Search Results (224)

HMGB-1 is an alarmin representative of DAMP playing a central role in immunogenic cell death (ICD), a necessary condition in the dialog established between dying tumor cells and the immune system during some anticancer therapies. Therefore, early screening for ICD inducers represents a major priority in drug development today. In this work, we investigated the effect elicited by the clinical-grade CIGB-300 peptide, which impairs Protein Kinase CK2-mediated phosphorylation and other CK2 signaling connected kinases. Here, HMGB-1 extracellular release was investigated in an 18-cell line panel from blood malignancies, uterine-cervical cancer and NSCLC treated with CIGB-300 at equipotent doses (IC₅₀) over 24 h. Interestingly, CIGB-300 treatment upregulated the HMGB-1 protein levels at the culture supernatant in most of the cell lines (p = 0.01) and fold-change increases ≥ 2 were associated with intrinsic cell line sensitivity towards CIGB-300’s cytotoxic effect. However, the HMGB-1 release by CIGB-300 was context-specific with clear induction on blood and uterine-cervical cancer cells and a diffused response pattern in NSCLC. Importantly, CIGB-300 treatment of blood cancer patients enrolled in a Phase I study induced plasma HMGB-1 alarmin in 4 out of 7 subject who received the entire treatment plan. Altogether, our data reveal for the first time that CIGB-300 treatment is able to induce extracellular HMGB-1 release in vitro and in vivo which could be indicative of ICD induction in some kinds of tumors; furthermore, the induction of extracellular HMGB-1 alarmin as a putative CIGB-300 response biomarker merits further investigation. Full article

Uterine fibroids, the most common tumors in reproductive-age women, remain without a defined precursor tissue state. Unlike cervical dysplasia preceding cervical cancer, or colonic polyps preceding colorectal malignancy, no equivalent “at-risk” tissue marker exists for fibroids, and diagnosis relies on radiological imaging only after tumors are already well-established and often symptomatic including excessive menstrual bleeding, pelvic pain, infertility and obstetric complications. In this narrative review, we propose that a subset of women with unexplained AUB may harbor a chronic, non-infectious inflammatory condition of the myometrium, which we term Chronic Aseptic Myometritis (CAM). We synthesize mechanistic and human tissue evidence suggesting that sterile inflammation driven by damage-associated molecular patterns, NLRP3 inflammasome activation, oxidative DNA damage, and TGF-β–mediated extracellular-matrix remodeling may underlie the transition from normal myometrium (MyoN) to a pre-fibroid, inflamed and stiffened state (MyoF), and may contribute both to abnormal uterine bleeding (AUB) and to fibroid initiation. We propose a preliminary framework for future CAM research, including the identification of candidate biomarker categories and imaging correlates. We also discuss whether early mechanism-based interventions, such as vitamin D and epigallocatechin gallate (EGCG), may offer a potential pathway toward primary prevention. Because the components of this model derive largely from experimental and cross-sectional human studies, CAM is presented as a hypothesis-generating, myometrium-centered framework rather than a validated clinical entity, and prospective validation is required. Full article

Background/Objectives: Angiogenesis plays a central role in the progression of cervical intraepithelial neoplasia (CIN) to cervical cancer (CC). Transvaginal Doppler ultrasonography (TVDUSG) offers a non-invasive means of assessing hemodynamic changes associated with neoplastic transformation. This study aimed to evaluate the diagnostic performance of uterine artery (UA) Doppler parameters across the full cervical disease spectrum and their associations with adverse prognostic features and clinicopathological features in CC. Methods: This prospective observational cohort study enrolled 170 patients who were divided into four groups: controls, CIN 1, CIN 2–3, and CC. All underwent TVDUSG prior to treatment. Pulsatility index (PI), resistance index (RI), peak systolic velocity (PS), end-diastolic velocity (ED), PS/ED ratio, ED/PS ratio, and time-averaged maximum velocity were recorded. ROC curve analysis was performed to assess diagnostic performance. Results: PI and RI increased progressively from controls to CC, while ED declined across groups (all p < 0.001). In patients with CC, PI correlated with tumor volume and was elevated in those with advanced-stage, parametrial and lymph node involvement (all p < 0.001). ROC analysis revealed strong diagnostic performance for PI in distinguishing CC from controls (AUC = 0.861, sensitivity 80.0%, specificity 80.4%); however, PI showed limited ability to distinguish cervical cancer specifically from high-grade CIN (AUC = 0.593). Conclusions: UA Doppler parameters, particularly PI, are associated with cervical neoplastic severity and adverse prognostic features in CC. TVDUSG may serve as a practical, non-invasive adjunct in the preoperative evaluation of cervical neoplasia, especially where advanced imaging is unavailable. Full article

