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Background and Aim: The present meta-analysis aims to investigate a potential link between pelvic inflammatory disease (PID) and an increased risk of genitourinary cancers (ovarian, cervical, uterus, and vagina cancers). While previous research has hinted at a possible link, this meta-analysis seeks to delve deeper into the available evidence. Understanding this association is crucial for preventive strategies and improving clinical management practices., Methodology: A comprehensive literature search was conducted across various databases, covering studies published between 2016 and 2024. We included 13 observational studies meeting stringent criteria, followed by meticulous data extraction and quality assessment. Meta-analytical techniques were then employed to calculate pooled odds ratios (ORs), adjusted hazard ratios (HRs), and 95% confidence intervals (CIs), with heterogeneity assessed using the I 2 statistic., Results: Our analysis revealed significant findings, underscoring the association between PID and increased risks of genitourinary cancers. Specifically, individuals with a history of PID demonstrated notably higher odds of developing ovarian cancer (OR = 1.477, 95% CI 1.033-2.207), uterine cancer (OR = 1.263, 95% CI 0.827-2.143), cervical cancer (OR = 1.000, 95% CI 0.900-1.100), and vaginal cancer (OR = 2.500, 95% CI 1.400-4.000) compared to those without such a history. The overall heterogeneity across studies was high (I 2  = 82.92%), suggesting varying trends across different populations and study designs., Conclusion: This meta-analysis provides updated evidence supporting a significant association between PID and an increased risk of cervical, ovarian, and uterine cancers. Early detection and management of PID are crucial in potentially mitigating the risk of these cancers., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: Human papillomavirus (HPV) is the most common sexually transmitted infection, responsible for multiple HPV-related diseases, including almost all cervical cancers. The highly effective HPV vaccination has been recommended under the German HPV national immunization program (NIP) since 2007 and is reimbursed by health insurances. Vaccination uptake rates, however, remain suboptimal and data on the real-world impact of HPV vaccination in Germany are lacking. This study aims to demonstrate the population-level impact of Germany's NIP on HPV-related anogenital diseases among young women., Methods: Retrospective claims data analysis using a classic impact study design comparing disease prevalence among 28- to 33-year-old women before and after introduction of the HPV-immunization program in Germany. Claims data representing approximately two thirds of German health insurances were used. HPV-related disease outcomes included cervical cancer and high grade precancers (cervical intraepithelial neoplasia (CIN) 2+), anogenital warts, as well as vulvar, vaginal, and anal precancer/cancer., Results: Significant declines were seen for CIN2+, anogenital warts, and vaginal precancer/cancer. Prevalence of CIN2+ declined 51.1% from 0.92% (95% CI = 0.78%, 1.08%) to 0.45% (95% CI = 0.38%, 0.53%). There was a 38.6% decline in anogenital warts prevalence from 0.44% (95% CI = 0.36%, 0.54%) to 0.27% (95% CI = 0.22%, 0.32%) and 75.0% decline in vaginal precancer/cancer prevalence from 0.04% (95% CI = 0.02%, 0.07%) to 0.01% (95% CI = 0.00%, 0.02%)., Conclusion: The German HPV-immunization program has led to significant declines in female anogenital disease among young women in Germany, highlighting the importance of the vaccination. Moreover, the data suggest that increasing vaccination coverage in Germany could further strengthen the public-health impact of its HPV-immunization program., (© 2024. Merck & Co., Inc., Rahway, NJ, USA and its affiliates & Monika Hampl 2024.)

Objective: This study aimed to investigate the incidence, risk factors and trends for vaginal cancer., Design: Retrospective observational design., Setting: 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., Population: 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., Main Outcome Measures: 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., (© 2024 The Author(s). BJOG: An International Journal of Obstetrics and Gynaecology published by John Wiley & Sons Ltd.)

Objective: To investigate the high-risk factors associated with concurrent cervical intra-epithelial neoplasia (CIN) and vaginal intra-epithelial neoplasia (VaIN) in patients with high-grade lesions., Methods: This retrospective study at the Obstetrics and Gynecology Hospital of Fudan University included patients diagnosed with concurrent CIN2/3 and VaIN2/3 (concurrent group) over the period from January 1, 2019, to December 31, 2019. Patients with only CIN2/3 during the corresponding period were selected chronologically on a 1:2 basis (CIN group). Demographic data, human papillomavirus (HPV) infection rates, genotypes, and cytology results were compared between the groups., Results: A total of 128 patients were included. The median age in the concurrent group was 50 years (range 20-79), which was significantly higher than the median age of 38 (range 23-72) in the CIN group (p<0.001). The cytological sensitivity for identifying high-grade lesions was markedly higher in the concurrent group at 83.1% (103 out of 124) compared with 68.4% (175 out of 256) in the CIN-only group (p=0.002). The prevalence of HPV 16 was 62.8% in the concurrent group, significantly higher than 51.6% in the CIN group (p=0.04)., Conclusions: The risk of concurrent VaIN2/3 increases with age among women with CIN2/3. Cytology screening is effective for detecting concurrent VaIN2/3, with a sensitivity of 83.1%., Competing Interests: Competing interests: None declared., (© IGCS and ESGO 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

To summarize the distribution of types of human papillomavirus (HPV) associated with HPV-related diseases and investigate the potential causes of high prevalence of HPV 52 and 58 by summarizing the prevalence of lineages, sub-lineages, and mutations among Chinese women. We searched PubMed, EMBASE, CNKI, and WanFang from January, 2012 to June, 2023 to identify all the eligible studies. We excluded patients who had received HPV vaccinations. Data were summarized in tables and cloud/rain maps. A total of 102 studies reporting HPV distribution and 15 studies reporting HPV52/HPV58 variants were extracted. Among Chinese women, the top five prevalent HPV types associated with cervical cancer (CC) were HPV16, 18, 58, 52, and 33. In patients with vaginal cancers and precancerous lesions, the most common HPV types were 16 and 52 followed by 58. For women with condyloma acuminatum (CA), the most common HPV types were 11 and 6. In Chinese women with HPV infection, lineage B was the most prominently identified for HPV52, and lineage A was the most common for HPV58. In addition to HPV types 16, which is prevalent worldwide, our findings revealed the unique high prevalence of HPV 52/58 among Chinese women with HPV-related diseases. HPV 52 variants were predominantly biased toward lineage B and sub-lineage B2, and HPV 58 variants were strongly biased toward lineage A and sub-lineage A1. Further investigations on the association between the high prevalent lineage and sub-lineage in HPV 52/58 and the risk of cancer risk are needed. Our findings underscore the importance of vaccination with the nine-valent HPV vaccine in China.

We aimed to investigate human papillomavirus (HPV) prevalence and genotype distribution and prognostic factors in vaginal cancer (VC). VC patients who received treatment between 1989 and 2020 were retrospectively reviewed. L1 general polymerase chain reaction (PCR) followed by HPV Blot (King Car, I-Lan, Taiwan) and E6 type-specific-PCR were performed for genotyping firstly. P16 and p53 immunohistochemistry staining was performed. Univariate and multivariate analyses identified predictors of clinical outcomes.79 VC patients were eligible for analysis. 73 patients (92.4%) were squamous cell carcinoma (SCC) and 6 (7.6%) as non-SCC. The median follow-up time was 134.3 months (range 0.9-273.4). Among nine initially HPV-negative cases, seven were identified as being positive through HPV16/18/45/52/58 whole-genome amplification followed by Sanger sequencing (WGASS). HPV DNA sequences were detected in 98.6% of SCC and 83.3% of non-SCC, respectively, with HPV16 (49.4%), HPV52 (15.2%) and HPV58 (8.9%) being predominant. Patients with paraaortic lymph node (LN) metastasis had a 5-year cancer-specific survival (CSS) rate of 0%. Multivariate analysis revealed that only p16 and stage were significantly correlated with prognosis. Variables with strong correlations (p16- and HPV-positivity, LN metastasis and stage), were included in models 2-5 alternatively. Stage III/IV (hazard ratio [HR] = 3.64-4.56) and LN metastasis (HR = 2.81-3.44) were significant negative predictors of CSS, whereas p16-positivity (HR = 0.29-0.32) and HPV-positivity (HR = 0.14) were related to better prognosis. In conclusion, 97.5% of VCs were HPV-positive with WGASS. Stage III/IV and LN metastasis were significant negative predictors, whereas p16- and HPV-positivity were significantly associated with better prognosis., (© 2024 The Author(s). International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

