Background/Objectives: Human papillomavirus (HPV) is the most common sexually transmitted virus worldwide and is frequently detected in women of reproductive age. In this population, HPV-related diseases and their management may affect reproductive health and pregnancy outcomes. This narrative review summarizes the current evidence on HPV infection and HPV-related diseases in relation to fertility, pregnancy, and neonatal outcomes, and discusses preventive strategies, with a particular focus on HPV vaccination. Methods: An international, multidisciplinary team of clinicians from the European Society of Gynaecological Oncology (ESGO) Prevention Committee reviewed the literature on HPV, HPV-related diseases, HPV vaccination, and reproductive outcomes, without time restrictions, prioritizing studies judged to meaningfully reflect the available evidence. Results: The most consistent evidence linking HPV-related conditions to adverse pregnancy outcomes relates to the treatment of cervical precancer, particularly excisional procedures, which are associated with an increased risk of preterm birth and mid-trimester pregnancy loss. In contrast, evidence that maternal HPV detection alone causes adverse pregnancy or neonatal outcomes remains limited and inconsistent. Data on HPV infection and subfertility are scarce and heterogeneous. Management of HPV-related lesions during pregnancy remains challenging and requires careful balancing of maternal safety with avoidance of unnecessary interventions. HPV DNA has been detected in neonatal samples, but convincing evidence for clinically relevant vertical transmission is lacking. Available data indicate that inadvertent HPV vaccination shortly before or during pregnancy is not associated with adverse pregnancy outcomes. Conclusions: Current evidence suggests that reproductive risks are more strongly associated with the treatment of HPV-related diseases than with HPV infection itself. Preventive strategies—especially HPV vaccination—remain central to reducing HPV-related disease burden. Although HPV vaccines are not routinely recommended during pregnancy, evidence supports the safety of inadvertent exposure around conception or during gestation, while potential long-term benefits of vaccination regarding reproductive health require further study.
BACKGROUND:To compare outcomes between older (≥ 70 years) and younger (< 70 years) patients with surgically treated endometrial cancer, evaluating the Prognostic Nutritional Index (PNI), Systemic Immune-Inflammation Index (SII), and Age-Adjusted Charlson Comorbidity Index (ACCI). METHODS:This retrospective cohort study included 319 patients who underwent surgery at a tertiary center (2014-2024). Demographics, pathology, treatment, and outcomes were analyzed. Perioperative morbidity was graded (Clavien-Dindo). Frailty (ACCI), PNI, and SII were assessed. Overall survival and disease-specific survival were analyzed in parallel; Kaplan-Meier analyses were performed overall and stratified by stage and histology. Major morbidity was analyzed with multivariable logistic regression. RESULTS:Of 319 patients, 93 (29.2%) were aged ≥ 70 years. Older patients more frequently exhibited high-grade histology, advanced stage, ASA III-IV status, high ACCI, and low PNI. Admissions to the intensive care unit were higher in older patients, but major morbidity (4.3% vs. 3.5%; p = 0.60) and 30-day mortality (1.1% vs. 0.9%; p = 0.60) were comparable between groups. Low PNI demonstrated moderate discriminatory ability for major complications. In multivariable analysis, low PNI (odds ratio 5.78; p = 0.012) and ASA III-IV (odds ratio 3.89; p = 0.047) were independently associated with major morbidity, whereas age ≥ 70 was not. For overall survival, higher PNI remained protective (hazard ratio 0.48 per 5-point increase; p < 0.001) and ASA III-IV predicted worse outcomes (hazard ratio 3.80; p = 0.002); however, chronological age was not an independent predictor. CONCLUSION:Older age is associated with more aggressive tumor biology but not with higher rates of major complications. PNI and ASA class are independent predictors of major morbidity and survival and should be integrated into perioperative risk stratification rather than using chronological age alone.
