Background: Cervical intraepithelial neoplasia grade 2 (CIN2) represents a controversial lesion in cervical cancer prevention. Traditionally included in the aggregate CIN2+ endpoint for reasons of diagnostic stability and statistical power, isolated CIN2 has unique biological characteristics: greater interobserver variability, a high probability of spontaneous regression and a lower risk of progression compared to CIN3. Objectives: To critically describe the epidemiology, natural history and management strategies of CIN2, integrating data from clinical and population-based studies and comparing the recommendations of the main international guidelines. Methods: A narrative review was conducted using a search of PubMed and Scopus (1990–January 2025). Prospective and retrospective studies on isolated CIN2, screening and vaccination trials with CIN2+ endpoints, biomarker research, and consensus documents (ASCCP, ESGO, GISCi, Ministry of Health, WHO) were included. Results: Clinical studies have shown a high probability of CIN2 regression (50–70% within two years, >70% in those <25 years), compared to a 10–15% risk of progression, especially in the presence of persistent HPV16. Screening trials and vaccine evaluations with CIN2+ endpoints have documented the efficacy of the HPV test and a dramatic reduction in lesions in vaccinated cohorts, which was also confirmed for isolated CIN2. The most recent guidelines have progressively adopted a risk-based approach, which allows for active surveillance in young women or those seeking to conceive, while the WHO maintains a screen-and-treat model in resource-limited countries. Conclusions: CIN2 is not a lesion to be treated automatically, but rather a paradigmatic model for personalized management. Integrating epidemiological and clinical data, supported by biomarkers, allows for reducing overtreatment without compromising oncological safety.

Background and Objectives: Human papillomavirus (HPV) is the most prevalent sexually transmitted infection worldwide and, beyond its oncogenic potential, may impair reproductive health in both sexes. This review examines HPV’s effects on male and female fertility, obstetric outcomes, vertical transmission, and fertility-sparing management in oncology. Materials and Methods: A systematic search of PubMed, Embase, and Scopus was conducted using terms related to HPV and reproduction. Additional search terms included those related to therapeutic vaccines, antivirals, and genotype prevalence. English-language human studies reporting clinical reproductive outcomes were included. Thirty-seven studies met the inclusion criteria. Two reviewers independently screened and assessed study quality using a simplified GRADE framework. Results: In men, seminal HPV infection correlates with reduced progressive motility (SMD ≈ −0.85), abnormal morphology, and increased DNA fragmentation. In women, high-risk HPV doubles the odds of infertility (OR ≈ 2.3) and is associated with endometrial involvement. High first-trimester viral load predicts vertical transmission (aOR 6.4), which is also increased by vaginal delivery (RR 1.8) and is linked to PROM (OR 1.8) and preterm birth (OR 1.8). Modeling suggests that nine-valent vaccination plus 5-year HPV-based screening could reduce CIN2+ by up to 80% and excisional treatments by >75%. Fertility-sparing surgery in early cervical cancer yields a <4% recurrence and up to 68% live birth rates. Conclusions: This review uniquely synthesizes reproductive and oncologic impacts of HPV and emphasizes risk stratification, multidisciplinary prevention, and fertility preservation. Integration of HPV DNA quantification, personalized care, and vaccine-based strategies offers a path toward optimized outcomes in both sexes.

Background/Objectives: Cervical cancer is mainly driven by persistent infection with high-risk human papillomaviruses (HPV), particularly HPV16 and HPV18. Despite advances in cytology, HPV-DNA testing and vaccination, challenges remain in the triage of HPV-positive individuals, prognostic stratification and prediction of treatment response. Non-coding RNAs (ncRNAs), including microRNAs, long non-coding RNAs and circular RNAs, together with host genetic factors influencing ncRNA expression and emerging lncRNA-encoded peptides, are increasingly recognized as regulators of HPV-associated carcinogenesis. This review summarizes their biological and potential clinical relevance. Methods: A structured literature search was conducted in PubMed and Scopus. Eligible studies included experimental, clinical, observational, genomic and translational investigations on ncRNA dysregulation, circulating or exosomal ncRNAs, treatment-response signatures, host genetic variation and lncRNA-encoded peptides in HPV-associated cervical precancer and cancer. Results: HPV oncoproteins can reshape host ncRNA networks through transcriptional and epigenetic mechanisms. Several miRNAs, lncRNAs and circRNAs are involved in cell-cycle control, apoptosis, senescence, epithelial–mesenchymal transition, immune regulation, DNA repair and treatment resistance. Circulating, exosomal and urinary ncRNA signatures have shown diagnostic or prognostic potential in exploratory cohorts. Specific lncRNAs, including ENSG00000267838/lnc-LENG9-5 and lncRNA-EME1, have been associated with chemoradiotherapy response and radioresistance. The lncRNA-encoded peptide TUBORF represents a novel preclinical therapeutic candidate, while genetic variation may further modulate lncRNA function in HPV-related cervical cancer. Conclusions: ncRNAs are promising candidates for risk stratification, non-invasive diagnosis, treatment-response prediction and therapeutic development in HPV-associated cervical disease. However, evidence remains exploratory, requiring prospective multicentre validation and standardized workflows before clinical implementation.