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)., Conclusion: 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., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:, (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Human papillomavirus (HPV) proteins may elicit antibody responses in the process toward HPV-related malignancy. However, HPV seroepidemiology in noncervical HPV-related cancers remains poorly understood, particularly in populations with a high prevalence of human immunodeficiency virus (HIV). Using a glutathione S-transferase-based multiplex serology assay, antibodies against E6, E7 and L1 proteins of HPV16 and HPV18 were measured in sera of 535 cases of noncervical HPV-related cancers (anal (n = 104), vulval (n = 211), vaginal (n = 49), penile (n = 37) and oropharyngeal (n = 134)) and 6651 non-infection-related cancer controls, from the Johannesburg Cancer Study that recruited Black South African with newly diagnosed cancer between 1995 and 2016. Logistic and Poisson regression models were used to calculate adjusted odds ratios (aOR) and prevalence ratios (aPR) and 95% confidence intervals (CI) in cases versus controls. HPV16 E6 was more strongly associated with noncervical HPV-related cancers than HPV16 L1 or E7, or HPV18 proteins: anal (females (HPV16 E6 aOR = 11.50;95%CI:6.0-22.2), males (aOR = 10.12;95%CI:4.9-20.8), vulval (aOR = 11.69;95%CI:7.9-17.2), vaginal (aOR = 10.26;95%CI:5.0-21), penile (aOR = 18.95;95%CI:8.9-40), and oropharyngeal (females (aOR = 8.95;95%CI:2.9-27.5), males (aOR = 3.49;95%CI:1.8-7.0)) cancers. HPV16-E6 seropositivity ranged from 24.0% to 35.1% in anal, vulval, vaginal and penile cancer but was significantly lower (11.2%) in oropharyngeal cancer. After adjustment for HIV, prevalence of which increased from 22.2% in 1995-2005 to 54.1% in 2010-2016, HPV16 E6 seropositivity increased by period of diagnosis (aPR for 2010-2016 vs. 1995-2006 = 1.84;95%CI:1.1-3.0). Assuming HPV16 E6 seroprevalence reflects HPV attributable fraction, the proportion of certain noncervical-HPV-related cancers caused by HPV is increasing over time in South Africa. This is expected to be driven by the increasing influence of HIV., (© 2024 International Agency for Research on Cancer. International Agency for Research on Cancer retains copyright and all other rights in the manuscript of this article as submitted for publication.)

High-risk human papillomavirus (hrHPV) is the cause of virtually all cervical cancers, most vaginal and anal cancers, and some vulvar cancer cases. With HPV testing becoming the primary screening method for cervical cancer, understanding the link between cervical hrHPV infection and the risk of other anogenital cancers is crucial. We assessed the risk of vulvar, vaginal and anal cancer and precancer (VIN2+, VaIN2+ and AIN2+) in a prospective cohort study including 455,349 women who underwent cervical hrHPV testing in Denmark from 2005 to 2020. We employed Cox proportional hazard models, adjusting for age, calendar year and HPV vaccination status, and estimated hazard ratios (HRs) and 95% confidence intervals (CI). We used the Aalen Johansen estimator to calculate the absolute risks of VIN2+, VaIN2+ and AIN2+. In total, 15% of the women were hrHPV positive at baseline. A positive cervical hrHPV test was associated with increased incidence of vulvar, vaginal and anal squamous cell carcinoma (SCC). Five-year risk estimates of VIN2+, VaIN2+ and AIN2+ among hrHPV-positive women (0.45%, 0.14% and 0.12%) were higher than among hrHPV-negative women (0.14%, 0.01% and 0.05%). Particularly high risk was observed among the hrHPV-positive women of the oldest age, with a history of anogenital precancer and those not HPV vaccinated. In conclusion, our study confirms the association between cervical hrHPV infection and non-cervical anogenital precancers and cancers. Currently, no established risk threshold or guidelines for follow-up. As HPV testing becomes the primary method for cervical cancer screening, future data will help define high-risk groups and acceptable risk thresholds., (© 2024 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

Purpose: This study aimed to explore the clinical characteristics and risk factors associated with cervical intraepithelial neoplasia (CIN) when coexisting with vaginal intraepithelial neoplasia (VAIN)., Methods: We analyzed the clinical data of 212 patients diagnosed with CIN, including 50 patients with concurrent VAIN. The groups were compared to identify distinct clinical features and independent risk factors for the co-occurrence of CIN and VAIN, using logistic regression analysis., Results: Patients with both CIN and VAIN had a median age of 57, significantly older than the 41-year median age of patients with CIN only (P < 0.05). A higher prevalence of HPV infection (98.0%) was observed in the CIN and VAIN group, with a notable rate of multiple HPV infections (67.3%) compared to the CIN-only group (P < 0.05). Educational levels were significantly lower in the combined CIN and VAIN group (P < 0.05). HPV16, 33, and 52 were identified as significant types for single and multiple infections. Multivariate analysis confirmed age as an independent risk factor for CIN with VAIN (P < 0.05). VAIN3 patients were more likely to exhibit HSIL and ASC-H, whereas VAIN1 cases tended to correspond with ASCUS and LSIL diagnoses., Conclusion: The co-occurrence of CIN and VAIN is significantly influenced by patient age and educational level. The findings advocate for more diligent vaginal examination during colposcopy in older patients, particularly those with multiple HPV infections and cytological abnormalities, to enhance the early detection of vaginal lesions and prevent missed diagnoses and treatments. Additionally, the high prevalence of HPV infection, especially with certain types, underscores the importance of HPV monitoring in this patient population., (© 2024. The Author(s).)

Background: To date, few studies on the factors related to vaginal intraepithelial neoplasia (VaIN) have been published. In this study, we aimed to analyze the features of VaIN and identify underlying risk factors., Methods: Patients with VaIN or vaginitis histologically confirmed at the Industrial Street Branch of Chengdu Women's and Children's Central Hospital from July 2020 to December 2021 were included. We statistically analyzed their baseline clinical characteristics, human papillomavirus (HPV) infection status, cytology results, and pathology results. Categorical indicators were analyzed using the chi-square test or Fisher's exact test, as appropriate. Differences were considered to be statistically different with p < 0.05., Results: A total of 62 patients with VaIN (mean age: 39.06 ± 11.66 years) and 32 with vaginitis (mean age: 41.13 ± 13.43 years) were included. Synchronous cervical intraepithelial neoplasia (CIN) was histologically identified in 46 (74.2%) patients with VaIN and 7 (21.9%) with vaginitis (p < 0.001). Low-grade squamous intraepithelial lesions (LSILs) and atypical squamous cells of undetermined significance (ASC-US) were the most frequent cytological abnormalities in both groups. Patients with VaIN only (62.5%) were more likely to be negative for intraepithelial lesion or malignancy than patients with synchronous CIN (32.6%; p = 0.036). No statistically significant difference in HPV infection was noted between patients with VaIN and those with vaginitis (p = 0.439). The most prevalent HPV genotype in patients with VaIN or vaginitis was HPV16, whereas both HPV58 and HPV16 were the most common in patients with concurrent CIN., Conclusions: Attention should be paid to HPV16- and HPV58-positive patients with cytological abnormalities such as ASC-US and LSILs (especially with synchronous CIN) to avoid misdiagnosis or underdiagnosis and to facilitate early interventions for VaIN., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Objectives: We aimed to evaluate the risk of cervical and vaginal clear cell adenocarcinoma (CCA) in women, aged 50 years or more, exposed in utero to diethylstilbestrol (DES) and contribute to a reevaluation of the recommendations for cervical and vaginal cancer and pre-cancer screening for these women., Methods: We carried out a retrospective review for patients received in a cancer institute. Two cohorts were consecutively studied, the first from 1970 to 2003 and the second from 2004 to 2021, and then linked., Results: During the first period, we observed 61 CCA cases, with a mean age at diagnosis of 23 years (7-42), 36 (59%) following DES exposure in utero. During the second period, we found 27 cases, with one case of DES exposure (4%) for a women diagnosed at the age of 40 years. The mean age of the second cohort was 38 years (14-79). For the seven women aged 50 years or more at the time of CCA diagnosis, DES exposure was excluded for five and considered unlikely for the other two., Conclusion: In total, 88 cases of cervical or vaginal CCA were observed over a period of 51 years in a cancer center. The 37 cases associated with DES exposure represented approximatively one third of the CCA related to DES expected in France. DES exposure was improbable for the seven cases of CCA for women aged 50 years or more. These results do not support the hypothesis of late cervical or vaginal CCA in women exposed to DES in utero and indicate the need for larger multicentric studies. For the present, we propose specific screening for women exposed to DES in utero in terms of : 1) methods: association of cytology and hrHPV testing, with cervical and vaginal sampling, 2) timing : annual, or without exceeding a three-year interval, continuing after 65 years of age and after hysterectomy., Competing Interests: Declaration of Competing Interest The authors report no competing interests., (Copyright © 2023. Published by Elsevier Masson SAS.)