BACKGROUND:Concerns that human papillomavirus (HPV) vaccination may adversely affect ovarian reserve contribute to vaccine hesitancy, yet longitudinal data with paired anti-Müllerian hormone (AMH) measurements are limited. We evaluated whether HPV vaccination was associated with short-term changes in AMH compared with an unvaccinated control group. METHODS:In this retrospective cohort, women aged 18-45 years who completed a three-dose 9-valent HPV vaccination (Gardasil 9®, Merck Sharp & Dohme LLC, West Point/Pennsylvania/USA) schedule and had AMH measured before dose 1 and after dose 3 were compared with unvaccinated controls who had two AMH measurements during routine gynecologic evaluation. AMH change was summarized as absolute change (ΔAMH), percent change, and log change. To compare rates of AMH change while accounting for heterogeneous follow-up and confounding, AMH was analyzed on the natural log scale using a linear mixed-effects model with a random intercept for participant and fixed effects for time (years), group, and a time × group interaction, adjusted for age, current smoking, gravidity, and parity. Annual percent change was derived from model coefficients. Prespecified sensitivity analyses repeated the primary model under follow-up restrictions and after restricting baseline AMH to 1.0-5.0 ng/mL. RESULTS:The cohort included 158 vaccinated and 106 control women. Baseline AMH was similar between groups (median 1.88 vs. 1.94 ng/mL), while the follow-up interval was shorter in vaccinated women (6.7 vs. 8.9 months). Unadjusted AMH decline was smaller in vaccinated women (median ΔAMH -0.13 vs. -0.27 ng/mL; p = 0.015; median percent change -10.9% vs. -20.6%; p = 0.006). In the adjusted mixed-effects model, controls showed an estimated AMH decline of -27.6% per year (95% CI -35.5% to -18.7%; p < 0.001). The time × group interaction was positive (β = 0.170, 95% CI 0.027 to 0.312; p = 0.020), corresponding to a slope ratio of 1.185 (95% CI 1.02-1.366) and an implied annual change of -14.2% per year (95% CI -21.0% to -6.7%) in vaccinated women. Results were broadly consistent in follow-up-restricted sensitivity analyses; however, in the baseline AMH 1.0-5.0 ng/mL restricted cohort (vaccinated n = 82, control n = 67), the interaction was attenuated and not statistically significant (β = 0.082, p = 0.237). CONCLUSIONS:In this retrospective cohort with paired AMH measurements, HPV vaccination was not associated with evidence of clinically meaningful short-term impairment in ovarian reserve as assessed by AMH. Observed differences in AMH alterations were modest and should be interpreted cautiously, given residual confounding, measurement variability, and reduced precision in restricted-cohort analyses.
Background/Objectives: The levonorgestrel-releasing intrauterine device (LNG-IUD) is widely used as a long-acting reversible contraceptive and as a therapeutic option for heavy menstrual bleeding, endometriosis, adenomyosis, and endometrial hyperplasia. Although its predominant effect is local, systemic levonorgestrel exposure has raised questions regarding its potential influence on cancer risk. This review aims to summarise and critically appraise the available evidence on the association between LNG-IUD use and gynaecologic, breast, and selected non-gynaecologic malignancies (including colorectal, lung, pancreatic, gastric, thyroid, skin [melanoma], and haematological cancers). Methods: A structured narrative review was developed by a multidisciplinary expert group affiliated with the European Society of Gynaecological Oncology (ESGO) and the European Society for Gynaecological Endoscopy (ESGE). PubMed/MEDLINE, Embase, and Scopus were searched in December 2024 without publication-date restrictions. We critically appraised epidemiological and clinical evidence on LNG-IUD use and breast, endometrial, ovarian, cervical, and selected non-gynaecologic cancer risks, prioritising population-based cohorts, registry-based studies, case-control studies, systematic reviews, and meta-analyses. Results: The strongest and most consistent evidence supports a substantial reduction in endometrial cancer risk among LNG-IUD users, with a possible protective association also suggested for ovarian cancer. Available data do not indicate a clear increase in cervical cancer, CIN3+, or invasive cervical disease. In contrast, evidence for breast cancer remains heterogeneous, with some registry-based studies suggesting a modest relative increase and other cohort or case-control studies showing no significant association. Evidence regarding non-gynaecologic cancers remains limited and inconclusive. Conclusions: Overall, current evidence suggests that the LNG-IUD has a favourable oncological safety profile, with the strongest evidence supporting a significant reduction in endometrial cancer risk and a potential protective effect against ovarian cancer. There is no evidence pointing to increased risk of cervical cancer. However, results related to breast cancer are mixed, and a slight risk increase cannot be ruled out; thus, counselling should be personalised based on the indication, menopausal status, duration of use, and individual breast cancer risk.
