To assess the effectiveness and safety of 5-aminolevulinic acid-based photodynamic therapy (5-ALA PDT) for cervical low-grade squamous intraepithelial lesions (LSIL) patients with high-risk human papillomavirus (HR-HPV) infection and to investigate independent factors that influence the efficacy of PDT treatment. A retrospective analysis was conducted on 530 patients with pathologically confirmed LSIL and HR-HPV infection, treated between March 2017 and January 2024. All patients underwent 5-ALA PDT at an interval of 7-14 days, for a total of 3 to 6 sessions. Follow-ups were conducted 3 and 12 months post-treatment. The efficacy was assessed using HPV genotyping, ThinPrep cytology test (TCT) and colposcopy-directed biopsy. The HPV remission rate was 52.08% at 3 months' follow-up and increased to 69.84% at 12-month follow-up, surpassing the rate at 3-month follow-up (p < 0.001). The LSIL regression rate was 75.85% at 3 months' follow-up and rose to 86.77% at 12-month follow-up, exceeding the rate at 3-months' follow-up (p < 0.001). Multivariate analysis revealed that single HPV infection (OR 2.296 [95%CI 1.550-3.402]) was an independent predictor of HPV remission after 5-ALA PDT treatment. Single HPV infection (OR 1.690 [95% CI 1.077-2.652]), type III transformation zone (OR 3.094 [95% CI 1.899-5.041]), HPV remission after PDT treatment (OR 4.938 [95% CI 3.099-7.870]) were independent predictors of LSIL participants receiving total lesion regression after PDT treatment. Adverse reactions were all mild. 5-ALA PDT is an effective and non-invasive therapy for LSIL patients with HR-HPV infection. Identifying predictors of treatment success may optimize patient selection, ultimately improving clinical outcomes.

Our descriptive study focused on morphologic characteristics of hyperchromatic crowded groups (HCGs) in ThinPrep cervical cytology tests when reviewed with the artificial intelligence (AI)-assisted Hologic Genius Digital Diagnostics System (HGDDS). After IRB approval, our archives were searched over a 1-year period for potential HCGs. A total of 157 slides with HCGs were selected, scanned, and analyzed using the HGDDS. One cytologist and one cytopathologist interpreted these cases while enumerating the cytomorphologic characteristics as seen with the HGDDS. Of the 157 cases, a total of 84.7% were called Negative for Intraepithelial Lesion or Malignancy (NILM) on original ThinPrep interpretation (OTPI) as opposed to 76.4% with HGDDS. 5.7% and 3.2% of the cases were called high-grade squamous intraepithelial lesion (HSIL) and atypical glandular cells (AGC) on OTPI, as compared to 4.5% and 8.3% on HGDDS. 6.4% of cases were interpreted as adenocarcinoma on both OTPI and HGDDS. A total of 16 cases were called NILM-Atrophy by both modalities. Concordance for pathologist diagnosis between HGDDS and OTPI for 157 cases was 0.610 (kappa value). For 25 cases, there was a follow-up biopsy diagnosis, including 10 cases of adenocarcinoma, 5 of Cervical Intraepithelial Neoplasia (CIN) 2-3, and 1 case of CIN 1. The sensitivity, specificity, positive predictive value, and negative predictive value for the detection of CIN2+ lesions, when ASC-H/AGC and above were considered, were 100%, 50%, 75%, and 100%, respectively. Our initial study shows encouraging results in the evaluation of HCGs presented as two-dimensional static images on a computer monitor by the HGDDS.