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., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objectives: Women exposed to diethylstilbestrol (DES) in utero have an increased risk of clear cell adenocarcinoma of the lower genital tract, requiring lifelong cervical and vaginal cancer screening. We examined the incidence of DES-related cancers in postmenopausal women 50 years and older., Materials and Methods: We conducted a retrospective chart review of patients 50 years and older exposed to DES in utero who received care at our institution. Patients were identified using billing codes and/or searching through the electronic record for the word DES. With this 2-pronged approach, we reviewed a total of 503 charts with confirmed DES exposure to identify gynecologic cancer occurrence., Results: Within the 503 selected charts, 28 cases of gynecologic cancer occurrence were identified. Ten patients had cervical cancer and one patient had vaginal cancer. Only 1 woman of 503 developed a DES-related cervical or vaginal malignancy after age 50 years. No patients were diagnosed with cervical or vaginal cancer after age 65 years., Conclusions: Diethylstilbestrol-related malignancies are rare in those older than 50 years. Current cervical cancer screening guidelines recommend cessation of screening in an average risk, adequately screened patient at age 65 years, but patients exposed to DES have historically received lifelong screening. However, we found no cases of cervical or vaginal cancer related to DES after age 65 years, suggesting that screening recommendations could be changed for these patients to align with current screening guidelines., Competing Interests: The authors have declared they have no conflicts of interest., (Copyright © 2022, ASCCP.)

Objectives: The race, age, and region-stratified incidence of vulvar (VUC) and vaginal (VAC) cancers with different histology were unclear. Methods: Data was retrieved from the United States Cancer Statistics database. Average annual percent change (AAPC) and incidence rate ratio (IRR) were calculated. Results: Overall, VUC incidence increased from 18.3 (per 1,000,000 woman-years) to 19.6, but VAC incidence decreased from 5.6 to 4.4. VUC squamous cell carcinoma (SCC) incidence increased (AAPC, 0.96; 95% CI, 0.66-1.25), VUC adenocarcinoma (ADE) incidence stabilized (AAPC, -0.24; 95% CI, -1.44 to 0.98), and VUC other malignancies (OM) incidence decreased (AAPC, -1.31; 95% CI, -2.58 to -0.02). While VAC incidence decreased for any histology (AAPC, -0.63; 95% CI, -1.03 to -0.22; AAPC, -1.60; 95% CI, -2.80 to -0.39; and AAPC, -1.57; 95% CI, -2.24 to -0.89 for SCC, ADE, and OM). Similar trends were observed in most of the stratifications. Conclusion: VUC and VAC incidences varied by histology overall and within stratifications by race, age, and region. The incidence decreased for VUC and VAC with all histologies, except for the increasing VUC SCC incidence., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhou and Yue.)

Purpose: Women exposed to diethylstilbestrol (DES) in utero were at elevated risk of clear-cell adenocarcinoma of the vagina and cervix (CCA) as young women. Previous research suggested that this elevated risk of CCA may persist into adulthood. We extended a published analysis to measure CCA risk as these women aged., Methods: Standardized incidence ratios (SIR) compared CCA risk among women born from 1947 through 1971 (the DES-era) to CCA risk among the comparison group of women born prior to 1947, using registry data that covered the US population., Results: Incidence rates of CCA among both cohorts increased with age. Among the DES-era birth cohort, higher rates of CCA were observed across all age groups except 55-59 years. SIR estimates had wide confidence intervals that often included the null value., Conclusions: Results are consistent with prior research and suggest an elevated risk of CCA in midlife and at older ages among women exposed in utero to DES. These results highlight unresolved issues regarding cancer risk among aging DES daughters and appropriate screening guidance. The examination of population-based cancer surveillance data may be a useful tool for monitoring trends in the incidence of other rare cancers over time among specific birth cohorts., (© 2022. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Objective: To investigate the clinical, pathological, and genetic characteristics of patients with vaginal melanoma in a nationwide setting., Materials/methods: All patients diagnosed with vaginal melanoma from 1980 to 2018 were collected by searching the digital archives of the Danish Registry of Pathology (Patobank). Patient specimens were examined, the histological diagnoses were validated, and targeted next-generation sequencing (NGS) of known frequent hot spots in 163 genes was performed., Results: Fifty-two patients were included. The incidence for primary melanoma of the vagina in the Danish population (5.5 million people) was calculated to be 0.24 cases/million/year from 1980 to 2018. For all patients, the median OS was 17.5 months (95% CI: 13.0-24.0), and the 5-year OS was 19.4% (95% CI: 10.9-34.3). We identified frequent mutations in ATRX (7/25 cases) and TP53 (7/25 cases). Mutations found in TP53 were associated with a significant decrease in OS (p = 0.043), whereas mutations in the ATRX gene alone did not show a significant impact on OS (p = 0.3649). Patients who harbored co-mutations in both ATRX and TP53 showed a significant reduction in OS (p = 0.0081), with a median OS of 9.5 months compared to 20 months in those without the co-mutation., Conclusions: Vaginal melanoma is a rare disease with a poor prognosis presumably due to vague symptoms and the anatomical location of the disease. Co-mutations in ATRX and TP53 and mutations in TP53 alone were associated with a poor prognosis, and these genes are potentially interesting targets for future therapy., Competing Interests: Declaration of Competing Interest None of the authors had a personal or financial conflict of interest., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: A simple hysterectomy is considered the definitive treatment modality for cervical intraepithelial neoplasia (CIN). However, it is associated with recurrence of vaginal intraepithelial neoplasia (VAIN) of up to 7.4%. We sought to determine recurrence rates of VAIN, in women living with HIV (WLWH) and non-infected women., Methods: This was a descriptive retrospective review of patients who received a simple hysterectomy for CIN between January 2015 and December 2017 in Pietermaritzburg., Results: Fifty-eight files were reviewed. Forty-two (72.4%) WLWH were seen; amongst those, 76.2% were virally suppressed. Abnormal vault cytology was only seen in patients with CIN grades 2 and 3. The recurrence rates for high-grade squamous intraepithelial lesion (HSIL) were 6.1% and 5.0% at 6 and 12 months, respectively. Human immunodeficiency virus co-infection was associated with 26.2% versus 13.3% of abnormal vault cytology compared to the HIV-negative counterparts (p = 0.164). Virologically suppressed patients had more abnormal cytology (28.1% vs. 0%) compared to the unsuppressed patients. There was a 17.2% and 65.5% loss- to follow-up rates at 6 and 12 months, respectively. Recurrence of premalignant lesions was noted amongst those who had the abdominal approach., Conclusion: The recurrence rates were comparable to the previous literature. A 6-month cytology follow-up showed no added benefit. Human immunodeficiency virus co-infection didn't show a statistical significance on the recurrence rates; however, more structured studies are required to address this. Primary health care-based post operative surveillance can be a solution to address high loss to follow-up.