The primary aim of this review is to summarize current evidence from clinical and pre-clinical studies on endogenous molecular biomarkers associated with radiosensitivity and radioresistance in cervical cancer, including patients treated with photon-based radiotherapy, cervical cancer cell lines, and xenograft models, and to evaluate the association of these biomarkers with radiotherapy response, residual disease, recurrence and survival, and experimental measures of radiosensitivity. A systematic literature review was conducted for studies published over the last 10 years that evaluated associations between genomic, epigenetic, or protein biomarkers and radiotherapy response or survival outcomes in cervical cancer. Eligible studies included in the current analysis summarize clinical, translational, and pre-clinical studies in correlation with photon-based radiotherapy. Research focusing exclusively on non-coding RNAs, exogenous radiosensitizers, or non-photon modalities was excluded. In total, 112 studies were identified, and 46 of them met the inclusion criteria. The identified biomarkers clustered into several key biological processes: DNA damage response and cell cycle regulation, cancer stemness, hypoxia and microenvironment, epigenetic and transcriptional regulation, and signaling pathways, including exosome-mediated communication. Most markers were linked to radioresistance and adverse outcomes, whereas a smaller subset was associated with increased radiosensitivity. A limited group of biomarkers was linked to clinical outcomes such as local control, residual disease, or survival, and emerging multi-marker protein signatures suggested that combinatorial approaches may outperform single-marker strategies. Radiosensitivity in cervical cancer is regulated by a network of biological pathways. Validated, integrated biomarker panels that capture DNA repair proficiency, stemness, hypoxia adaptation, and key signaling pathways are needed to improve risk stratification and enable biomarker-guided radiosensitization. Full article

Cervical cancer (CxCa) remains a major global gynecological malignancy causally linked to high-risk human papillomavirus (HPV) infection. However, HPV alone is insufficient for carcinogenesis; sex hormones and their receptors serve as essential cofactors. This review aims to synthesize current knowledge on the role of cervical histoarchitecture and hormonal microenvironments in ectocervical squamous cell carcinoma (SCC), and to explore how receptor-mediated signals contribute to malignant transformation and metastatic spread. The review examines the expression patterns of estrogen receptor α (ERα) and progesterone receptor (PR) in the uterine cervix, which is a hormone-responsive tissue. It discusses how these receptors fluctuate throughout the menstrual cycle and evaluates evidence from HPV-transgenic mouse models and human tissue analyses. The findings converge on a compelling model: stromal ERα drives pro-carcinogenic paracrine signaling, epithelial PR suppresses neoplastic transformation, and stromal PRB confers antimetastatic protection. These insights highlight the complex interplay between hormonal signals and SCC development in the ectocervix. Future therapeutic exploitation of these mechanistic insights—including selective estrogen receptor modulators, selective progesterone receptor modulators, and PR status-guided chemoprevention—holds considerable promise. This review provides a coherent framework for translating laboratory findings into clinical diagnostics and targeted interventions. Full article

At present, cervical cancer is the fourth most common cancer among women worldwide. Current treatments for cervical cancer, most notably chemotherapy, can induce various adverse side effects, such as nausea, vomiting, hair loss, and fatigue, among others. Therefore, alternative therapies are being developed. Intravaginal drug delivery systems based on biopolymers are the subject of extensive research for the treatment of this condition. Some of the most sought-after qualities in these systems are mucoadhesiveness, biocompatibility, and biodegradability, while ensuring controlled and prolonged drug release. Taking these aspects into consideration, this study develops hydrogel ovules composed of O-carboxymethyl chitosan (OCMC) and gelatin, crosslinked with genipin, containing retinyl palmitate at various concentrations, as well as curcumin. The characterization of functional groups and potential interactions between the polymeric matrix and the drugs was carried out by Fourier Transform Infrared (FTIR) spectroscopy. Physicochemical tests, including swelling, contact angle, and in vitro degradation assays, were also performed to determine the system’s hydrophilicity and its potential duration of use. In vitro release assays for both curcumin and retinyl palmitate were conducted to investigate the release kinetics of these two substances. To assess the mucoadhesiveness of the ovules, a sliding analysis was conducted using porcine uterine tissue. Finally, cell viability studies were performed using mouse fibroblasts and HeLa cells to evaluate the system’s specificity. The results of this study demonstrate that the system, composed of gelatin, OCMC, retinyl palmitate, and curcumin, is mucoadhesive, hydrophilic, and exhibits controlled swelling behavior. In vitro assays demonstrated that the system maintains control of both degradation and drug release for up to 72 h; moreover, it proved non-toxic to healthy cells, with the incorporation of curcumin shown to enhance the selective cytotoxicity against HeLa cells. Based on the foregoing, this drug delivery system containing retinyl palmitate represents a promising potential intravaginal treatment for cervical cancer. Full article