Female genital tract lesions with putative prostatic differentiation include vaginal tubulosquamous polyp (TSP), cervical ectopic prostatic tissue (EPT), and adenoid basal carcinoma (ABC). HoxB13 is a transcription factor specific for the prostate, not previously assessed in these lesions. A cohort of 13 TSPs, 6 EPTs, 17 ABCs, and 8 adenoid basal hyperplasia (ABH) was analyzed for expression of prostatic markers HoxB13, NKX3.1, p16, and androgen receptor (AR). Additional 28 cervical high-grade squamous intraepithelial lesions (HSILs), 21 cervical squamous cell carcinomas (SCCs), 19 endocervical adenocarcinomas (EACs), and 10 endometrial endometrioid adenocarcinomas (ECs) were included. The results were recorded as immunoreactive score (IRS). In TSPs and EPTs, HoxB13 and NKX3.1 were positive in 100% and 89.5% of cases, respectively. No HoxB13, NKX3.1, and p16 was observed in ABHs. In contrast, all ABCs showed diffuse p16 positivity. NKX3.1 was positive in 82.6% of ABCs (median IRS = 2), HoxB13 was positive in 100% of ABCs (median IRS = 8), and the difference was statistically significant (p < 0.001). Both HoxB13 and NKX3.1 were positive in 9.5% (2/21) SCCs and 21.1% (4/19) EACs. Additionally, 40% (4/10) ECs were HoxB13-positive (IRS = 1-2). Any positivity of HoxB13 was 80% specific and 100% sensitive for the ABC. NKX3.1 was only 82.4% sensitive, but 88% specific for the diagnosis of ABC. Additionally, HoxB13 was also seen in 29.8% HSILs. No ABC showed AR positivity, while this was observed in rare cells (IRS 1-2) in 30.8%, 16.6%, and 37.5% of TSCs, EPTs, and ABHs, respectively. HoxB13 can be a useful and reliable marker for identification of TSPs, EPTs and ABCs.

High-risk human papillomavirus (hrHPV) infection is the primary cause of cervical cancer. However, hrHPV testing lacks specificity in detecting neoplastic changes. This study explored the utility of quantitative methylated HPV DNA markers for precise detection of cervical lesions. Using hybridization capture-based bisulfite sequencing, we analyzed genome-wide HPV methylation patterns. The study included a training cohort of 60 cervical exfoliated cell samples and a validation cohort of 29 samples. Analysis of 112 CpG sites across the HPV genome revealed that genome-wide HPV16 methylation levels correlated with disease progression. Squamous cell carcinoma (SCC) showed 1.4-fold higher methylation levels compared to normal tissue (p = 0.0032). Progressive methylation increases in the E5-α and L2 genes were observed across the spectrum of cervical lesion severity, from normal tissue through high-grade squamous intraepithelial lesion (HSIL) to SCC. Intersection analysis of differentially methylated CpG sites between HSIL vs Normal and SCC vs Normal identified 16 consistently hypermethylated CpG sites in the E5-α, E7, L2, and L1 genes, distinguishing both HSIL and SCC from normal tissue. This pilot study identifies a five-CpG methylation panel (E5-α_3887, E5-α_3941, E7_701, L2_4441, and L2_5128) as promising triage biomarkers for HPV16-positive women, achieving high discriminatory performance (AUC = 0.919 in a validation cohort) for detecting cervical lesions. This genome-wide capture sequencing identified novel HPV16 methylation markers that distinguish cervical lesions from normal tissue, supporting the feasibility of HPV methylation-based triage for HPV-positive women in cervical cancer screening.