Objectives: In total, 80,000 women were exposed to diethylstilbestrol (DES) in utero in France (DES daughters) between 1950 and 1977. After having been dominated by the management of infertility and pregnancy accidents, monitoring must adapt to the increased risk of cancer of the cervix and vagina: doubling of the frequency of severe dysplasia and a risk of late clear-cell adenocarcinoma (CCA). Two recent changes in cervical cancer screening in France, the introduction of HPV tests in first-line screening and organized screening, should consider the particular situation of DES daughters. We aimed to assess the compliance of DES daughters with previous recommendations and propose specific screening practices in the new context., Method: A non-profit organization carried out a questionnaire survey of its members who were exposed to DES in utero., Results: Among the 570 participants, 64 % had annual PAP tests, 25 % within the last three years, and 11 % more than three years before or never. The reasons for "dropout" were: 1) ignorance of the recommendations by practitioners (38 %) or patients (30 %), 2) fatigue (32 %) or apprehension of the exams (14 %), and 3) difficult access to care: time to get an appointment (26 %), difficulty in finding a doctor (28 %), or cost (6 %)., Conclusion: These results concern women who were sufficiently aware of the issue to be a member of an association. They are encouraging but show a need to improve the dissemination of information to all "DES daughters" and health professionals. Patient associations can play a growing role in this "rare disease" by addressing patients and healthcare professionals. We propose that screening for these women include an annual screen of not only the cervix, but also the vagina, and that it continues beyond 65 years of age and after hysterectomy, with cytological examination, because ACC is unrelated to HPV., Competing Interests: Declaration of Competing Interest The authors report no declarations of interest., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Objectives: To investigate the incidence of vaginal intraepithelial neoplasia (VaIN) after total hysterectomy and, subsequently, optimize the follow-up strategy of patients after hysterectomy., Methods: This retrospective study was conducted on 8581 patients with benign gynecology disease who underwent total hysterectomy in our institution between January 2006 to December 2017, including 834 patients with cervical intraepithelial neoplasia (CIN) and 7747 patients without cervical lesions before hysterectomy. All patients underwent postoperative high-risk human papilloma virus (Hr-HPV) screening and liquid-based cytology test (LCT) as confirmatory tests. Colposcopies were performed if the results of the confirmatory tests were abnormal, and biopsies were performed depending on colposcopy images. The mean follow-up time was 33.8 ± 12.1 months. The relationship among VaIN, CIN, and confirmatory test results was investigated., Results: VaIN was found in 81 patients after hysterectomy (incidence rate, 0.9%). The incidence rates of VaIN in patients with and without CIN history were significantly different (7.3%, 61/834, vs 0.3%, 20/7747; P < 0.05). Compared with patients without CIN history, those with CIN history were more likely to have abnormal LCT results in the postoperative follow-up, especially low-grade squamous intraepithelial lesions or worse (P < 0.001). Patients with high-grade squamous intraepithelial lesions in the LCT have a high VaIN incidence (patients with CIN history, 57.1%; patients without CIN history, 15.1%), and the 2 patients with squamous cell carcinoma or adenocarcinoma (SCC/AC) in the LCT had CIN and VaIN or worse after hysterectomy. The Hr-HPV infection rates after the hysterectomy of patients with and without CIN history were 18.8% (157/834) and 5.4% (419/7747), respectively. The incidences morbidities of VaIN in patients with persistent Hr-HPV infection and in those with and without CIN history were 35.7% and 12.0%, respectively, and were significantly higher than those in patients with negative Hr-HPV (patients with CIN history, 0.7%; patients without CIN history, 0.1%; P = 0.002). The incidence of VaIN in patients with CIN history with HPV-16 infection after hysterectomy was as high as 50%, but in patients without CIN history, the incidences of different Hr-HPV subtypes were not significantly different (P = 0.953)., Conclusion: Patients with CIN history were more prone to VaIN and SCC after hysterectomy than were patients without CIN history. Patients should be screened thoroughly for cervical and vaginal lesions before hysterectomy. After hysterectomy, patients with CIN history should undergo lifetime annual LCT and HPV screening., (Copyright © 2020. Published by Elsevier Inc.)

The incidence of vaginal intraepithelial neoplasia (VAIN) is increasing annually; however, the reported values are likely underestimated. Risk factors for VAIN include advanced age, human papillomavirus (HPV) infection, history of hysterectomy, and simultaneous or previous cervical intraepithelial neoplasia (CIN) or cervical cancer cervical cancer. The most common presentation is abnormal cytology without clinical symptoms. Despite various treatment modalities available, the rate of disease recurrence is high, and its malignant potential has been documented. This study aimed to examine demographic and clinical characteristics and associated treatment outcomes of patients with VAIN. We retrospectively reviewed clinicopathologic data and clinical outcomes of patients diagnosed with VAIN at a single center between January 2010 and December 2017. Overall, 118 patients were included (average age 49.81 ± 9.77 years; range, 26-70 years). The distribution of the histologic grade was as follows: VAIN1, 30.5%; VAIN2, 41.5%; and VAIN3, 28.0%. In total, 97 (82.2%) patients had either prior or simultaneous cervical lesions, CIN (35.6%), or cervical cancer (55, 46.6%). A total of 100 cases (84.7%) were diagnosed using colposcopy and 18 (15.3%) were diagnosed by pathological accident after hysterectomy. Thin-prep cytology test (TCT) results were available for 112 (94.9%) patients, and 111 (94.1%) patients had abnormal cytology findings. Most patients were confirmed as HPV positive (115, 97.5%), and 84 (71.2%) patients were confirmed as positive for high-risk HPV types. Forty-two (35.6%) patients underwent hysterectomy before VAIN diagnosis, and the median interval between hysterectomy and VAIN diagnosis was 26.5 (range: 3-68) months. Most surgical indications were HPV-related diseases (34, 80.9%), such as CIN (8, 19.0%) or cervical cancer (26, 61.9%). Eight patients had no history of cervical lesions. A total of 100 patients underwent initial treatment. During the median follow-up period of 29 (range: 9-96) months, 78 (78%) patients experienced disease remission after initial treatment, 7 (7%) experienced disease recurrence, 10 (10%) had persistent disease, and 5 (5%) had progressive disease. Finally, two patients developed vaginal cancer without death. Colposcopy should be performed before vaginal hysterectomy for VAIN, particularly HPV-related cases. The incidence of VAIN was 20% after hysterectomy owing to non-HPV-related lesions; thus, this part of the screening should not be discontinued. VAIN grade 2,3 and VAIN associated with CIN or cervical cancer are disease types more likely to recur and progress to invasive cancer; active medical intervention is recommended., (© 2021 Japan Society of Obstetrics and Gynecology.)

Background: Rhabdomyosarcoma (RMS) of the female genitourinary tract (FGU-RMS) located at the vagina or uterus is one of the most favorable RMS sites. Little is known about treatment and outcome in infants and relapsed disease (RD)., Methods: Characteristics, treatment, and outcome of 71 children with FGU-RMS registered within five Cooperative Weichteilsarkom Studiengruppe (CWS) trials and one registry (1981-2019) were evaluated., Results: FGU-RMS was diagnosed in 67 patients with localized disease (LD) at a median age of 2.89 years (0.09-18.08). Multimodal treatment consisted of chemotherapy (CHT) (n = 66), secondary surgery (n = 32), and radiotherapy (n = 11). Age at diagnosis ≤12 months was the only significant negative prognostic factor influencing the event-free survival (EFS). Ten-year EFS and overall survival (OS) for infants ≤12 months were 50% and 81%, respectively. In contrast, children with LD >1 year and ≤10 years had a 10-year EFS and OS of 78% and 94% (P = .038), and >10 years of 82% and 88%, respectively (P = .53). Metastatic disease was observed in four patients of which three are alive. RD occurred in five of 12 infants ≤1 year and 10/55 children at a median of 1.38 years (0.53-2.97) after initial diagnosis. Treatment of patients with RD consisted of multimodal treatment (n = 13) or resection only (n = 2). Nine patients (60%) were alive in clinical remission at a median of 7.02 years (1.23-16.72) after diagnosis of RD., Conclusion: Infants with FGU-RMS have a higher relapse rate than older children with FGU-RMS, but prognosis is fair., (© 2021 Wiley Periodicals LLC.)

