithelial neoplasia grade 2 or worse (CIN2+). Materials and Methods: In this retrospective single-center study, we analyzed 407 patients with cytological reports of ASC-US, ASC-H, or AGC. All patients underwent HPV DNA testing with genotyping for 21 types, with viral load quantification for HPV16/18, and subsequent histological verification. Statistical analyses included non-parametric tests, correlation analysis, and multivariate logistic regression to identify independent predictors of CIN2+. Results: The prevalence of CIN2+ differed significantly among the cytological categories: 23.2% in ASC-US, 47.3% in ASC-H, and 19.5% in AGC. ASC-H and a high HPV16 viral load were identified as independent predictors of CIN2+ in the multivariate analysis. An ASC-H result increased the probability of CIN2+ by 2.5 times (aOR = 2.51; 95% CI: 1.28–4.94). For each 1 log10 increase in HPV16 viral load, the risk of CIN2+ increased by 30% (aOR = 1.30; 95% CI: 1.16–1.46). Stratification of ASC-US cases by HPV16 status revealed a dramatically higher positive predictive value (PPV) for CIN2+ in HPV16-positive patients (66%) compared to HPV16-negative patients (12.6%). The AGC category showed the strongest association with glandular pathology, including adenocarcinoma in situ. Conclusions: The combination of cytological findings and HPV16 viral load provides a powerful model for risk stratification. An ASC-H result is a strong independent risk marker, while the clinical significance of ASC-US is fundamentally determined by HPV16 status. These findings advocate for a risk-based management algorithm that integrates liquid-based cytology with extended HPV genotyping and viral load assessments to optimize patient triage and follow-up. Full article

Background/Objectives: To evaluate the effectiveness of expectant management on grades 1 and 2 cervical intraepithelial neoplasia (CIN), including factors associated with regression and progression. Methods: This multicenter study included 561 women managed expectantly and 359 who underwent immediate surgery at eight institutes between 2013 and 2023. Results: Over a 4-year period, 63% and 68% of CIN 1 and CIN 2 cases regressed, and 9% and 14% of cases progressed, respectively. The median regression times were 1.5 years for CIN 1 and 1.2 years for CIN 2. High-risk human papillomavirus (HPV) types, especially HPV 58 (adjusted hazard ratio [HR]: 0.61; p = 0.032) and high-grade initial cytology, atypical squamous cells—cannot exclude high-grade squamous intraepithelial lesion (ASC-H) and high-grade squamous intraepithelial lesion (HSIL) (adjusted HR: 0.3, p < 0.001), were associated with a lower likelihood of regression. Also, hematological disorders reduced the likelihood of regression (adjusted HR 0.39, p = 0.045). In a separate analysis of the immediate surgery group, age in the 30s (p = 0.016) and HPV 16 infection (p = 0.005) were associated with pathologic upgrading at surgery. Conclusions: CIN 1 and 2 usually regress, allowing expectant management for up to 1.5 and 1.2 years, respectively. However, HPV 58 infection or high-grade initial cytology, and hematological disorders are indications for careful monitoring. Patients in their 30s or infected with HPV 16 have a higher risk of pathologic upgrading at surgery. Full article

Objectives: Cervical cancer remains a major health concern worldwide. In women aged ≥ 50, diagnostic accuracy may be compromised due to menopausal changes such as atrophy and squamocolumnar junction displacement. Cytology remains the primary screening tool in many regions, including Poland, although its sensitivity and specificity are limited. This study assessed the concordance between cytological diagnoses of high-grade squamous intraepithelial lesions (HSILs); atypical squamous cells, which cannot exclude HSIL (ASC-H); atypical glandular cells (AGCs); and histopathological verification in women aged ≥ 50 years, highlighting the limitations of current diagnostic pathways. Methods: A retrospective analysis was conducted on women aged ≥ 50 years referred between 2018–2024 with abnormal cytology. All patients underwent colposcopic assessment followed by histopathological verification supported by p16 immunostaining. Cytological and histopathological results were compared. Associations between clinical variables and diagnostic concordance were tested using the chi-square test (α = 0.05). Results: Among 79 patients, histopathology confirmed high-grade squamous intraepithelial lesions with cervical intraepithelial neoplasia grade 2 or higher (HSIL/CIN2+) in 38%. Low-grade squamous intraepithelial lesions with cervical intraepithelial neoplasia grade 1 (LSIL/CIN1) were found in 11%, and vaginal intraepithelial neoplasia grade 1 (VAIN1) in 4%, while 47% demonstrated inflammatory changes or no abnormalities. HSIL cytology showed the highest concordance, whereas AGC was more frequently associated with benign findings. No statistically significant association was detected between cytology accuracy and clinical characteristics (p > 0.05), highlighting the need for further studies in larger cohorts. Conclusions: In women aged ≥ 50, abnormal cytology frequently overestimated the severity of cervical pathology. Reliance on cytology alone may lead to overtreatment or misclassification, particularly in the presence of atrophic or inflammatory changes. Complementary use of human papillomavirus (HPV) genotyping and molecular markers alongside histopathological verification is recommended to enhance diagnostic precision in this population. Full article