Penile squamous cell carcinoma (SSC) accounts for almost 10% of male cancers in high-incidence areas, although the incidence in Europe is below 1%. About half of penile SCCs arise from a precancerous high-grade squamous intraepithelial lesion (HSIL) caused by atransforming infection with human papillomavirus (HPV), most often high-risk HPV16. The HPV E6/E7 oncoproteins bind to proteins of the p53 and retinoblastoma pathways. This cell cycle disruption results in cellular accumulation/overexpression of p16, which serves as surrogate biomarker for HPV-associated carcinogenesis. The majority of HPV-independent SCCs arise in lesions of lichenoid dermatoses (lichen sclerosus and lichen planus) via rapidly progressing precancerous differentiated penile intraepithelial neoplasms (d-PeIN). These inflammation-associated, generally highly differentiated keratinized lesions commonly carry mutations in the tumor suppressor genes TP53 and CDKN2A. Missense TP53 mutations lead to accumulation of p53/agerrant p53 in the nuclei of proliferating tumor cells (nuclear overexpression), which serves as a surrogate marker for aTP53 missense mutation. About one third of HPV-independent penile SCCs arise in the absence of dermatoses and mutations in tumor suppressor genes and lack p16 and p53 overexpression. They arise via verrucous/verruciform PeIN. Correct identification of the etiology of precursor lesions is of clinical significance, as HPV-associated SCCs have better prognoses and survival rates. Moreover, the etiology is particularly relevant to the choice of treatment for the precancerous lesion. The slow progression of HSIL to invasive cancers allows time-intense surgical, destructive, or drug-based treatment options. In contrast, the precursor lesion of dermatoses-associated SCC, d‑PeIN, calls for immediate surgical resection to exclude early invasion. Guideline-conform treatment of lichenoid dermatoses reduces the cancer risk.

Introduction: Cervical cancer (CC) remains a significant global health burden, primarily driven by persistent high-risk human papillomavirus (HPV) infection. While HPV is the necessary cause, the role of host reproductive cofactors, such as early menarche, in promoting carcinogenesis remains controversial. This systematic review synthesizes the epidemiological evidence on the association between early menarcheal age and the risk of cervical cancer and its precursors. Methods: This review was conducted adhering to the PRISMA 2020 guidelines. A systematic search of PubMed, EMBASE, and Web of Science was performed to identify observational (cohort and case-control) studies published to date. Studies assessing the risk of invasive cervical cancer (ICC), cervical intraepithelial neoplasia (CIN/HSIL), or high-risk HPV (HR-HPV) infection in relation to menarcheal age were included. The methodological quality and risk of bias for included non-randomized studies were rigorously assessed using the Risk Of Bias In Non-randomized Studies - of Interventions (ROBINS-I) tool. Results: Seventeen studies met the inclusion criteria. A subset of case-control and cross-sectional studies reported a statistically significant positive association between early menarche and cervical disease. Notably, one meta-analysis of Chinese studies reported a pooled Odds Ratio (OR) of 3.242 for ICC. Another study found a strong association between early menarche (&lt;13 years) and HPV 16/18 infection (OR = 6.2). A 2023 study also identified early menarche as a significant risk factor for high-grade squamous intraepithelial lesions (HSIL). However, these findings are contradicted by larger, more methodologically robust prospective cohort and pooled case-control analyses. These high-quality studies, which included comprehensive adjustment for key confounders, found no significant independent association between menarcheal age and risk of ICC. The evidence demonstrates that the observed association is strongly mediated by age at first sexual intercourse (AFSI), which is significantly predicted by early menarche (e.g., OR = 6.4). Discussion: The data highlights a critical epidemiological challenge in distinguishing between behavioral mediation and biological causation. The findings are evaluated through two primary pathways: 1) The behavioral-mediation pathway, where early menarche serves as a robust proxy for early AFSI and subsequent HPV exposure; and 2) The biological-plausibility pathway, which posits that early endogenous estrogen exposure creates a "window of vulnerability" in the cervical transformation zone, increasing susceptibility to HPV. The robust null findings in studies that control for AFSI, alongside recent data distinguishing risk for uterine (significant) versus cervical (null) cancer, strongly support the behavioral-mediation pathway. Conclusion: While several studies report a significant positive association, the weight of the highest-quality epidemiological evidence suggests that early menarche is not a direct, independent causal factor for cervical cancer. Instead, it functions as a significant indirect risk marker. The association is robustly and almost entirely mediated by the strong correlation between early menarche and early sexual debut. Public health interventions should therefore focus on this behavioral link, targeting education and HPV vaccination to adolescents, particularly those undergoing early pubertal maturation.