Background: Para-aortic lymph node involvement is present in approximately 17–24% of women with locally advanced cervical cancer (LACC) and is one of the strongest adverse prognostic factors in this population. Current international guidelines recommend two alternative staging techniques: the International Federation of Gynecology and Obstetrics (FIGO) and European Society of Gynecologic Oncology (ESGO) endorse imaging-based staging as the primary method to define radiation fields, whereas the National Comprehensive Cancer Network (NCCN) lists pre-treatment minimally invasive para-aortic lymphadenectomy as a Category 2B recommendation. Objective: We aimed to review and critically appraise the available evidence on the oncologic impact (progression-free and overall survival) of pre-treatment surgical para-aortic staging compared with clinical imaging-based staging in women with LACC. Methods: We searched MEDLINE (Ovid), Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), ClinicalTrials.gov, and Scopus from inception to January 2026, complemented by manually searching the reference lists for relevant articles and prior reviews. The review focused on comparative studies of women with LACC of squamous, adenocarcinoma, or adenosquamous histology—operationally defined as FIGO 2009 stages IB2–IVA with pelvic nodal involvement or FIGO 2018 stages IB3–IVA who received definitive-intent radiotherapy with or without concurrent chemotherapy and brachytherapy, and for whom comparative survival outcomes between a surgical-staging arm and an imaging-staging arm were reported. For this manuscript, a narrative review style was planned and reported in line with SANRA (Scale for the Assessment of Narrative Review Articles) quality criteria. Results: Twelve studies were included: two randomized controlled trials and ten observational studies (nine retrospective cohorts and one population-based analysis). Surgical staging consistently increased detection of occult para-aortic disease and led to more frequent use of extended-field radiotherapy (18–44%), but it did not yield a reproducible advantage in terms of progression-free or overall survival over imaging-guided chemoradiation. Conclusions: In LACC, pre-treatment surgical para-aortic staging improves anatomic and prognostic information but has not shown a consistent survival advantage over imaging-based staging combined with contemporary chemoradiation. Current comparative evidence does not support routine surgical staging, and its use still warrants further prospective evaluation in large clinical trials. Until results from ongoing phase III trials are available, surgical staging should be considered an individualized option in highly selected cases within multidisciplinary decision-making at experienced clinical centers. Full article

Background and Objectives: Uterine metastasis from breast carcinoma is rare but poses substantial diagnostic and therapeutic challenges. Invasive lobular carcinoma (ILC) demonstrates a documented predilection for unusual metastatic patterns including the female genital tract, while tamoxifen-associated endometrial pathology may complicate diagnosis in breast cancer survivors. Materials and Methods: We performed a structured PubMed/MEDLINE and Google Scholar search (1980–2025) for cases with histologically confirmed breast primary and uterine involvement; a pooled analysis of demographic, histological, molecular, and clinical variables was performed. Results: 105 individual cases were identified. ILC accounted for 58.0% of histologically classified cases despite representing only 10–15% of breast cancers. Endometrial involvement was present in 68.6%, myometrial in 25.7%, and cervical in 26.7%. Tamoxifen exposure was strongly associated with polyp-substrate metastasis (29.3% vs. 4.7%; Fisher’s exact p = 0.0009; OR 8.41, 95% CI 2.20–32.14). Abnormal uterine bleeding was the dominant presentation (68.1%); 19.8% were asymptomatic. Median latency was 36 months (range from 24 months before to 360 months after the breast cancer diagnosis). Conclusions: Uterine metastasis from breast carcinoma is dominated by invasive lobular histology and frequently involves tamoxifen-associated polyps. A combined immunohistochemical panel (GATA3, TRPS1, E-cadherin, hormone receptors, PAX8) is essential for distinguishing metastatic disease from primary uterine pathology. Endometrial sampling should be considered with a low threshold in breast cancer survivors with abnormal uterine bleeding, and breast imaging is warranted when discohesive cells are encountered without a known breast primary. These proportions describe the published case literature rather than population-based prevalence; because the evidence is limited to case reports and small series, they should not be read as the true frequency of uterine involvement among women with breast cancer. Full article

