OBJECTIVE: This study aimed to investigate the incidence, risk factors and trends for vaginal cancer.
METHODS: Retrospective observational design.
METHODS: Data were collected from multiple sources, including the Global Cancer Observatory, Cancer Incidence in Five Continents Plus, Global Burden of Disease, World Bank and the United Nations.
METHODS: Individuals diagnosed with vaginal cancer.
METHODS: The study collected data on vaginal cancer from the specified sources. The age-standardised rate (ASR) of vaginal cancer was calculated for different regions and age groups. Multivariable and univariable linear regression analyses were performed to examine the associations between risk factors and the incidence of vaginal cancer. Trend analysis was conducted using joinpoint regression analysis, and the average annual percentage change (AAPC) was calculated to quantify the temporal trend.
METHODS: The main outcome measures of the study were the incidence of vaginal cancer, risk factors associated with the disease and the trend of its incidence over time.
RESULTS: There were 17 908 newly reported cases of vaginal cancer (ASR = 0.36, 95% CI 0.30-0.44) in 2020, with the highest ASRs reported in South-Central Asia and Southern Africa. Risk factors associated with a higher incidence of vaginal cancer included a higher prevalence of unsafe sex and human immunodeficiency virus (HIV) infection. The temporal trend showed an overall rising incidence globally, with Iceland (AAPC = 29.56, 95% CI 12.12-49.71), Chile (AAPC = 22.83, 95% CI 13.20-33.27), Bahrain (AAPC = 22.05, 95% CI 10.83-34.40) and the UK (AAPC = 1.40, 95% CI 0.41-2.39) demonstrating the most significant rising trends.
CONCLUSIONS: The significant regional disparities and risk factors associated with vaginal cancer underscore the necessity for targeted interventions and education, particularly in regions with a lower human development index (HDI) and a higher prevalence of human papillomavirus (HPV) infection. The increasing incidence trend emphasises the need for enhanced HPV vaccination rates to prevent the development of vaginal cancer.

OBJECTIVE: Around 70% of vaginal cancers and 40-50% of vulvar cancers are attributable to human papillomavirus (HPV). Globally the burden of these diseases is estimated to grow due to the increasing HPV prevalence and rapidly aging global population. We aimed to examine if HPV screening for cervical cancer has an additional beneficial effect in preventing vaginal and vulvar cancers. To assess this, we used long-term follow-up data from the Finnish randomized HPV screening trial.
METHODS: Between 2003 and 2008, over 236,000 women were individually randomized (1:1) to primary HPV or cytology screening in Southern Finland. We followed this cohort up to the year 2020. To compare the study arms, we calculated site-specific and pooled incidence rate ratios (IRRs) and mortality rate ratios (MRRs) for vaginal and vulvar cancers using Poisson regression.
RESULTS: During 3,5 million person-years of follow-up, the IRR for vaginal cancer in the HPV arm compared to the cytology arm was 0.40 (95% CI 0.17-0.88) and the corresponding MRR was 0.74 (95% 0.21-2.24). The corresponding IRR for vulvar cancer was 0.73 (95% 0.50-1.08) and the MRR was 0.64 (95% 0.23-1.62). The pooled IRR was 0.67 (95% 0.47 ̶ 0.95) and MRR 0.67 (95% 0.31 ̶ 1.37).
CONCLUSIONS: We found lower incidence of vaginal cancers with HPV screening compared to cytology screening. To validate our results, we recommend analyzing data on vaginal and vulvar cancers also from other HPV screening studies.