Background: Persistent cervical human papillomavirus (Human papillomavirus) infection remains a significant public health concern, as it is the primary etiological factor in the development of cervical cancer and its precursor lesions. While prophylactic vaccination and standard screening programs are cornerstones of prevention, a substantial proportion of women with established infection are managed conservatively, often with prolonged follow-up and associated psychological burden. Interest has therefore grown in supportive interventions that may facilitate viral clearance during routine clinical management. Methods: This retrospective cohort study included 239 women with confirmed cervical Human papillomavirus infection followed at a tertiary referral center between February 2023 and August 2025. Participants were classified into a treatment group receiving oral Papivir/Pavirona® twice daily for six months (n = 119) and a control group managed with routine clinical follow-up alone (n = 120). Human papillomavirus DNA testing and cervical cytology were evaluated at baseline and at 6 and 12 months. Results: Human papillomavirus clearance rates were significantly higher in the Papivir/Pavirona® group compared with controls at both 6 and 12 months. Cytological regression was also more frequent in the treatment group at both time points. In multivariate logistic regression analysis, Papivir/Pavirona® use emerged as the only independent predictor of both Human papillomavirus clearance and cytological regression, while demographic, reproductive, behavioral, and virological baseline characteristics were not significantly associated with outcomes. Conclusions: Papivir/Pavirona® supplementation was associated with increased Human papillomavirus clearance and cytological regression rates in women with cervical Human papillomavirus infection, suggesting a potential supportive role alongside standard clinical follow-up.
Next-generation human papillomavirus (HPV) vaccines encompass newly licensed and emerging formulations that employ alternative production platforms, expanded valency, or novel antigenic targets beyond conventional L1-based vaccines. These vaccines aim to address affordability challenges, supply limitations, and suboptimal vaccination coverage, particularly in low- and middle-income countries. This review aggregates current clinical, immunological, and programme-related evidence on newly licensed vaccines, including the World Health Organization (WHO)-prequalified bivalent formulations (Cecolin® and Walrinvax®), the quadrivalent Cervavac®, and the Escherichia coli-derived nonavalent Cecolin 9®, which received national licensure in 2025. Additionally, emerging high-valency candidates in Phase I–III trials—9-valent, 11-valent, and 14-valent formulations—are critically assessed. Clinical trials demonstrate that next-generation HPV vaccines provide robust protection; for example, Cecolin® showed 100% efficacy against HPV-16/18-associated high-grade squamous intraepithelial lesions (HSIL) and up to 97.8% efficacy against persistent HPV infection, while Walrinvax® demonstrated 78.6% protection against CIN2+ lesions. Cervavac® showed non-inferior immunogenicity compared with established vaccines. While comparative analyses of efficacy, immunogenicity, and safety indicate that these vaccines are strong alternatives to established products, robust long-term effectiveness and real-world impact data remain essential before full clinical equivalence can be definitively established. Advances in L2-based platforms further aim to broaden cross-type protection, simplify manufacturing, and enable thermostable formulations, thereby enhancing applicability in resource-limited settings. Economic evaluations demonstrating favorable cost-effectiveness emphasize the essential role of next-generation vaccines in improving access and reducing inequity. Overall, innovations in valency, technology, and delivery strategies have the potential to significantly expand global HPV prevention coverage and accelerate progress toward cervical cancer elimination.