Aim: The human papilloma virus has been associated with anal, cervical, vaginal, and penile cancers. The primary aim of this population-based study is to determine whether HPV-associated cancers are more commonplace in patients with inflammatory bowel disease (IBD)., Method: The Hospital Episode Statistics (HES) database from 1997 to 2012, linked with officer for age standardized rates (ASR), were calculated using population data, and Cox regression analysis was used to determine whether IBD patients have poorer survival compared with non-IBD patients., Results: A total of 61,648 patients were included in this study; of these, 837 patients had a preexisting diagnosis of IBD (1.4%). Inflammatory bowel disease patients had a significantly higher ASR of anal cancers than the non-IBD population: 5.5 per 100,000 in the IBD group compared with 1.8 in the non-IBD group. The IBD group was also diagnosed with anal cancers at a younger age (60 years compared with 66 years in the non-IBD group, P < 0.001). The survival of IBD patients with anal cancer was also poorer than the non-IBD group (hazard ratio, 1.32; 95% confidence interval, 1.15-1.52; P < 0.001). On average, survival was significantly shorter in the IBD group with anal cancer (46 months) compared with the non-IBD group (61 months, P < 0.001). Age standardized rates for cervical cancer was significantly higher in the IBD group (5.2 of 100,000) compared with the non-IBD group (4.6 of 100,000 P = 0.042)., Conclusion: Patients with IBD have a higher rate of anal cancer compared with the general population. Survival is also worse for anal cancers in the IBD group., (© 2020 Crohn’s & Colitis Foundation. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Vaginal lesions are rare and of various types in children. Clinical presentation is generally undifferenciated. Histological examination is fundamental to ascertain the nature of the lesion. Regarding tumoral lesions, histological subtypes encountered are radically different from those seen in adults, dominated by stromal benign lesions., Objective: The aim of this retrospective study was to describe characteristics and pathological aspects of pediatric vaginal lesions, diagnosed in a single pediatric experienced center., Study Design: A database analysis was performed on all vaginal samples of patients under 18 years old received in a pediatric-specialized pathology laboratory of an academic hospital, over a 26-year period., Results: Among 36 vaginal tissue samples reported, a total of 15 tumoral or pseudotumoral processes was recorded. Primitive malignant tumors included embryonal rhabdomyosarcoma (n = 3) and germ-cell tumors, yolk-sac type (n = 2). Benign tumoral or pseudotumoral processes included inflammatory stromal polyps (n = 8), epidermic cyst (n = 1), and benign Müllerian papilloma (n = 1)., Discussion: Over 15 primitive vaginal tumors, 1/3 was malignant with embryonal rhabdomyosarcoma being the most common. The remaining 2/3 specimens were benign, with stromal inflammatory lesions being the most commonly observed. Fibro-epithelial polyp is a debated entity, which covers a wide histological spectrum, with varying inflammation and stromal cellularity, raising sometimes the question of the differential diagnosis with rhabdomyosarcoma. Stromal cells morphology along with their immunohistochemical profile suggest their reactive myofibroblastic nature. Pseudotumoral inflammatory lesions display very similar histological findings with these entities. A common pathogenesis beginning with an inflammatory process, potentially accelerated by chronic traumatic factors, could be discussed., Conclusion: We confirmed the rarity and the diversity of vaginal lesions in children. Vaginoscopy and biopsy sample should be systematic, given the non-specific presentation of tumoral processes. Myogenin immunostain must be systematic in case of vaginal polypoid mass, in order to rule out malignancy., Competing Interests: Conflict of interest The Authors declare that there is no conflict of interest., (Copyright © 2020 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

Vulvar and vaginal cancers are relatively rare cancers, together responsible for less than 1% of the global cancer incidence among women in 2018. The majority of vaginal cancers and a lesser proportion of vulvar cancers are associated with HPV, with rising incidence rates of vulvar cancer observed in younger women, possibly due to an increased prevalence of high-risk HPV types. This report assesses recent international variations in the incidence rates of vulvar and vaginal cancer derived from high-quality data from population-based cancer registries in 68 countries, and further assesses time trends for selected longer-term series in eight countries (Australia, China, Colombia, India, Norway, Slovakia, the U.S., and the U.K.) over the period 1983 to 2012. We observed a 30-fold variation in the recorded incidence rates of vulvar cancer in contrast with the threefold variation for vaginal cancer. We also observed a rising incidence of vulvar cancer in Australia, Norway and the U.K., and Slovakia, with a more rapid rise in the rates seen in women aged < 60 years at diagnosis. The annual percentage change over the most recent decade varied from 1.7% in Norway to 4.1% in Slovakia. The increases are largely confined to younger women and are likely linked to generational changes in sexual behaviour (earlier age at sexual debut and increasing transmission of HPV among cohorts born 1940 to 1950 and thereafter. Vaginal cancer incidence rates, in contrast, were lower and more stable, despite the higher HPV-attributable fraction relative to vulvar cancer. Irrespective of the trends, an increasing number of women are predicted to be diagnosed worldwide with both cancer types in future decades as population ageing and growth continues. The promise of high-coverage HPV vaccination will likely counter this rising burden, but the impact may take a number of decades., (© 2020 UICC.)

Objectives: The aim of this survey was to evaluate the different surgical approaches for women with high-grade vaginal intraepithelial neoplasia (HG-VaIN) used in 8 hospitals in central and northern Italy in the last 20 years. In particular, the baseline characteristics of the patients and factors potentially leading to excisional treatment rather than ablation were considered. Moreover, the clinical outcome of patients treated for HG-VaIN (disease persistence or recurrence and progression toward invasive vaginal cancer) was analyzed., Materials and Methods: The medical records of all women initially diagnosed with HG-VaIN and subsequently treated in 8 Italian hospitals from January 1996 to December 2016 were analyzed in a multicenter retrospective case series., Results: Among the 226 women included, 116 (51.3%) underwent ablative procedures and 110 underwent excisional surgery (48.7%). An ablative procedure was preferred in cases where multiple lesions were found on colposcopic examinations. Physicians decided more frequently to perform excisional procedures in women with menopausal status, high-grade referral cervical cytology, previous hysterectomy for human papillomavirus-related disease, or VaIN 3 on colposcopic-guided biopsy., Conclusions: The surgical treatment of HG-VaIN should be tailored according to the clinical characteristics of each woman and each lesion. However, in potentially high-risk cases (VaIN 3, previous hysterectomy for human papillomavirus-related disease, and menopausal women) or in those cases in which an occult invasive disease cannot be ruled out, an excisional approach should be preferred.In any case, long-term follow-up is advisable in women treated for HG-VaIN.