OBJECTIVE: Vaginal intraepithelial neoplasia (VaIN) is a rare human papillomavirus (HPV)- related premalignant condition. VaIN lesions are diagnosed histologically through colposcopy-guided biopsies of suspicious areas, conduced by gynecologists with expertise in lower genital tract diseases. The present study aimed to evaluate the accuracy of colposcopy in the diagnosis of VaIN of any grade.
METHODS: We conducted a retrospective analysis on a cohort of 149 women diagnosed with low grade (LG)-VaIN (VaIN1) and high grade (HG)-VaIN (VaIN2-3) between 2010 and 2022 at the \"Regional Referral Center for Prevention, Diagnosis and Treatment of HPV-related Genital Disorders\", Ospedale Maggiore Policlinico, Milan, Italy. All women had been referred to our center for an abnormal Pap smear or as part of routine follow-up of other HPV-related diseases and had undergone a vaginal biopsy under colposcopic guidance.
RESULTS: The distribution of the histological grades of VaIN lesions was the following: 62 women (41.6%) were diagnosed with VaIN1, 51 (34.2%) with VaIN2, and 36 (24.2%) with VaIN3. Grade II (major) abnormal colposcopic patterns were recorded in 71 cases (47.7%) and were more commonly observed in women with VaIN3 (80.6%). However, we found a poor and not statistically significant association between colposcopic and histological grade of VaIN. The sensitivity, specificity, positive predictive value, and negative predictive value of colposcopy for histologically confirmed VaIN were 56.3%, 64.5%, 69% and 51.2%, respectively. The overall diagnostic accuracy of colposcopy was 59.7%.
CONCLUSIONS: Colposcopy-guided biopsy plays an important role in the diagnosis of VaIN and in the distinction between low and high-grade lesions. Our data show that major colposcopic abnormalities moderately correlate with HG-VaIN and that grade I colposcopic findings do not exclude HG-VaIN, especially VaIN2. Targeted biopsies of suspicious vaginal areas must be performed in all women with an abnormal Pap smear.

(1) Background: Vaginal intraepithelial neoplasia (VaIN) is a rare premalignant disease caused by persistent human papillomavirus (HPV) infection. Diagnosing VaIN is challenging; abnormal cytology and positive HPV tests are usually the first signs, but published data on their accuracy for detecting it are rare and contradictory. The aim of this study is to compare the results of hrHPV and cytology co-testing with the histological findings of the vagina. (2) Methods: In the certified Dysplasia Unit at Erlangen University Hospital, cytology and HPV samples from the uterine cervix or vaginal wall after hysterectomy were obtained between 2015 and 2023 and correlated with histological findings in biopsies from the vaginal wall. Women without vaginal biopsy findings or concomitant cervical disease were excluded. (3) Results: In all, 279 colposcopies in 209 women were included. The histological results were: benign (n = 86), VaIN I/vLSIL (n = 116), VaIN II/vHSIL (n = 41), VaIN III/vHSIL (n = 33), and carcinoma (n = 3). Accuracy for detecting VaIN was higher in women with previous hysterectomies. Positive HPV testing during colposcopy increased the likelihood for VaIN II/III/vHSIL threefold. The detection rate for VaIN III/vHSIL was 50% after hysterectomy and 36.4% without hysterectomy. (4) Conclusions: Women with risk factors for VaIN, including HPV-16 infection or prior HPV-related disease, need careful work-up of the entire vaginal wall. Hysterectomy for HPV-related disease and a history of cervical intraepithelial neoplasia (CIN) also increased the risk for VaIN II/III/vHSIL.

OBJECTIVE: We aimed to evaluate the risk of reoperation and uterine (myometrial, endometrial, and cervical) and vaginal cancer after colpocleisis performed during the years 1977-2018. Furthermore, we also aimed to assess the development in colpocleisis procedures performed during the study period.
METHODS: Danish nationwide registers covering operations, diagnoses, and life events can be linked on an individual level owing to the unique personal numbers of all Danish residents. We performed a nationwide historical cohort study including women born before year 2000 who underwent colpocleisis between 1977 and 2018 (N = 2,228) using the Danish National Patient Registry (DNPR). We followed the cohort until death/emigration/31 December 2018, whichever came first. Primary outcomes were number of pelvic organ prolapse (POP) operations performed after colpocleisis and uterine and vaginal cancer diagnosed after colpocleisis in a subgroup of women with the uterus in situ. This was assessed with cumulative incidences.
RESULTS: During follow-up (median 5.6 years) 6.5% and 8.2% underwent POP surgery within 2 and 10 years after colpocleisis respectively. Within 10 years after colpocleisis 0.5% (N = 8) were diagnosed with uterine or vaginal cancer in the subgroup of women with their uterus (N = 1,970). During the study time 37-80 women underwent colpocleisis yearly and the mean age increased (77.1 to 81.4 years).
CONCLUSIONS: Despite smaller studies showing no recurrence after colpocleisis, we found that 6.5% underwent reoperation within 2 years. Few women were diagnosed with uterine or vaginal cancer after colpocleisis. The increased age at the time of colpocleisis indicates changed attitudes regarding surgical treatment for elderly women with comorbidities.