Noninvasive follicular thyroid neoplasia with papillary-like nuclear characteristics (NIFTP) is characterised by an indolent behaviour and was defined in 2016 to avoid overtreatment in differentiated thyroid cancer (DTC). To report the clinicopathological characteristics and outcomes of patients with NIFTP treated at a Chilean centre between 2016 and 2023. Observational retrospective study. Of 1103 patients with thyroid neoplasia treated with surgery, 104 (9.42%) had NIFTP. Clinicopathological variables were recorded, including ultrasound characteristics, fine-needle aspiration biopsy (FNAB) results, genetic testing when available, type of surgery, tumour size, and follow-up data. Of 104 patients, 85 (81.7%) were female, age of 44 ± 14.2 years and a median tumour size of 1.7 cm (range 0.1-7.1). Eighty-six (82.7%) had available preoperative staging ultrasound: 1 (1.2%), 39 (45.3%), 38 (44.2%), and 8 (9.3%) were ACR-TIRADS 2, 3, 4, and 5, respectively. Sixteen (15%) NIFTP were incidental, which were smaller than non-incidental NIFTP (median 0.4 cm (0.1-2.2) vs. 1.9 cm (0.6-7.1), p < 0.001). Of the 86 FNAB results available, 2 (2.3%), 10 (11.6%), 20 (23.3%), 24 (27.9%), and 30 (34.9%) were Bethesda I, II, III, IV, and V, respectively. Forty-three patients (41.3%) were treated with lobectomy, 58 (55.8%) with total thyroidectomy (TT), and only 3 (2.9%) with TT and lymph node dissection. In Bethesda II patients, surgery was indicated in cases of nodule growth, showing a larger tumour size than other Bethesda categories (3.0 ± 1.4 vs. 1.8 ± 1.02 cm, p = 0.015). ThyroidPrint® was performed in 12 patients with Bethesda III or IV, resulting suspicious in 11 (92%): of these, 8 (67%) underwent lobectomy. There were no significant differences between lobectomy and TT regarding sex, ACR-TIRADS, tumour size, or ThyroidPrint® results. Twelve (11.5%) were multifocal and 5 (4.8%) bilateral. Fifty-two patients (54%) were followed for ≥ 1 year using follow-up criteria and response to treatment for low-risk DTC recurrence. Thirty-four (65%) had excellent response, 15 (28.8%) indeterminate (13 (25%) by biochemical criteria and 2 (3.8%) by ultrasound), 3 (5.7%) incomplete biochemical (2 (3.8%) due to elevated Tg and 1 (1.9%) due to elevated anti-Tg antibodies), and none with incomplete structural response. There were no differences between lobectomy and TT ± lymph node dissection regarding the type of response. At the end of the follow-up, there were no deaths, and no new interventions were required due to recurrence. In this series, NIFTP showed indolent behaviour and excellent prognosis. Ultrasonographically, 90% presented as ACR-TIRADS 3 or 4, with less than 10% as ACR-TIRADS 5. Regarding FNAB, nearly half were indeterminate, one-third were Bethesda V, and none Bethesda VI. No significant differences in clinical outcomes were found between lobectomy and TT.

Evaluating Thyroid Lesions Using Fine-Needle Aspiration Cytology and the Bethesda System: Insights From a Tertiary Care Hospital