Objective: To describe trends in incidence of high-grade vaginal intraepithelial neoplasia (VaIN) and vaginal squamous cell carcinoma (SCC) in Denmark. For vaginal SCC, we also examine 5-year relative survival and mortality., Methods: All high-grade VaIN cases diagnosed 1997-2017 and vaginal SCCs during 1978-2017 were identified in two high-quality nationwide registers. Age-standardized incidence rates and average annual percentage change (AAPC) were assessed. For vaginal SCC, 5-year relative survival was calculated, and Cox regression was applied to study the effect of selected characteristics on mortality., Results: Altogether, 831 cases of high-grade VaIN and 721 vaginal SCCs were identified. The age-standardized incidence rate of high-grade VaIN showed no clear trend over time. However, when we stratified by age and divided the study period according to HPV vaccine licensure in Denmark (2006), the incidence of high-grade VaIN decreased significantly by 15.6% per year (95% CI: -23.2, -7.3%) after 2007 onwards among the youngest women (<30 years). For vaginal SCC, the incidence decreased from 0.5 (1978-1982) to 0.3 (2013-2017) per 100,000 woman-years. The 5-year relative survival improved over time and was 67.9% (95% CI: 54.9, 84.1%) in the most recent time period. Mortality was significantly associated with calendar year, age, and stage at diagnosis., Conclusions: The overall incidence of high-grade VaIN showed no clear trend over time, but a significant decline was observed in women younger than 30 years after HPV vaccine licensure. The incidence of vaginal SCC was reduced by approximately 50% and survival after vaginal SCC improved over time., Competing Interests: Declaration of competing interest Susanne K. Kjaer has previously received speaking and advisory board fees from Merck, and research grant through her institution from Merck. Hanna Kristina Bertoli, Louise Baandrup, Gitte Lerche Aalborg, Alexander K. Kjaer and Louise T. Thomsen report no potential conflicts of interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Women with cervical intraepithelial neoplasia grade 3 (CIN3) have a long-lasting increased risk for noncervical high-risk human papillomavirus (hrHPV)-related (pre)malignancies. The aim of our study was to estimate this risk in women with recurrent CIN3 compared to women without a history of CIN3 and women with a single episode of CIN3. Women with a CIN3 diagnosis between 1990 and 2010 were obtained from the Dutch Pathology Registry (PALGA) and matched with a control group of women without CIN3. Analysis has been conducted in a subset of women with recurrent CIN3, defined as reoccurrence minimally 2 years post-treatment. Cases of noncervical hrHPV-related (pre)malignancies of the anus, vulva, vagina and oropharynx were identified until 2015 and incidence rate ratios (IRRs) were estimated. Then, 1,797 women with recurrent CIN3 were included with a median age of 34 years (range 18-76) and 31,594 person-years of follow-up. Women with recurrent CIN3 had an increased risk of developing noncervical hrHPV-related (pre)malignancies compared to women without CIN3 with an IRR of 25.96 (95%CI 6.32-106.58). The IRR was 2.48 (95% CI 1.87-3.30) compared to women with a single episode of CIN3. Studies on posttreatment follow-up and prophylactic hrHPV vaccination are warranted., (© 2019 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

Background: Human papillomavirus (HPV) is associated with a significant public health burden, yet few studies have been conducted in Asia, especially on noncervical cancers. We estimated the incidence and cost of oropharyngeal and noncervical anogenital (anal, vulvar, vaginal, penile) cancer in Korea., Methods: We conducted a retrospective cohort study using Korea's National Health Insurance (NHI) claim database from 2013 to 2016. The main outcome measures were the number of respective cancer incidences during the study period and the annual costs per patient in the first year after diagnosis, which was adjusted by relevant variables based on the regression analysis., Results: During the study period, 8022 patients with these cancers were identified, and oropharyngeal cancer comprised 46% of them. The crude incidence rate for male oropharyngeal cancer was significantly higher than that of females (3.1 vs. 0.7 per 100,000 as of 2016, respectively). Additionally, the crude incidence of male oropharyngeal cancer increased from 2.7 in 2013 to 3.1 in 2016, whereas that of female and other cancers was stable during the study period. The mean annual incidence-based cost per patient in 2016 was highest for oropharyngeal cancers (21,870 USD), and it was significantly higher in males than in females based on then regression analysis (p < .001)., Conclusions: Oropharyngeal cancer comprises the highest number of HPV-associated noncervical cancer incidences in Korea, and the incidence and cost of oropharyngeal cancer was significantly higher among males than females. More aggressive public health policy toward males may decrease gender gap of oropharyngeal cancer.

Background: Women with human immunodeficiency virus have higher rates of abnormal cervical and vaginal cytology and, subsequently, of cervical and vaginal cancers. Although professional bodies currently advocate for indefinite cytology screening for women living with human immunodeficiency virus, these recommendations are based on expert opinion, not evidence-based. In the general population, women who have never had an abnormal cytology result can cease screening at age 65 years. This is due to the relatively low incidence of dysplasia in this group and the risk of false-positive results as women age, invasive follow-up testing, and destructive treatments of lesions that are unlikely to progress to cancer. What is unclear, however, is how human immunodeficiency virus-infected women over age 65 years who have no history of abnormal cytology should be screened to maximize benefit while reducing harms of overscreening. This is a crucial question, as women over age 65 years who are living with human immunodeficiency virus comprise a rapidly growing population., Objective: To describe the incidence of abnormal cervical and vaginal cytology results in women over the age of 65 years living with human immunodeficiency virus, with the goal of providing evidence for screening recommendations., Materials and Methods: A retrospective chart review was performed, identifying 69 women who received gynecologic follow-up in a county hospital system in Houston, Texas, between 2000 and 2018 and who met study criteria. Incidence of abnormal cytology after age 65 was determined by analyzing all available cytology results after age 65. Demographic and clinical risk factors, including human immunodeficiency virus-specific clinical risk factors, were analyzed. Matched cervical and vaginal pathology results, if conducted, were also evaluated. Statistical analyses were conducted using Stata 15, including χ 2 tests and Wilcoxon rank-sum tests for categorical and continuous variables, respectively. Estimates of the cumulative probability of developing an abnormal cytology result was calculated using the Kaplan-Meier method., Results: Among 69 women with no history of abnormal cervical cytology, 12 (17%) went on to develop abnormal cytology results, including 3 (4%) showing high-grade squamous intraepithelial lesions. The incidence rate was 3.5 cases per 100 woman-years (95% confidence interval, 1.58, 7.81). No demographic or gynecologic characteristics were associated with abnormal cytology. A CD4 count of <200 at the time of human immunodeficiency virus diagnosis or at the time of cytology was associated with an abnormal Papanicolaou test result (P < .0001, P = .031). Of women with pathology results in the county hospital system (n = 8), 4 (50%) had cervical intraepithelial neoplasia 2+ or vaginal intraepithelial neoplasia 2+. No women developed invasive cancer. However, 50% of women who had an abnormal Papanicolaou test result in the study period were lost to follow-up; outcomes for these patients are unknown., Conclusion: Given the relatively high proportion (4%) of women with high-grade squamous intraepithelial lesions/cervical intraepithelial neoplasia 2+/vaginal intraepithelial neoplasia 2+ during the study period, we agree with current screening recommendations for continued routine Papanicolaou testing after the age of 65 years in women with human immunodeficiency virus. More evidence from larger studies is needed to solidify evidence-based screening recommendations in this unique and growing population., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objectives: All cervical cancers and some vulvar, vaginal and anal cancers are caused by high-risk human papillomavirus (hrHPV). However, little is known about the association between cervical HPV infection and subsequent intraepithelial neoplasia and cancer at other anogenital sites. In this prospective cohort study, we estimated the risk of vulvar, vaginal and anal intraepithelial neoplasia grade 2/3 or cancer (VIN2+, VaIN2+, AIN2+) according to cervical hrHPV status., Methods: Liquid-based cervical cytology samples were collected from 40,399 women screened against cervical cancer in Copenhagen, Denmark, during 2002-2005. Samples were tested for hrHPV using Hybrid Capture 2 (HC2) and genotyped using INNO-LiPA. We linked the cohort with Danish nationwide registries to identify cases of VIN2+, VaIN2+ and AIN2+ during up to 15 years of follow-up. We estimated age-adjusted hazard ratios (HRs) using Cox regression and cumulative incidences using Aalen-Johansen's estimator., Results: Women with cervical HPV16 infection had increased hazard of VIN2+ (HR = 2.6; 95% confidence interval [CI], 1.2-5.5), VaIN2+ (HR = 23.5; 95% CI, 6.8-81.6) and AIN2+ (HR = 3.7; 95% CI, 1.1-12.2) compared with HC2 negative women. Women with other hrHPV types than HPV16 also had increased hazard of VaIN2+ (HR = 7.1; 95% CI, 2.3-22.3) and a borderline statistically significantly increased risk of AIN2+ (HR = 2.2; 95% CI, 0.9-4.9) compared with HC2 negative women. The 10-year cumulative incidences of VIN2+, VaIN2+ and AIN2+ in women with cervical HPV16 were 0.3% (95% CI, 0.2%-0.7%), 0.2% (95% CI, 0.1%-0.5%) and 0.1% (95 CI, 0.0%-0.4%)., Conclusions: Cervical HPV16 infection is associated with increased risk of VIN2+, VaIN2+ and AIN2+., Competing Interests: Declaration of competing interest Susanne K. Kjær has received speaker's and advisory board fees from Merck, and unrestricted research grant through her institution from Merck. Thomas Iftner has received lecture fees and research grants through his institution from Hologic GmbH and Becton Dickinson GmbH. Hanna Kristina Bertoli, Louise T. Thomsen and Christian Dehlendorff report no potential conflicts of interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Human papillomavirus (HPV) infection is a pre-requisite for cervical cancer, which represents the third most common cancer among women worldwide. A causal relationship also exists between HPV and cancer in other areas of the female reproductive system including the vagina and vulva. Whilst the incidence of vaginal cancer in the UK has remained relatively stable over the past 25 years, vulval cancer rates are increasing. A body of literature exists on the epidemiology and aetiology of vaginal and vulval cancer, but little is known about the economic burden. The objective of this study was to quantify the costs of treating these cancers on the National Health Service (NHS) in England., Methods: Inpatient and outpatient episodes were derived from Hospital Episode Statistics (HES). Health Resource Group (HRG) tariffs and National Reference Costs were used to estimate the cost of treating pre-cancerous and invasive vaginal and vulval lesions in England., Results: The study showed that for the 5 years from 2009/2010 to 2014/2015 the total cost associated with pre-cancerous and invasive vaginal and vulval lesions was over £14 million per year on average (95% of which was attributed to inpatient costs). Vulval cancer accounted for the largest proportion; an estimated 60% of the total cost (£8.82 million). On average 4316 patients per year in England were admitted to hospital and 912 patients attended outpatient settings for pre-cancerous and invasive disease of the vagina and vulva., Conclusion: The results indicate that vaginal and vulval cancer cost the English health care system over £14 million per year. Given the causal role of HPV in a proportion of these cancers, preventative measures such as the national HPV immunisation programme have the potential to reduce the economic burden. To ensure optimal use of NHS resources, it is important that future economic evaluations of such preventative measures consider the full burden of HPV related disease.