Intravascular leiomyomatosis (IVL) and benign metastasizing leiomyoma (BML) are uncommon variants of uterine smooth muscle tumors that can demonstrate extrauterine spread despite their benign histological appearance. Both lesions are known to be estrogen-dependent, yet their coexistence with gynecologic malignancies-particularly endometrial carcinoma-is exceedingly rare. We present a 51-year-old postmenopausal woman who was admitted with progressive abdominal distension and ecchymotic skin changes over the abdominal wall. Radiologic evaluation revealed a large retroperitoneal mass with multiple solid pelvic lesions. The patient underwent total abdominal hysterectomy, bilateral salpingo-oophorectomy, omentectomy, and resection of a para-aortic mass. Histopathological examination identified 3 concurrent entities: intravascular leiomyomatosis confined to the uterus, benign metastasizing leiomyoma involving para-aortic lymph nodes, and an incidental FIGO stage IA1 endometrioid adenocarcinoma confined to an endometrial polyp. Immunohistochemistry confirmed smooth muscle differentiation (Desmin, h-caldesmon), retained FH expression, low proliferative index (Ki-67 ≈ 2%-3%), and wild-type p53 pattern. Postoperative recovery was uneventful, and adjuvant hormonal suppression with letrozole was initiated. The patient remains disease-free during 6 months of follow-up. This case represents an exceptionally rare triple coexistence of IVL, BML, and early-stage endometrial carcinoma. Recognition of such unique associations broadens the understanding of estrogen-dependent uterine neoplasms and emphasizes the need for thorough histopathological and immunohistochemical evaluation. A multidisciplinary approach with long-term hormonal surveillance is recommended to detect recurrence or additional hormone-responsive lesions.
Background/Objectives: Non-ablative local therapies are increasingly used in the conservative management of human papillomavirus (HPV) infection. Coriolus versicolor, an immunomodulatory medicinal mushroom, is one such approach. This study aimed to investigate the effect of a Coriolus versicolor-based vaginal gel on HPV clearance and cervical cytological outcomes. Methods: This retrospective cohort study included 600 women with cervical HPV infection (300 treated with a Coriolus versicolor-based vaginal gel and 300 receiving standard follow-up). Baseline and six-month follow-up assessments included HPV DNA testing and cervical cytology. Results: Baseline demographic characteristics, HPV genotype distribution, infection type, and cytological findings were comparable between the groups. Overall HPV clearance was significantly higher in the treatment group than in the controls (89.3% vs. 44.7%, p < 0.001). Complete clearance of high-risk HPV genotypes, including HPV 16 (77.0% vs. 25.4%, p < 0.001) and HPV 18 (73.9% vs. 18.5%, p = 0.017), was also significantly more frequent among treated women. Cytological normalization occurred more often in the treatment group (88.4% vs. 60.4%, p < 0.001). Multivariable analysis identified use of the vaginal gel as the strongest independent factor associated with HPV clearance (adjusted odds ratio [aOR] = 10.19; 95% confidence interval [CI]: 3.52-29.47; p < 0.001). Conclusions: Treatment with a Coriolus versicolor-based vaginal gel was associated with significantly higher rates of high-risk HPV clearance and cervical cytological normalization. These findings suggest that this therapy may represent an effective adjunct in the conservative management of HPV infection; however, randomized controlled trials are warranted to confirm these results.