To develop Australian anal cancer screening guidelines for people living with HIV. In 2023, ASHM Health assembled a committee to create guidelines, based on existing international guidelines and utilizing data from the Study of the Prevention of Anal Cancer (SPANC). SPANC provided Australian-specific data on different screening methodologies for the detection of anal high-grade squamous intraepithelial lesions. The guidelines were released in March 2025. They recommend primary high-risk human papillomavirus (HRHPV) testing with cytology triage for high-resolution anoscopy. Gay, bisexual and other men who have sex with men (GBM) and trans-women living with HIV should be offered screening from 35 years of age. Cis-women, trans-men and other cis-men (not GBM) living with HIV should be offered screening from 45 years of age. All anal cancer screening should include annual digital ano-rectal examination, examination of the peri-anal region and a thorough medical history. Screening should be repeated every 3 years for those who screen negative. Screening should be discontinued, with shared decision-making, at age 75 years and/or in individuals with two consecutive negative screening visits who are not currently sexually active. These are the first guidelines to recommend primary HRHPV testing with cytology triage as the screening modality. They will assist clinicians in identifying and screening people living with HIV at higher risk of anal cancer and will enable screening and referral of people living with HIV at highest risk for high-resolution anoscopy, while screening and treatment services capacity are expanded in Australia.

ImportanceChatGPT has emerged as a medical resource through advanced language processing. Patients with thyroid nodules classified under The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) may use it to complement discussions with physicians.ObjectiveWe aimed to determine whether ChatGPT's recommendations on managing thyroid nodules classified by TBSRTC align with those of experienced thyroid specialists.Setting/ParticipantsA multidisciplinary panel of 5 thyroid cancer specialists, including otolaryngologists and endocrinologists, from 3 university-affiliated teaching hospitals in Montreal, Canada, evaluated the responses.Intervention/ExposureChatGPT-3.5 was prompted with 4 questions for each of the 6 Bethesda categories regarding the meaning and management of thyroid nodules, generating 24 responses for evaluation.Main Outcome/MeasuresWe assessed ChatGPT’s accuracy against the latest American Thyroid Association (ATA) guidelines using a 4-point Likert scale (<50%, 50-74%, 75-89%, >90%). Additionally, specialists rated their comfort or reluctance in recommending ChatGPT as a complementary tool for patient discussions.ResultsOf the 24 ChatGPT-generated responses, 19 (79.2%) demonstrated moderate to good consistency with the ATA guidelines. The mean consistency score was 3.38/4 and median was 3.5. Consensus (IQR ≤ 1) was achieved in 23 out of 24 responses (95.8%), reflecting strong inter-rater reliability. Consistency scores were highest in Bethesda I–III and declined progressively in higher-risk categories, with the lowest mean score observed in Bethesda VI. Similarly, an upward trend in clinician reluctance was observed from Bethesda I through VI, indicating greater caution in recommending ChatGPT responses for patients suspicious for or diagnosed with malignancy (Bethesda V–VI).Conclusion and RelevanceWhile ChatGPT’s responses generally align with specialist recommendations, they are not fully reliable. ChatGPT lacks the ability to serve as an independent or accurate source of medical advice for thyroid nodule management. It remains a useful complement for patient discussions, especially in low-risk scenarios, but further improvements are necessary to make it a safe, reliable component of patient care in complex cases.