Deep endometriosis (DE) frequently affects pelvic organs and may impair urinary function through both direct involvement and surgical nerve disruption. Minimally invasive excision is the standard treatment for symptomatic DE, but its impact on lower urinary tract symptoms (LUTS) remains uncertain. We conducted a systematic review according to PRISMA 2020 guidelines to evaluate postoperative urogynecological outcomes following laparoscopic or robotic surgery for DE (PROSPERO ID: CRD420251113885). PubMed, Scopus, and the Cochrane Library were searched for studies published over the last 25 years. Eligible studies included women undergoing minimally invasive surgery for DE with postoperative urinary outcomes assessed by validated questionnaires or urodynamic testing. Methodological quality was appraised using the Newcastle–Ottawa Scale. Out of 175 records, 9 studies involving 20– 289 participants met the inclusion criteria. Six studies reported significant postoperative improvements, particularly in urgency, frequency, and dysuria, with benefits most evident in women presenting with moderate-to-severe preoperative LUTS. Improvements were observed in both subjective assessments, by using standardized questionnaires such as the International Consultation on Incontinence Questionnaire (ICIQ), Urinary Symptom Profile (USP), International Prostate Symptom Score (IPSS), and Visual Analogue Scale (VAS), and, in some cases, objective measures such as bladder capacity and uroflowmetry. Conversely, three studies documented no significant change or worsening of urinary function, predominantly in women with minimal baseline dysfunction or extensive parametrial and sacral nerve involvement. In these series, postoperative deterioration included increased voiding difficulties and worsening symptom scores. Across studies, outcome definitions, assessment tools, surgical techniques, and follow-up intervals varied substantially, introducing significant heterogeneity that prevented a formal meta-analysis from being performed. Overall, minimally invasive surgery for DE may yield meaningful symptomatic relief in selected patients, particularly when nerve-sparing techniques are applied. However, functional deterioration remains a relevant risk, especially among those with minimal baseline LUTS. Future research should prioritize prospective trials with standardized outcome measures, longer follow-up, and stratification by preoperative symptom burden to optimize patient selection and refine surgical approaches.

In postmenopausal women with high-grade cervical intraepithelial neoplasia (CIN3), hysterectomy is frequently performed after loop electrosurgical excision procedure (LEEP) due to the concern for residual disease or occult carcinoma. However, the decision to proceed with hysterectomy is often made without validated predictive criteria, increasing the risk of overtreatment or underdiagnosis. The aim of this study is to identify independent predictors of residual CIN2+ (CIN2, CIN3, adenocarcinoma in situ, invasive carcinoma) or invasive disease in hysterectomy specimens following LEEP in this high-risk population. Methods: We conducted a multicenter retrospective study including 154 postmenopausal women (aged 50–75) who underwent total hysterectomy within 12 months after LEEP for histologically confirmed CIN3. Data collected included human papillomavirus (HPV) genotyping (pre- and post-LEEP), endocervical curettage (ECC), cone margin status, transformation zone type, and histopathological outcomes of the hysterectomy specimen. Logistic regression and ROC curve analysis were used to assess predictive factors. Results: Residual disease (CIN2+, AIS, or carcinoma) was found in 38 patients (24.7%), including 7 cases (4.5%) of occult carcinoma. Persistent high-risk HPV post-LEEP was the strongest independent predictor (adjusted OR for HPV 16/18: 74.0; p < 0.001), followed by positive ECC (OR: 3.64; p = 0.028). Cone margin status was not independently associated. The multivariate model showed good discriminative performance (AUC = 0.860; sensitivity 67.2%, specificity 72.8%). Conclusions: Our findings suggest that persistent high-risk HPV infection and positive ECC are reliable predictors of residual or occult disease. These markers should be integrated into post-LEEP follow-up protocols to better identify candidates for hysterectomy and minimize unnecessary surgeries.

Background/Objectives: Sacrospinous ligament fixation (SSLF) is a well-established native tissue vaginal procedure for uterine/vault prolapse. Despite favorable success rates, the procedure presents technical challenges due to the deep operative field and proximity to critical neurovascular structures. To review current evidence regarding anatomical considerations, surgical technique, fixation strategies, suture materials, device-assisted methods, and perioperative complications in SSLF. Methods: A structured narrative review of the contemporary literature was conducted, focusing on comparative and systematic studies evaluating unilateral versus bilateral fixation, anterior versus posterior approach, suture type and number, and suture-capturing or anchor-based devices. Anatomical, functional, and safety outcomes were critically analyzed. Results: SSLF achieves favorable anatomical success rates with significant symptom improvement. Meticulous knowledge of sacrospinous ligament anatomy is critical to reduce bleeding and neuropathic complications. Unilateral fixation remains the most common technique, while bilateral fixation may benefit selected patients. According to the available evidence, the anterior approach may better preserve vaginal length, although it may be associated with longer operative time and short-term urinary morbidity. Absorbable and permanent sutures appear to provide comparable anatomical durability, while placement of two sutures remains the most commonly used fixation strategy. Device-assisted techniques may facilitate suture placement but require advanced anatomical expertise. Conclusions: SSLF is a safe and effective suspension procedure when individualized and meticulously performed. Further randomized studies evaluating long-term anatomical and patient-reported outcomes are warranted.