Severe obesity raises endometrial cancer (EC) risk and worsens outcomes. Combining metabolic bariatric surgery (MBS) with minimally invasive hysterectomy in a single encounter may streamline care. Following PRISMA 2020, we searched Scopus, Web of Science, and PubMed (final search January 2026) with a deliberately broad search strategy to identify all reports of concomitant MBS and gynecologic oncologic surgery in adult women with severe obesity and either EC or endometrial intraepithelial neoplasia (EIN). Five studies (n = 19) met eligibility. All procedures were minimally invasive. Operative time was longer than for hysterectomy alone, without increased major morbidity or hospital stay. Six-month excess weight loss ranged 42–72
Background/Objectives: Uterine adenosarcoma is a rare uterine malignancy with limited evidence on prognostic factors and long-term outcomes. We aimed to evaluate clinicopathological characteristics, treatment patterns, oncologic outcomes, and prognostic factors associated with disease-free survival (DFS) and overall survival (OS) in patients with uterine adenosarcoma. Methods: This multicenter retrospective cohort study included 43 patients with histopathologically confirmed uterine adenosarcoma who underwent primary surgery at seven tertiary referral centers in Türkiye between 2016 and 2026. Clinicopathological features, treatment modalities, recurrence patterns, and survival outcomes were assessed. Survival was analyzed using Kaplan–Meier and log-rank methods, and multivariable Cox proportional hazards regression was performed to identify independent prognostic factors. Results: The mean age at diagnosis was 59.1 ± 10.8 years, and 83.7% of patients were postmenopausal. Pelvic pain (62.8%) and abnormal uterine bleeding (60.5%) were the most common presenting symptoms. Most patients (79.1%) underwent laparotomy, and 79.1% had stage I disease. Sarcomatous overgrowth (SO) was present in 44.1% and lymphovascular space invasion (LVSI) in 18.6%. During a median follow-up of 72 months, 34.9% experienced recurrence, most commonly in the pelvis. The five-year DFS and OS rates were 59.9% and 80.4%, respectively. SO was independently associated with DFS (HR 4.41, 95% CI 1.21–16.08; p = 0.025) and OS (HR 10.23, 95% CI 1.16–89.80; p = 0.036), while LVSI was independently associated with OS (HR 11.17, 95% CI 1.34–93.14; p = 0.026). Conclusions: Uterine adenosarcoma showed favorable long-term survival but substantial recurrence risk. SO and LVSI may have potential prognostic relevance and could contribute to postoperative risk assessment and individualized follow-up.
Background/objectives: The study aimed to present cases of malignant struma ovarii from seven centers in Türkiye and evaluate them within the context of the existing literature. Methods: We retrospectively analyzed clinical data from 17 patients treated at seven centers, focusing on clinical features, surgical management, pathology, thyroid function, adjuvant treatment, and outcomes. Additionally, a literature review including eight studies with 178 patients was conducted. Results: The mean age of patients was 44.7 years, with a mean tumor size of 9.2 cm. Elevated Ca 125 was found in 33.3% of patients, while thyroid function abnormalities and hyperthyroidism signs were rare. Pelvic pain and menstrual irregularities were common presenting symptoms. A total of 16 patients (94.1%) had unilateral tumors. Total abdominal hysterectomy with bilateral salpingo-oophorectomy and unilateral salpingo-oophorectomy were the most frequent surgical approaches. Histopathology predominantly showed classical papillary thyroid carcinoma (13 patients, 76%). All patients were FIGO stage I, with no metastasis. Thyroidectomy was performed in seven patients, identifying two concurrent thyroid cancers. Four patients received adjuvant radioactive iodine therapy. During a median follow-up of 43 months, no deaths and one recurrence were observed. The literature review showed a diagnosis age ranging 43–53 years and papillary thyroid carcinoma as the most common subtype. Thyroidectomy and RAI treatment were selectively applied. Among the reported studies, recurrence occurred in 7 of 76 patients (9.2%), while 5-year disease-free and overall survival rates exceeded 94% and 100%, respectively. BRAF mutations were uncommon. Conclusions: Malignant struma ovarii is a rare tumor with a favorable prognosis when diagnosed early and managed appropriately.