Background: Thyroidectomy is a frequently performed operation used to treat benign and potentially hazardous thyroid-related disorders. Even though it functions properly, there is a likelihood that it will cause substantial issues. The objective of the research was to investigate at the explanations, rates of complications, and linkages between these incidents at a Jordanian tertiary care centre. Methods: We examined 152 patients who experienced a thyroidectomy between January 2022 and May 2025 as part of a former cohort study. We gathered statistics about the patients' ages, genders, the type of surgery (hemithyroidectomy vs. total thyroidectomy), the specifics of the surgery, and any complications encountered afterward. Complications have been identified as hypocalcaemia (calcium levels below 8.0 mg/dL) or symptoms and recurrent laryngeal nerve (RLN) damage that was demonstrated by laryngoscopy. Descriptive statistics, chi-square tests, and t-tests were used in statistical research. Results: The population's median ages were 45.2±14.1 years, and 84.2% of them were women. The predominant rationale (61.8%) was a benign disease, with multinodular goitre (27.6%) and follicular adenoma (22.4%) coming in first and second, respectively. 38.2% of the samples were found to be cancerous, with papillary thyroid carcinoma being the most common type. From 30% (Category III) to 100% (Category VI) (p&lt;0.001), the Bethesda System for cytology had a strong positive projection value for cancer. 32% of people who had the surgery ended up with an adverse outcome, with hypocalcaemia being the most prevalent (32%). There was a 38% higher rate of hypocalcaemia after a total thyroidectomy, compared to a 12% rate after a hemithyroidectomy (p&lt;0.001). Diabetes mellitus has been demonstrated to be a major comorbidity-based risk factor for low calcium levels (43%, p&lt;0.01). There was an important correlation between the manner of surgery and the reason for it. The total thyroidectomy group had a much higher rate of cancer (55.4%) compared to the other group (21.8%) (p&lt;0.001). Conclusion: The vast majority of those in our local area have a thyroidectomy for ordinary disease, but many of them have a thyroidectomy for a malignant disease. Hypocalcaemia is the main problem, and it is highly related to undergoing a total thyroidectomy and diabetes. These results show how important it is to properly plan and carry out surgery, and they provide surgeons crucial details for consulting to patients before surgery and figuring out their risks.

Recent studies have found the presence of post- hysterectomy atypical glandular cells in upper vagina in ~ 30% patients of Endometrial Cancer (EC) with implications of causing isolated vaginal recurrence. The primary objective was to determine the effectiveness of cervical canal and fallopian tube occlusion in preventing intra-operative tumour spillage in EC. A Prospective Interventional Single Institutional pilot study with random allocation to two arms using computer- generated random number sequence was conducted between January 2022 to Feb 2023. Patients with histologically confirmed epithelial endometrial cancer, including endometrioid carcinoma, papillary serous, clear-cell, squamous, mucinous, undifferentiated, and carcino-sarcoma with surgery as primary definitive treatment modality were included. Spillage was detected using vaginal smear and peritoneal wash cytology taken pre- and post- hysterectomy. In interventional arm, cervical os and fallopian tube were occluded using silk sutures as additional steps during surgery. Rate of negative to positive conversion of vaginal smear and peritoneal wash cytology obtained before and after hysterectomy in the interventional arm was compared with control arm who underwent surgery with standard surgical steps. Out of 33 eligibile patients, 3 were excluded due to double primaries and history of radiation pelvis. The two arms of 15 patients each were comparable with respect to clinico-pathological characteristics. The most common histology, grade, degree of myometrial invasion, LVSI, stage, and mean tumour diameter was endometrioid variety (100%), low-grade (83.3%), & >1/2 (50%), negative (83.3%), 1A (41.7%), and 4cm in interventional arm and endometrioid (100%), low grade (76.9%), >1/2 (84.6%), negative (92.3%), 1B (84.6%), and 4.5cm in non- interventional arm respectively. None of the patient in either arm had negative to positive conversion of vaginal and/or peritoneal cytology. We observed no difference of cervical and tubal occlusion on tumour cell spillage in EC. CTRI/2022/05/042348.

Women Living with HIV (WLHIV) are at increased risk of persistent high-risk Human Papillomavirus (HR-HPV) infections and cervical cancer. However, data on HPV genotype distribution and cervical cytologic abnormalities remain limited in North Africa, particularly among women receiving effective antiretroviral therapy (ART). To assess the frequency of cytologic abnormalities in WLHIV in Sétif, Algeria, identify HR-HPV genotypes, and evaluate associated immunovirological factors. A cross-sectional study was conducted from January to December 2024 at the HIV/STI/AIDS Reference Center in Sétif. WLHIV aged ≥ 18 years who provided informed consent were included. Each participant underwent a gynecological examination, cervical cytology (Pap smear), HR-HPV genotyping by molecular biology, and immunovirological assessment (CD4 T-cell count, HIV viral load). Colposcopy and biopsy were performed when indicated. Among 115 enrolled participants, 100 smears were interpretable. Cytologic abnormalities : Atypical Squamous Cells of Undetermined Significance (ASC-US), Low-Grade/High-Grade Squamous Intraepithelial Lesions LSIL, HSIL) were found in 28% of WLHIV. HR-HPV infection was detected in 32% of participants, mainly genotypes HPV52, HPV16, and HPV18. A significant association was observed between HR-HPV positivity and high-grade lesions (HSIL) (p = 0.018; OR = 9.57, 95% CI: 1.02-89.48). WLHIV in Algeria show a high prevalence of HPV-related cytologic abnormalities, even with adequate immune status and viral suppression. These findings emphasize the importance of regular cervical screening and support current global recommendations for comprehensive prevention strategies, including HPV testing and vaccination.