Background/Objectives: Cervical intraepithelial neoplasia grade 3 and worse (CIN3+) is a robust surrogate for cervical cancer risk. In Norway, organized cervical screening starts at 25 years of age (25–69 years). Norway introduced school-based HPV vaccination with the quadrivalent vaccine for 12-year-old girls in 2009 (birth cohorts ≥ 1997) with high 3-dose completion, and a catch-up program with the bivalent vaccine for women born 1991–1996 in 2016–2019 with lower uptake. We assessed whether increasing birth-cohort vaccination coverage (defined as ≥1 dose) was followed by reductions in CIN3+ at the age of entry to organized screening (25–29 years). Methods: We conducted a retrospective, population-based time-series of women aged 25–29 years in Troms and Finnmark screened in 2010–2024. CIN3+ was counted per unique woman and expressed per 1000 screened women per year. Cohort-level vaccination exposure was proxied by birth-year eligibility and national coverage (≥1 dose) by calendar year. Temporal trends were assessed using segmented linear regression (2010–2017; 2017–2024). Results: Among 42,253 screening tests, 865 women had CIN3+. CIN3+ rates were stable in 2010–2016 (≈15–24 per 1000), peaked in 2017–2018 (≈26–28 per 1000), and declined to 6.6 per 1000 in 2024 (~75% reduction from the peak). The 2010–2017 trend was not significant (p = 0.244), whereas 2017–2024 showed a significant annual decline (slope −3.04 per 1000 per year; p = 7.4 × 10⁻⁵). The decline coincided with an increase in the vaccinated share of the age group from an estimated 12% in 2017 to 78% in 2024. Cervical cancer was rare throughout and absent in 2024, and the 2023 transition to primary HPV testing did not interrupt the downward trend. Conclusions: As vaccinated birth cohorts—especially those vaccinated before sexual debut—entered organized screening at age 25, CIN3+ in women aged 25–29 years fell markedly. Estimates are based on coverage defined as ≥1 dose; future linkage to individual dose data and HPV type–specific CIN3+ is warranted. Full article

The lymphocystis disease virus (LCDV) is a widespread disease in Mediterranean aquaculture and could lead to losses in fry as well as prevent the sale of adult gilthead seabream (Sparus aurata), affecting both hatchery and on-growing stages. Although LCDV infections are often considered self-limiting, they can lead to severe outcomes due to skin microbiome alterations that promote secondary infections, while also reducing growth and marketability, causing substantial economic losses. Basic biosecurity measures are not successful, and there is no available commercial vaccine. This study evaluated diets supplemented with Origanum vulgare and Cinnamomum zeylanicum essential oils (1% and 2%) in gilthead seabream experimentally infected with LCDV. Preventive feeding (90 days before infection) and therapeutic feeding (initiated at infection) were compared across 11 experimental groups, including infected, recovered, and control groups. Results showed that essential oils were more effective prophylactically than therapeutically, highlighting their protective role when incorporated into diets. Cinnamon-supplemented groups consistently exhibited lower prevalence and mortality than oregano groups. High DNA damage values linked to reduced mortality, particularly in the CIN90.1 group, demonstrated that viral dissemination was most restricted. In conclusion, essential oils modulated LCD progression by influencing viral interactions with DNA damage repair mechanisms, supporting their potential for disease control in intensive aquaculture. Full article