Objective: To demonstrate the robotic-assisted Davydov technique for neovaginal creation in Mayer-Rokitansky-Kuster-Hauser syndrome. Design: Stepwise demonstration of the technique with narrated video. Subjects: A 27-year-old patient has been diagnosed with Mayer-Rokitansky-Kuster-Hauser syndrome since the age of 18 years. Three months ago, vaginal dilation was attempted at another medical center but was unsuccessful because of intolerance. Pelvic examination revealed a shallow vaginal dimple. Exposure: After identification of the anatomical structures, the rectovaginal and vesicovaginal spaces were dissected, creating a space for the neovaginal canal and forming anterior and posterior peritoneal flaps. After complete dissection of the rectum from the posterior pelvic peritoneum, the vaginal remnant was bluntly dissected externally under guidance of a blunt-tipped curette handle and connected adequately to the introitus. Subsequently, the created anterior and posterior flaps were individually interrupted with sutures to form the neovaginal entrance. After the neovaginal entrance was established, the robot was used again to continuously suture the uterine remnants to create the anterior neovaginal wall. The uterine remnants, rectal serosa, and internal portions of the flaps were then joined together to form the neovaginal vault. Main Outcome Measures: Demonstration of the steps for the robotic management of neovaginal creation in Mayer-RokitanskyKuster-Hauser syndrome. Results: The patient was discharged on postoperative day 1 with a soft mold in the vagina. On postoperative day 3, the soft mold was replaced with a medium-sized rigid mold. By postoperative day 6, the patient could insert a full-size rigid mold. The patient achieved full penetration and engaged in sexual activity within 1 month, with no postoperative complications observed. At the 8-month follow-up, the neovaginal cavity measured 13.4 cm in depth and 4.7 cm in diameter. Conclusion: Creating a neovagina using the robotic-assisted Davydov technique in patients with Mayer-Rokitansky-Kuster-Hauser syndrome is a safe, feasible, beneficial, and highly effective method. Although the superiority of robotic systems over laparoscopy has not yet been fully established through extensive publications, the advantages provided by high-image quality, magnification, and maneuverability are highlighted in this study. Robotic technology could be particularly beneficial for patients with obesity or those with complex pelvic anatomy because of prior surgeries.
Objective:This study aimed to assess the likelihood of detecting cancer in final pathology and evaluate the accuracy of intraoperative frozen-section assessment in cases of endometrioid intraepithelial neoplasia (EIN). Material and methods:We included patients diagnosed with EIN at Hacettepe University Hospital who subsequently underwent hysterectomy at the same center between January 2011 and March 2023. EIN diagnoses made at other institutions were re-evaluated and confirmed by co-author gynecopathologists. Results:A total of 354 patients diagnosed with EIN underwent hysterectomy. The majority of patients (68.5%) had a final diagnosis of EIN. Endometrial cancer (EC) was identified in 11.3% (n = 40) of patients in the final pathology. Advanced age (≥50 years) (OR = 2.52; 95% CI: [1.27-4.96]; p = 0.006) and menopausal status (OR = 2.62; 95% CI: [1.34-5.11]; p = 0.004) were significantly associated with an increased risk of EC. Among 263 patients who underwent intraoperative frozen-section assessment, EC was detected in 12.9% (n = 34). The sensitivity and specificity of frozen-section assessment for EC detection were 41.1% and 100%, respectively. The frozen-section assessment failed to identify only one of the seven patients who required staging surgery. Conclusion:Our study demonstrates that a preoperative EIN diagnosis carries an 11.3% risk of concurrent EC. Additionally, the likelihood of EC is significantly higher in older and postmenopausal patients. The majority of patients requiring staging surgery were identified by frozen-section assessment. Our findings indicate that frozen-section assessment provides the necessary information for adequate surgical treatment in EIN cases.