OBJECTIVE: To analyze the prognosis and treatment decisions for patients with vaginal cancer through a large retrospective cohort study, in order to assist clinicians to evaluate the condition and choose treatment methods.
METHODS: This was a retrospective study analyzed with Cox regression, nomogram, and external validation. The Kaplan-Meier curve was used for comparative analysis of various treatment modalities.
RESULTS: A total of 6650 cases of vaginal cancer diagnosed between 2000 and 2018 from the Surveillance, Epidemiology, and End Results database and 106 cases diagnosed between 2006 and 2021 from Fujian Cancer Hospital were identified. Young age, early FIGO (the International Federation of Gynecology and Obstetrics) stage, well-differentiated, squamous and adenocarcinoma, first primary malignancy, married, undergoing surgery, and chemoradiotherapy were good independent prognostic factors (P < 0.001). The internal and external validation concordance indices were 0.7102 and 0.7785, respectively. The Kaplan-Meier curves indicated that surgery, radiotherapy, and chemotherapy significantly improved survival in patients with vaginal cancer. Forest plots suggest that radiotherapy combined with surgery was superior to radiotherapy alone (P < 0.001).
CONCLUSIONS: We established a specific nomogram to predict vaginal cancer prognosis. Surgery combined with external beam radiation plus brachytherapy may be the most recommended treatment option.

OBJECTIVE: The aim of this study was to analyze trends in the incidence of vaginal cancer in France over a 28-year period and to present survival for recently-diagnosed women.
METHODS: French cancer registries provided data on invasive vaginal cancers diagnosed from 1990 to 2015 and followed up through June 2018. Trends in incidence were analyzed using a Poisson model with a bidimensional penalized spline of age and year at diagnosis. Net survival analysis was restricted to recently-diagnosed cases (2010-2015) and used a novel approach based on a bidimensional penalized spline of age and time-since-diagnosis to model excess mortality hazard.
RESULTS: With 162 new cases estimated in France in 2018, vaginal cancer represented 0.9 % of genital cancers in French women. In 2018, the world population age-standardized incidence rate was 0.2 per 100,000 person-years, median age at diagnosis was 75 years. The standardized incidence rate decreased significantly by 3 % per year (95 % CI, -3.8; -2.2) between 1990 and 2018 (0.4 cases per 100,000 person-year in 1990, vs 0.2 in 2018). Age-standardized net survival at 1 and 5 years after diagnosis was respectively 74 % and 45 %.
CONCLUSIONS: This study confirms that vaginal cancer is still a rare malignancy in France with 5-year net survival that remains low. We observed a consistent decrease in the incidence rate between 1990 and 2018. It may be too early to attribute these trends to a positive impact of vaccination campaigns against hrHPV infection, since vaginal cancer mainly affects older women and HPV vaccination has only been available since the early 2000s, and only targets young girls.

