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: Locally advanced cervical cancer (LACC) represents a significant challenge in oncology, requiring accurate assessment of local extent and metastatic spread. Multiparametric magnetic resonance imaging (mpMRI) has assumed a central role in the loco-regional characterization of the tumor due to its high soft-tissue resolution and the ability to integrate functional information. Objectives: In this narrative review, we explore the use of mpMRI in the diagnosis, staging, and treatment response of LACC, comparing its performance with that of PET/CT, which remains complementary for remote staging. The potential of whole-body magnetic resonance imaging (WB-MRI) and hybrid PET/MRI techniques is also analyzed, as well as the emerging applications of radiomics and artificial intelligence. The paper also discusses technical limitations, interpretative variability, and the importance of protocol standardization. The goal is to provide an updated and translational summary of imaging in LACC, with implications for clinical practice and future research. Methods: Prospective and retrospective studies, systematic reviews, and meta-analyses on adult patients with cervical cancer were included. Results: Fifty-two studies were included. MRI demonstrated a sensitivity and specificity greater than 80% for parametrial and bladder invasion, but limited sensitivity (45–60%) for lymph node disease, lower than PET/CT. Multiparametric MRI was useful in early prediction of response to chemotherapy and radiotherapy and in distinguishing residual disease from fibrosis. The integration of MRI into Image-Guided Adaptive Brachytherapy (IGABT) resulted in improved oncological outcomes and reduced toxicity. The applications of radiomics and AI demonstrated enormous potential in predicting therapeutic response and lymph node status in the MRI study, but multicenter validation is still needed. Conclusions: MRI is the cornerstone of the local–regional staging of advanced cervical cancer; it has become an essential and crucial tool in treatment planning. Its use, combined with PET/CT for lymph node assessment and metastatic disease staging, is now the standard of care. Future prospects include the use of whole-body MRI and the development of predictive models based on radiomics and artificial intelligence.

Background: Low-grade squamous intraepithelial lesions (LSIL/CIN1) are among the most common abnormalities detected in cervical cancer screening, particularly in the era of primary HPV testing. Despite their low oncogenic potential, persistence of LSIL is still frequently interpreted as a marker of progression risk, often leading to intensified surveillance or excisional treatment and raising concerns about overtreatment. Methods: We conducted a retrospective cohort study including women with persistent LSIL managed through active surveillance in a real-world clinical setting. Time-to-event analyses were performed using Kaplan–Meier estimates to evaluate CIN3-free survival. The association between HPV16 status and progression to CIN3 was assessed using Cox proportional hazards models. The proportional hazards assumption was tested using Schoenfeld residuals, and a prespecified landmark analysis at 24 months was performed to explore potential time-dependent effects. Results: A total of 82 women were included, with a median follow-up of 48 months (range 24–78). Progression to histologically confirmed CIN3 occurred in 7 cases (8.5%). Most CIN3 events (6/7, 85.7%) were diagnosed within the first 24 months of surveillance, followed by a plateau in long-term CIN3-free survival. HPV16-positive women showed a higher incidence of CIN3 compared with non-HPV16 women. In Cox regression analysis, HPV16 positivity showed a higher estimated hazard of CIN3; however, the association did not reach statistical significance and confidence intervals were wide, reflecting the limited number of outcome events. Conclusions: In women with persistent LSIL/managed by active surveillance, progression to CIN3 was uncommon and predominantly occurred early during follow-up. Long-term persistence of LSIL alone did not confer a sustained excess risk of high-grade disease. These findings support a risk-based management approach and suggest that excisional treatment based solely on LSIL persistence may contribute to overtreatment without meaningful oncologic benefit. However, given the limited number of events, the results should be interpreted cautiously and primarily as descriptive evidence.

Background: Microinvasive cervical cancer represents the earliest stage of stromal invasion and is associated with excellent oncological outcomes. Its clinical relevance arises from the potential disproportion between the limited extent of invasive disease and the morbidity of radical treatment, particularly in young women wishing to preserve fertility. Increasing evidence supports a transition from stage-based surgical radicality toward individualized, risk-adapted management. This narrative review critically examines microinvasive cervical cancer as a distinct clinical model of therapeutic de-escalation, with particular attention to the boundaries between evidence-supported conservative treatment and areas in which uncertainty persists. Methods: A narrative review of PubMed/MEDLINE was conducted for studies published between January 2010 and March 2026. Evidence concerning FIGO stages IA1 and IA2 was analyzed, focusing on diagnostic conization, pathological risk factors, lymphovascular space invasion (LVSI), margin status, histological subtype, fertility-sparing treatment, sentinel lymph node (SLN) assessment, ultrastaging, and follow-up. Studies including broader early-stage cervical cancer populations were considered only when stage IA results were separately available or clinically transferable to microinvasive disease, and were interpreted as indirect evidence when appropriate. Results: Accurate conization represents the cornerstone of the diagnosis and initial risk stratification of microinvasive cervical cancer, providing essential information on depth of stromal invasion, margin status, LVSI, histological subtype and multifocality. However, optimal risk assessment should integrate pathological findings with clinical staging, appropriate imaging and, when indicated, nodal assessment. FIGO stage alone does not adequately define individual risk, while imaging itself cannot reliably exclude occult small-volume nodal disease; therefore, the relative contribution of pathology, imaging and surgical nodal staging should be tailored to the individual risk profile. In FIGO IA1 disease without LVSI and with negative margins, conization alone provides excellent oncological control and lymph node staging is generally unnecessary. LVSI should be considered a risk modifier that may influence nodal assessment rather than an automatic indication for more radical cervical surgery. In IA1 with LVSI and IA2 disease, SLN biopsy may provide nodal staging with lower morbidity than systematic lymphadenectomy, although evidence specifically generated in microinvasive tumors remains limited. Fertility-sparing treatment is oncologically appropriate in carefully selected patients, whereas simple hysterectomy represents an adequate definitive option after completion of reproductive plans. Microinvasive adenocarcinoma requires specific consideration because of its endocervical location, potential multifocality, and the biological distinction between HPV-associated and HPV-independent histotypes. Major uncertainties remain regarding the prognostic significance of LVSI and low-volume nodal disease, the optimal indications for SLN assessment, and the limits of exclusive conservative treatment in IA2 disease. Conclusions: Microinvasive cervical cancer should not be regarded simply as the earliest anatomical stage of cervical cancer, but as a distinct clinical setting in which diagnostic precision may enable oncologically safe therapeutic de-escalation. The available evidence supports a shift from maximum surgical radicality toward the minimum effective treatment, provided that accurate histopathological assessment, appropriate patient selection, and specialized follow-up are ensured. Importantly, several recommendations for stage IA—particularly for IA2 disease and nodal management—still rely partly on evidence extrapolated from broader early-stage cervical cancer populations. Prospective multicenter studies and dedicated stage IA registries are therefore needed to define more precisely the boundaries within which therapeutic de-escalation can be safely applied.