PurposeThis study aims to investigate the relationship between inflammatory-immune cells and ≥high-grade squamous intraepithelial lesions (HSIL), and to clarify the role of immune-inflammatory cells mediating human papilloma virus (HPV) and ≥HSIL.MethodsWe retrospectively enrolled 427 patients with ≥HSIL and 357 ≤low-grade squamous intraepithelial lesions (LSIL) from June 1, 2013 to June 1, 2023. Clinical data such as age, peripheral blood inflammatory-immune cells, serum tumor markers, HPV infection status were collected to evaluate the relationship between clinical indicators and ≥HSIL mediated by inflammatory-immune cells.ResultsCompared with the ≤LSIL cohort, the patients with ≥HSIL exhibited a significantly higher prevalence of infection with ≥2 type HPV genotypes compared to those with a single HPV infection (34.55% vs 17.65%, p = 0.045). Multiple HPV infection and lower CD4/CD8 ratio were the independent risk factors for the patients with ≥HSIL besides HPV infection. Moreover, the top three HPV genotypes were HPV-16, HPV-18 and HPV-52 among the populations of ≥HSIL. Interestingly, HPV (1.29%), HPV-16 (2.48%) and HPV-52 (9.70%) infection were partially mediated by CD4/CD8 ratio to promote ≥HSIL (p < 0.05). Furthermore, compared with the HSIL cohort, SCC, HPV16, HPV52 infection and higher neutrophil and lymphocyte ratio (NLR) were the independent risk factors for cervical cancer (CC). Among women with CC, the top three HPV types are 16, 18, and 52. The relationship between HPV/HPV-16 and CC was partially mediated by the NLR, with mediation effect ratios of 1.87% and 2.85%, respectively (p < 0.05).ConclusionHPV-induced HSIL and CC are associated with immune-inflammatory status. Specifically, the CD4/CD8 ratio plays a significant mediating role during the HSIL stage, whereas NLR assumes a major mediating role in the CC stage. Thus, immune-inflammatory cells play distinct roles at different stages of CC progression.

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

To investigate the frequency of micronuclei (MN) and binucleated (BN) cells in thyroid nodules and adjacent normal tissue, and evaluate their correlation with cytological (Bethesda classification) and histopathological diagnoses to assess their potential utility in preoperative malignancy prediction. This prospective study included 39 patients (16 benign, 19 papillary carcinoma, 4 follicular carcinoma) who underwent thyroidectomy. Tissue samples from both nodular and adjacent normal thyroid regions were collected. MN and BN frequencies were evaluated in 1000 cells per sample using May-Grünwald and 5% Giemsa staining. Data were analyzed in relation to Bethesda categories and final surgical pathology using mixed-effects models in R 4.4.1. ROC analysis was conducted to assess the diagnostic performance of MN/BN frequency. MN and BN frequencies were significantly higher in nodular tissue compared to adjacent normal thyroid tissue (p < 0.05). Malignant lesions showed significantly increased MN/BN frequencies compared to benign ones, although no significant difference was observed between papillary and follicular subtypes (p < 0.05). MN/BN frequencies were also significantly higher in Bethesda categories III-VI compared to categories I-II (p < 0.05). No significant variation was found in normal thyroid tissue across cytological or pathological groups. MN and BN cell frequencies were elevated in malignant nodules and higher Bethesda categories, supporting their potential role as adjunctive cytogenetic markers in thyroid nodule assessment. While findings are promising, their diagnostic utility in indeterminate nodules remains unclear. Larger, FNAB-based studies are required to validate their feasibility and clinical relevance in routine preoperative evaluation.