UNASSIGNED: No models have been developed to predict the survival probability for women with primary vaginal cancer (VC) due to VC\'s extreme rareness. We aimed to develop and validate models to predict the overall survival (OS) and cancer-specific survival (CSS) of VC patients.
UNASSIGNED: A population-based multicenter retrospective cohort study was carried out using the 2004-2018 Surveillance, Epidemiology, and End Results Program database in the United States. The final multivariate Cox model was identified using the Brier score and Harrell\'s C concordance statistic (C-statistic). The decision curve, calibration plot, and area under the time-dependent receiver operating characteristic curve (AUC) were used to evaluate model prediction performance. Multiple imputation followed by bootstrap was performed. Bootstrap validation covered the entire statistic procedure from model selection to baseline survival and coefficient calculation. Nomograms predicting OS and CSS were generated.
UNASSIGNED: Of the 2,417 eligible patients, 1,692 and 725 were randomly allocated to the training and validation cohorts. The median age (Interquartile range) was 66 (56-78) and 65 (55-76) for the two cohorts, respectively. Our models had larger net benefits in predicting the survival of VC patients than the American Joint Committee on Cancer stage, presenting great discrimination ability and excellent agreement between the expected and observed events. The performance metrics of our models were calculated in three cohorts: the training cohort, complete cases of the validation cohort, and the imputed validation cohort. For the OS model in the three cohorts, the C-statistics were 0.761, 0.752, and 0.743. The slopes of the calibration plots were 1.017, 1.005, and 0.959. The 3- and 5-year AUCs were 0.795 and 0.810, 0.768 and 0.771, and 0.770 and 0.767, respectively. For the CSS model in the three cohorts, the C-statistics were 0.775, 0.758, and 0.755. The slopes were 1.021, 0.939, and 0.977. And the 3- and 5-year AUCs were 0.797 and 0.793, 0.786 and 0.788, and 0.757 and 0.757, respectively.
UNASSIGNED: We were the first to develop and validate exemplary survival prediction models for VC patients and generate corresponding nomograms that allow for individualized survival prediction and could assist clinicians in performing risk-adapted follow-up and treatment.

Although appetite and its disorders have been implicated in disease progression and outcomes, ghrelin concentrations, an objective appetite measure, are rarely assessed in patients with gynecological malignancies. The present study aimed to assess changes in post-operative versus pre-operative appetite levels in patients with gynecological cancers scheduled for tumor removal surgery (N = 53). Acylated ghrelin concentrations were assessed as an objective appetite proxy, whereas the Council of Nutrition appetite questionnaire (CNAQ) was employed as a subjective appetite measure. Ghrelin concentrations were increased post-operatively (median: 12.1 pg/mL, IQR: 0.67 to 23.5, p-value = 0.001) but the perceived appetite of patients (CNAQ) remained unchanged (median: -1, IQR: -3 to 1). Tumor removal surgery decreased all anthropometric indices (body weight, body mass index, waist and hips circumferences, triceps skinfolds, body fat, fat mass and fat mass index, p-value ≤ 0.001 for all) and doubled the risk of malnutrition among patients. No difference was recorded in the change in participants\' objective and subjective appetite when they were classified according to the tumor type. No correlation was observed between ghrelin concentrations and CNAQ score pre-operatively (Spearman\'s rho correlation coefficient = -0.181, p-value = 0.298) or post-operatively (Spearman\'s rho correlation coefficient = 0.071, p-value = 0.684). The observed post-operative rise in ghrelin concentrations is associated with body weight loss and consists of a possible defense mechanism of the human body, aiming to prolong survival.

Recently, the Varian multichannel vaginal cylinder (MCVC) set for high-dose-rate 192Ir brachytherapy was commercially released. This MCVC was distinct from our existing MCVC in its peripheral channel layout and tip design. This investigation sought to assess the dosimetric impact of these changes.
The dimensions of the virtual model for each applicator were compared against both physical and radiographic measurements. Volumetric dose distributions were generated in silico using a model-based dose calculation algorithm (MBDCA). To characterize the effects of the new peripheral channel layout on dose to adjacent areas (\"dose-spill\"), point doses were compared using two sets of applicator-based reference points: at surface or 5 mm radially from surface. To evaluate the dose-shaping capabilities, a dose distribution was generated for the new applicator and assessed against a representative dose distribution for a patient previously treated with existing equipment.
Based on both physical and radiographic measurements, virtual models were representative of each applicator within ±1 mm. Commissioning of the MBDCA was benchmarked based on AAPM Working Group on Dose Calculation Algorithms in Brachytherapy. The layout of the new applicator reduced dose-spill to other reference points significantly, as much as a factor of 16.3, compared with the existing equipment. The rounded tip shape and curve of the peripheral channels in the new applicator produced more conformity to its HR-CTV than existing equipment.
Compared with our existing equipment, the design changes in the new Varian MCVC set offered improved control of dose spill and better conformality to HR-CTV.