The study aim was to describe human papillomavirus (HPV)-attributable cancer burden in Rwanda, according to anogenital cancer site, HPV type, age and HIV status. Tissue specimens of cervical, vulvar, vaginal, penile and anal cancer diagnosed in 2012-2018 were retrieved from three cancer referral hospitals and tested for high-risk (HR) HPV DNA. Cervical cancer represented the majority of cases (598 of 738), of which 96.0% were HR-HPV positive. HPV-attributable fractions in other cancer sites varied from 53.1% in 81 penile, through 76.7% in 30 vulvar, 83.3% in 24 vaginal, up to 100% in 5 anal cases. HPV16 was the predominant HR-HPV type in cervical cancer (55.0%), followed by HPV18 (16.6%) and HPV45 (13.4%). HPV16 also predominated in other cancer sites (60-80% of HR-HPV-attributable fraction). For cervical cancer, type-specific prevalence varied significantly by histology (higher alpha-9 type prevalence in 509 squamous cell carcinoma vs. higher alpha-7 type prevalence in 80 adenocarcinoma), but not between 501 HIV-negative and 97 HIV-positive cases. With respect to types targeted, and/or cross-protected, by HPV vaccines, HPV16/18 accounted for 73%, HPV31/33/45/52/58 for an additional 22% and other HR-HPV types for 5%, of HPV-attributable cancer burden, with no significant difference by HIV status nor age. These data highlight the preventive potential of the ongoing national HPV vaccination program in Rwanda, and in sub-Saharan Africa as a whole. Importantly for this region, the impact of HIV on the distribution of causal HPV types was relatively minor, confirming type-specific relevance of HPV vaccines, irrespective of HIV status., (© 2019 International Agency for Research on Cancer (IARC/WHO); licensed by UICC.)

Vaginal intraepithelial neoplasia (VAIN) is often found by chance. We investigated the prevalence of VAIN and related human papillomavirus (HPV) types in comparison with cervical intraepithelial neoplasia (CIN). This study enrolled 648 women who were referred to the outpatient clinic of Kanazawa Medical University Hospital for abnormal cytology from January 2009 to January 2019. HPV genotypes were determined using Genosearch-31 + 4, which can detect 35 different HPV types. Colposcopy was performed at the first visit by an experienced gynecological oncologist. Among 611 subjects with squamous cell lesions, 107 (17.5%) VAIN cases were identified, and 67 (11.0%) women had both VAIN and CIN. Ultimately, 72 VAIN1, 15 VAIN2/3, 203 CIN1, 249 CIN2/3, 32 cervical squamous cell carcinomas (SCC), and one vaginal SCC (Vag-SCC) were identified. The prevalences of VAIN1, VAIN2/3, and Vag-SCC were 35.5%, 6.0%, and 3.1% of equivalent cervical lesions, respectively. The VAIN patients were older than the CIN patients (P = .002). About half of the VAIN cases were diagnosed during the follow-up. Multiple HPV infections were found in 42.9% of the VAIN and CIN patients. HPV52, 16, 51, 53, and 56 were the most common types in VAIN, whereas HPV16, 52, 58, 51, and 31 predominated in CIN. HPV18 was rare in VAIN, HPV58 was more common in CIN than in VAIN, and HPV53 and HPV73 were more common in VAIN. In conclusion, VAIN1 was identified more frequently than we expected. Various HPV types were identified in the vagina, which is likely a reservoir for HPV., (© 2019 Wiley Periodicals, Inc.)

Objective: To study the risk of vaginal cancer among hysterectomised women with and without cervical intraepithelial neoplasia (CIN)., Design: Population-based national cohort study., Setting and Population: All Swedish women, 5 million in total, aged 20 and up, 1987-2011 using national registries., Methods: The study cohort was subdivided into four exposure groups: hysterectomised with no previous history of CIN3 and without prevalent CIN at hysterectomy; hysterectomised with a history of CIN3/adenocarcinoma in situ (AIS); hysterectomised with prevalent CIN at hysterectomy; non-hysterectomised., Main Outcome Measure: Vaginal cancer., Results: We identified 898 incident cases of vaginal cancer. Women with prevalent CIN at hysterectomy and those with a history of CIN3/AIS had incidence rates (IR) of vaginal cancer of 51.3 (95% CI 34.4-76.5) and 17.1 (95% CI 12.5-23.4) per 100 000, respectively. Age-adjusted IR-ratios (IRRs) compared with hysterectomised women with benign cervical history were 21.0 (95% CI 13.4-32.9) and 5.81 (95% CI 4.00-8.43), respectively. IR for non-hysterectomised women was 0.87 (95% CI 0.81-0.93) and IRR was 0.37 (95% CI 0.30-0.46). In hysterectomised women with prevalent CIN, the IR remained high after 15 years of follow up: 65.7 (95% CI 21.2-203.6)., Conclusions: Our findings suggest that hysterectomised women with prevalent CIN at surgery should be offered surveillance. Hysterectomised women without the studied risk factors have a more than doubled risk of contracting vaginal cancer compared with non-hysterectomised women in the general population. Still, the incidence rate does not justify screening., Tweetable Abstract: High risk of contracting vaginal cancer among hysterectomised women having prevalent CIN at surgery., (© 2019 Royal College of Obstetricians and Gynaecologists.)