Background/Objectives: Ultrasound elastography (UE) is a non-invasive imaging technique that evaluates tissue stiffness and may complement conventional ultrasound in the assessment of uterine diseases. This systematic review aimed to summarize the current evidence on the role of strain elastography (SE) and shear wave elastography (SWE) in the diagnosis and management of benign and malignant uterine pathologies. Methods: A systematic literature search of MEDLINE (PubMed) and Embase was performed to identify studies published between January 2018 and February 2026. Original studies evaluating UE in adenomyosis, uterine fibroids, cervical lesions, and endometrial pathologies were included. Data were qualitatively synthesized according to pathology type and elastographic technique. Results: Twenty studies met the inclusion criteria. In benign myometrial disorders, adenomyosis and uterine fibroids generally showed higher stiffness than normal myometrium, although differentiation between these entities was not always consistent across studies. In cervical disease, malignant and high-grade lesions typically demonstrated increased stiffness compared with benign or low-grade lesions. In endometrial pathology, endometrial carcinoma was generally associated with higher stiffness values than benign lesions and elastography also showed potential in assessing myometrial invasion. Across studies, UE demonstrated promising diagnostic performance, but substantial heterogeneity was observed in acquisition methods, parameters, and reported thresholds. Conclusions: UE appears to be a promising adjunct to conventional ultrasound for the evaluation of uterine pathologies. However, further standardized, large-scale studies are needed to define reproducible protocols and clinically applicable diagnostic thresholds. Full article

Background: In oncologic patients, hypermetabolic neck lesions identified on F-18 fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) are often assumed to indicate nodal metastasis, especially in advanced disease. However, benign tumors such as schwannomas can also demonstrate avid F-18 FDG uptake, potentially leading to false-positive nodal staging and unwarranted assumptions of metastatic disease. Case Presentation: An 85-year-old woman with advanced uterine cervical cancer (FIGO stage IIB) underwent F-18 FDG PET/CT for staging purposes. Alongside intense uptake in the primary tumor, a hypermetabolic mass was incidentally identified in the left neck, raising concerns about nodal metastasis. Further imaging, including MRI and high-resolution ultrasonography (US), suggested a non-nodal origin, and US-guided core needle biopsy confirmed the diagnosis of a schwannoma, with histopathologic examination demonstrating characteristic Antoni A and B areas with diffuse S-100 positivity. Because the patient was elderly and repeatedly declined aggressive treatment, management was ultimately limited to symptom-directed palliative radiotherapy. Although tissue confirmation did not directly alter the delivered treatment strategy, it clarified the staging and prevented the neck lesion from being misclassified as metastatic disease. Conclusions: This case underscores that not all hypermetabolic neck lesions detected on F-18 FDG PET/CT in oncologic patients indicate metastatic lymphadenopathy. A multimodal imaging approach combined with minimally invasive tissue sampling can provide critical diagnostic clarification, particularly when PET/CT findings might otherwise lead to unsupported nodal upstaging or misguided assumptions in treatment planning. Full article

We investigated five single-nucleotide variants (SNVs) of the FN1 gene in female reproductive organ cancers. The proteins expressed by this gene are essential components of the extracellular matrix (ECM) that constitutes the tumor microenvironment (TME). The study group included 208 women diagnosed with cervical, uterine, and ovarian cancers and 208 age-matched cancer-free controls. Genomic DNA from whole blood was used to analyze five intronic SNVs of the FN1 gene using PCR/RFLP. The results indicate that two of the studied FN1 gene variants may increase the risk of gynecological cancers in dominant and log-additive models (p = 0.048 and p = 0.040 for rs6725958, p = 0.033 and p = 0.038 for rs1968510, respectively). Comparing individual cancer groups with the controls, differences were observed for the ovarian cancer group (rs1968510 p = 0.015 and p = 0.016, rs6725958 p = 0.070 and p = 0.037 in dominant and log-additive models, respectively). None of these associations remained statistically significant after Bonferroni correction for multiple testing. Haplotype analyses revealed that the AGATC haplotype, containing minor alleles for rs35343655 and rs6725958, was more frequent in the entire gynecological cancer group (p = 0.0036). For individual cancer types, values of p = 0.0071 for ovarian, p = 0.0028 for endometrial, and p = 0.0269 for cervical cancers were obtained; Our preliminary study suggests that the rs6725958 and rs1968510 FN1 variants may slightly increase the risk of female reproductive system cancers, particularly ovarian cancer. These findings require further validation in larger, independent cohorts and functional studies. Full article