Objectives Limited data are available regarding the clinical characteristics and treatment outcomes of cervical HSIL in women under 25, particularly in Asian populations. This study aimed to investigate the clinical features of cervical HSIL in women under 25 and to compare the efficacy of various treatment modalities, with the goal of informing early detection and optimal management strategies. Methods A retrospective cohort study was conducted involving 210 patients under 25 who were diagnosed with cervical HSIL at Obstetrics and Gynecology Hospital of Fudan University between January 2019 and December 2021. Data on clinical features, cytology, HPV status, colposcopy findings, and treatment approaches were collected and analyzed. Treatment outcomes were assessed by comparing postoperative cytology, HPV clearance, and pathological results at 6 and 12 months among patients managed with observation, CO2 laser therapy, or LEEP. Results Most patients (89.0%) were diagnosed via routine screening and 86.7% were asymptomatic. Among symptomatic cases, postcoital bleeding (10.0%) and abnormal vaginal discharge (3.3%) were reported. Cytology showed NILM in 38.1%, ASCUS 30.5%, LSIL 21.0%, HSIL 7.1%, and ASC-H 3.3%. HPV was detected in 98.1% of patients, predominantly HPV16 (65.2%). Cytology alone showed low sensitivity for detecting cervical HSIL (7.1%) compared with HPV testing (98.1%) or co-testing (98.6%, χ²=534.468, P&amp;lt;0.001). At 12-month follow-up, the LEEP group exhibited the highest rates of normal cytology (90.5%), HPV clearance (87.5%), and histologic cure (95.2%), outperforming both the laser and observation groups. Multivariate logistic regression analyses identified reproductive tract inflammation as an independent risk factor for persistent high-risk HPV infection among patients undergoing observation. Conclusions Most cervical HSIL under 25 are asymptomatic. Cytology alone is insufficient for reliable detection, HPV based screening significantly improves sensitivity. Among treatment strategies, LEEP offers the most effective histological cure rate, although potential reproductive risks warrant careful consideration in nulliparous women.

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 &gt; 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.

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 &lt; 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.

Thyroid lesions are a common finding, especially in the adult population, based on the evidence that more than 50% of individuals have thyroid nodules. The increasing detection of these lesions is mostly due to frequent ultrasonographic head and neck evaluation, which can now identify small subcentimeter nodules. Fortunately, most of these nodules are benign (70%), with only 5-10% of them attributed as malignant lesions. However, the remaining 20% falling into the category of indeterminate lesions which can lead to some pitfalls and tricky evaluations. Since 1996, different classification systems have been introduced and among them, the most worldwide adopted is the Bethesda System for Reporting Thyroid Cytopathology (TBSRTC). It is well-known that TBSRTC as well as other classification systems, subclassified indeterminate lesions into subgroups which specifically for the TBSRTC include a) atypia of undetermined significance (AUS), b) follicular or oncocytic cell neoplasm (FN) and c) suspicious for malignancy (SFM). However, despite the high positive predictive value (97%-99%), sensitivity (65%-99%) and specificity (72%-100%) of thyroid FNAC, diagnostic pitfalls exist that can lead to false positive and/or false negative results. This inconvenience is mostly due to the overlapping of morphological features in terms of cells and even background. This review discusses the most important potential pitfalls in the cytologic evaluation of thyroid lesions that can lead to such diagnostic errors.