Background/Objective: RNA modifications, including N⁶-methyladenosine (m⁶A), 5-methylcytosine (m⁵C), 7-methylguanosine (m⁷G), N¹-methyladenosine (m¹A), pseudouridine (Ψ), N⁴-acetylcytidine (ac⁴C), 5-methoxycarbonylmethyl-2-thiouridine (mcm⁵s²U) and adenosine-to-inosine (A-to-I) editing, constitute a critical layer of post-transcriptional regulation that influences RNA stability, splicing, translation and degradation. This review aims to systematically summarise the current understanding of the molecular mechanisms and regulatory networks of RNA modifications in the female reproductive physiology and to evaluate their pathological implications in obstetric and gynaecologic disorders. Methods: We conducted a comprehensive literature review, synthesising findings from high-throughput sequencing studies, functional experiments and clinical investigations. The review integrates evidence across multiple RNA modification types, their regulatory enzymes (writers, erasers and readers) and their roles in physiological processes (germ cell development, oocyte maturation, embryogenesis and endometrial function) and pathological conditions (gynaecologic cancers, preeclampsia, endometriosis, polycystic ovary syndrome and premature ovarian insufficiency). Results: RNA modifications function as dynamic and reversible regulators that orchestrate key reproductive events, including primordial germ cell differentiation, oocyte meiosis, the maternal-to-zygotic transition, the establishment of uterine receptivity, and placental development. These modifications operate through coordinated writer–eraser–reader networks that fine tune transcripts’ stability, translation efficiency and RNA decay. The dysregulation of these epitranscriptomic networks is strongly implicated in the pathogenesis of gynaecologic malignancies (cervical, ovarian, endometrial cancers and choriocarcinoma), pregnancy-related disorders (preeclampsia, gestational diabetes mellitus and recurrent miscarriage), reproductive endocrine disorders (polycystic ovary syndrome and premature ovarian insufficiency) and benign gynaecological conditions (endometriosis and adenomyosis). Emerging evidence also reveals complex crosstalk among RNA modifications, such as cooperative interactions between m⁶A and m⁵C in translation regulation and antagonistic relationships between m⁶A and A-to-I editing. Conclusions: RNA modifications represent an essential and multifaceted regulatory layer in female reproduction, with broad implications for disease pathogenesis. Their unique reversibility and context-dependent functions offer promising opportunities for the development of diagnostic biomarkers and targeted therapeutic interventions. Future researchers should prioritise integrated multi-omics approaches, enhanced human-relevant models and clinical translation to fully realise the potential of epitranscriptomic medicine in reproductive health. Full article

Background: Sub-Saharan Africa is undergoing a rapid epidemiological transition marked by a growing burden of non-communicable diseases, including breast, cervical, ovarian, and uterine cancers, which constitute major causes of morbidity and mortality among women in the region; however, comprehensive assessments of long-term trends and regional heterogeneity remain limited. This study examines the burden and temporal trends of breast, cervical, ovarian, and uterine cancers across sub-Saharan Africa from 1990 to 2023. Methods: A retrospective ecological analysis was conducted using data from the latest Global Burden of Disease 2023 study. Age-standardised incidence rates, mortality rates, and disability-adjusted life year rates were estimated for breast, cervical, ovarian, and uterine cancers across 48 sub-Saharan African countries and four sub-regions. Temporal trends were assessed from 1990 to 2023, with percentage changes calculated to characterise epidemiological transitions. Geographic variation and age-specific patterns were examined to identify high-burden settings and priority populations. Results: Between 1990 and 2023, the burden of all four cancers increased substantially across sub-Saharan Africa, with significant regional and country-level heterogeneity. Breast cancer exhibited the largest absolute burden, with incidence increasing by over 120 percent and mortality by more than 80 percent, particularly in Central and Western Africa. Cervical cancer remained the leading cause of cancer-related mortality among women in Eastern and Southern Africa, despite evidence of stabilisation or decline in selected countries. Ovarian and uterine cancers demonstrated sustained upward trends, especially in Central Africa, with high mortality-to-incidence ratios indicating late diagnosis and limited treatment access. Across all cancer types, Central and Eastern sub-Saharan Africa consistently experienced the highest disability-adjusted life year burdens. Conclusions: The burden of the selected cancers in sub-Saharan Africa has increased markedly over the past three decades, with persistent regional inequities reflecting gaps in prevention, early detection, and treatment capacity. Strengthening cancer surveillance systems, expanding equitable access to screening and vaccination programmes, and improving diagnostic and treatment infrastructure are critical to reversing current trends. These findings provide region-specific evidence to guide cancer control priorities and resource allocation across sub-Saharan Africa. Full article

Background/Objectives: To examine long-term incidence trends of cervical cancer and corpus uteri cancer in Taiwan from 1995 to 2022, with emphasis on age–period–cohort patterns and regional variation. Methods: Data from the Taiwan cancer registry were analyzed. Age-standardized incidence rates (ASRs) were calculated using the 1976 World Standard Population. Temporal trends were evaluated using Joinpoint regression to estimate annual percent changes (APCs) and average annual percent changes (AAPCs). Age–period–cohort modeling was applied to assess net drift, cohort effects, and period effects. Subgroup analyses were conducted by geographic region and urbanization level. Results: Cervical cancer incidence declined markedly, with ASRs decreasing from 20.06 to 6.78 per 100,000 women between 1995 and 2022 (AAPC = −4.43%, 95% CI: −5.39 to −3.45). In contrast, corpus uteri cancer incidence increased substantially, with ASRs rising from 2.91 to 17.42 per 100,000 women (AAPC = 6.32%, 95% CI: 5.86–6.78). Age–period–cohort analysis revealed a negative net drift for cervical cancer (−5.0% per year) and a positive net drift for corpus uteri cancer (6.1% per year). Cohort effects indicated decreasing cervical cancer risk among women born after 1960, whereas corpus uteri cancer risk increased in successive younger cohorts. Period effects showed pronounced declines in cervical cancer incidence after 2000, patterns that are compatible with the implementation of organized screening, while corpus uteri cancer continued to rise. Conclusions: Cervical cancer incidence in Taiwan has declined substantially over the past three decades, a pattern that is compatible with the long-term impact of organized screening programs. In contrast, the increasing burden of corpus uteri cancer may be associated with generational shifts in metabolic and reproductive risk factors. Full article

Background: CDKN2A (p16^INK4a^) is integral to the regulation of the RB–E2F cell-cycle checkpoint and is widely acknowledged as a surrogate marker for high-risk human papillomavirus (HPV)-related cervical neoplasia. Nevertheless, its diagnostic and prognostic significance in uterine corpus endometrial carcinoma (UCEC), a predominantly HPV-independent malignancy, remains inadequately characterized. This study utilized an integrated multi-omics approach to examine CDKN2A dysregulation in cervical squamous cell carcinoma (CESC) and UCEC. Methods: Pan-cancer and tumor–normal differential expression analyses were performed using TIMER2.0 and GEPIA2 (TCGA/GTEx). Clinicopathological correlations were assessed with UALCAN. Protein expression patterns were analyzed using immunohistochemistry data from the Human Protein Atlas (HPA). Prognostic significance and immune-infiltration associations were evaluated using TCGA survival data and TIMER modules. Independent transcriptomic validation and diagnostic classification performance were assessed using GEO datasets GSE9750 (CESC) and GSE63678 (UCEC), including ROC-AUC analysis with cross-validation. Results: Integrated analyses revealed elevated CDKN2A expression in both CESC and UCEC across multiple transcriptomic cohorts, with pronounced tumor-specific protein expression on immunohistochemistry. TCGA-only tumor–normal RNA comparisons were non-significant, likely due to limited normal sample representation. In independent GEO cohorts, CDKN2A exhibited excellent tumor–normal discrimination in CESC (AUC = 0.982) and moderate discrimination in UCEC (AUC = 0.761). Survival analysis indicated tumor-specific patterns, with limited prognostic stratification in CESC and context-dependent associations in UCEC. Immune-infiltration analysis suggested tumor-type-specific interactions between CDKN2A expression and immune cell subsets. Conclusions: CDKN2A exhibits strong diagnostic performance in HPV-associated cervical cancer and moderate, cohort-dependent discriminatory ability in endometrial carcinoma. These findings reinforce its established diagnostic role in CESC and propose adjunctive utility in UCEC, underscoring the importance of tumor-contextual interpretation of CDKN2A expression in gynecologic malignancies. Full article