Immunosuppressive drugs are the cornerstone in the treatment of inflammatory bowel disease (IBD), however they are associated with an increased risk of extra-intestinal cancer. Whether the risk for female genital tract malignancies, including vulvar and vaginal cancer, is increased is less clear. Our aim was to investigate the risk of these malignancies in IBD-patients. Histopathological data of all IBD patients with a vulvar or vaginal (pre-)cancerous lesion were retrieved from the Dutch nationwide network and registry of histopathology and cytopathology from 1991 to 2015. Medical history was retrieved from patient records. Data from the Central Office for Statistics, the Dutch comprehensive cancer organization, and the IBDSL cohort were obtained to calculate the standardized, and age-adjusted incidence rates. Fifty-five patients met the inclusion criteria. A standardized incidence rate of 1.2(95% CI:0.8-1.7) for vulvar and vaginal carcinoma among adult female IBD was calculated, which did not significantly differ from the general population. The use of immunosuppressive therapy did not increase the occurrence of vulvovaginal malignancy, nor did it influence the recurrence rate. However, immunosuppressive drugs ever-users were on average 11 years younger at the time of their gynaecological diagnosis. Overall, our data do not support intensified screening for vulvar or vaginal malignancies in female IBD patients., (Copyright © 2019 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Introduction: Chronic infections and infestations represent one of the leading causes of cancer. Eleven agents have been categorized by the International Agency for Research on Cancer (IARC) in Group 1, 3 in Group 2A and 4 in Group 2B. We previously estimated that the incidence of cancers associated with infectious agents accounted for the 8.5% of new cancer cases diagnosed in Italy in 2014., Methods: In the present study we evaluated the incidence of cancer in Italy and in the 20 Italian regions in 2018, based on the data of Cancer Registries, and calculated the fraction attributable to infectious agents., Results: Cancers of infectious origin contributed to the overall burden of cancer in Italy with more than 27,000 yearly cases, the 92% of which was attributable to Helicobacter pylori, human papillomaviruses, and hepatitis B and C viruses. With the exception of papillomavirus-related cancers, the incidence of cancers of infectious origin was higher in males (16,000 cases) than in females (11,000 cases). There were regional and geographical variations of cancers depending on the type of cancer and on the gender. Nevertheless, the overall figures were rather similar, the infection-related cancers accounting for the 7.2, 7.6, and 7.1% of all cancers in Northern, Central, and Southern Italy, respectively., Conclusions: The estimate of the incidence of cancers attributable to infectious agents in Italy in 2018 (7.3% of all cancer cases) is approximately half of the worldwide burden, which has been estimated by IARC to be the 15.4% of all cancer cases in 2012., (©2019 Pacini Editore SRL, Pisa, Italy.)

Human papillomavirus (HPV) causes nearly all cervical cancers and some cancers of the vagina, vulva, penis, anus, and oropharynx (1).* Most HPV infections are asymptomatic and clear spontaneously within 1 to 2 years; however, persistent infection with oncogenic HPV types can lead to development of precancer or cancer (2). In the United States, the 9-valent HPV vaccine (9vHPV) is available to protect against oncogenic HPV types 16, 18, 31, 33, 45, 52, and 58 as well as nononcogenic types 6 and 11 that cause genital warts. CDC analyzed data from the U.S. Cancer Statistics (USCS) † to assess the incidence of HPV-associated cancers and to estimate the annual number of cancers caused by HPV, overall and by state, during 2012-2016 (3,4). An average of 43,999 HPV-associated cancers were reported annually, and an estimated 34,800 (79%) of those cancers were attributable to HPV. Of these 34,800 cancers, an estimated 32,100 (92%) were attributable to the types targeted by 9vHPV, with 19,000 occurring among females and 13,100 among males. The most common were cervical (9,700) and oropharyngeal cancers (12,600). The number of cancers estimated to be attributable to the types targeted by 9vHPV ranged by state from 40 to 3,270 per year. HPV vaccination is an important strategy that could prevent these cancers, but during 2018, only half of adolescents were up to date on HPV vaccination (5). These surveillance data from population-based cancer registries can be used to inform the planning for, and monitor the long-term impact of, HPV vaccination and cancer screening efforts nationally and within states., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. No potential conflicts of interest were disclosed.

Data on familial risks in penile and vulvar/vaginal cancers and in second primary cancers (SPCs) following these cancers are limited. We used the Swedish Family-Cancer Database from years 1958 through 2015 to identify 3641 penile and 8856 vulvar/vaginal cancers and to calculate relative risks (RRs) and 95% confidence intervals (CIs) for these cancers according to site-specific cancer in family members; additionally risk for SPCs was calculated. The familial RR for concordant (same) penile cancer was 3.22 (1.34-7.74), and it was 2.72 (1.69-4.39) for vulvar/vaginal cancer; RRs were increased for vulvar/vaginal cancer in families of anal cancer patients. RR for second penile cancer after penile cancers was 11.68 (7.95-17.18), while that for concordant vulvar/vaginal cancer was 9.03 (7.31-11.15). SPCs were diagnosed in 16.8% of penile cancer patients and in them 45.9% of deaths were caused by SPC (other than penile cancer). In vulvar/vaginal cancer patients with SPC, 36.4% of deaths were due to SPC. The results showed that these genital cancers might run in families and as SPCs are associated with human papilloma virus and smoking related cancers. Risk for these genital and anal SPCs are high and a follow-up plan should be agreed at diagnosis of these cancers.

Gestational trophoblastic disease (GTD) develops from abnormal cellular proliferation of trophoblasts following fertilization. It includes benign trophoblastic disease (hydatidiform moles (HM)) and the malignant trophoblastic diseases or gestational trophoblastic neoplasia (GTN). The frequency of the GTD in Tunisia is one per 918 deliveries. The aim of this study is to analyze the clinical characteristics, treatment and outcomes of GTD at Salah Azaiez Institute (ISA). Medical records of women diagnosed with GTD at ISA from January 1 st , 1981 to December 31 st , 2012 were retrospectively reviewed. FIGO score was determined retrospectively for patients treated before 2002. One hundred and nine patients with GTN were included. Patients presented with metastases at 43% of cases. The most common metastatic sites were lung (30%) and vagina (13%). Fifty six (56 (51%) patients had low-risk and 21 (19%) cases had high-risk, the FIGO score was not assessed in 32 cases. After a median follow-up of 46 months, 21 patients were lost to follow-up, 12 patients died, 19 progressed and 8 relapsed. At 10 years, the OS rate was 85% and the PFS rate 79%. OS was significantly influenced by the presence of metastases at presentation (M0 100 % vs. Metastatic 62 %; p < 0.0001), FIGO stage (I-II 100% VS 61% and 65% for stage III and IV; p < 0.001), FIGO score (low-risk 99 % vs. high-risk 78 %; p < 0.001). GTN is a significant source of maternal morbidity with increased risk of mortality from complications if not detected early and treated promptly., Competing Interests: The authors declare no competing interests.

Background: Human papilloma virus (HPV) associated cervical cancer remains a global concern particular, in Sub-Saharan Africa (SSA) where the impact is felt most. Evidence show that many other cancers such as vaginal, anal, oropharyngeal, penile are because of persistent infection with HPV especially, high-risk types., Aim: We mapped evidence on the incidence, prevalence, mortality, and the trends of human papillomavirus-related cancers in SSA., Methods: A comprehensive literature search was conducted from several databases including PubMed, Google scholar, Science Direct, and CINAHL and MEDLINE via EBSCOhost as well as World Health Organization website for grey literature. Studies reporting HPV-related cancers in SSA outcomes including prevalence, incidence, mortality, and trends were included in this study. The risk of bias of the included studies were assessed using the mixed methods appraisal tool version 2011. We employed PRISMA (preferred reporting items for systematic reviews and meta-analyses) to report the search results. Thematic analysis used to reveal the emerging themes from the included studies., Results: Seventy-four (74) studies were retrieved at full article screening, eight of them (six reviews, and two quantitative study) were eligible for data extraction. The degree of agreement between the two independent reviewers following full article screening, was 86.49% agreement versus 64.57% likely by chance which constituted moderate to significant agreement (Kappa statistic = 0.62, p-value< 0.05). Of the eight included studies, four (50%) studies generalized about SSA with no country of interest; two (25%) studies were conducted in Nigeria; one (12.5%) reported about Uganda, Zambia, Guinea, Malawi Tanzania, Mali, Mozambique, Zimbabwe; and one (12.5%) reported about Ethiopia, Senegal, Zimbabwe and Uganda. These eight included studies reported evidence on more than one outcome of interest. Four studies reported about the prevalence of HPV-related cancers, seven studies reported about the incidence, four studies reported about mortality, and four studies reported about the trends of HPV-related cancers., Conclusion: This study observation highlighted a gap of knowledge regarding the epidemiological data on the recent HPV prevalence in SSA, which will have a potential impact in determining the distribution of HPV on different body sites (cervix, penis, vagina, vulva, anus and oropharynx). Ongoing research projects are recommended in SSA to enhance the value of HPV, and HPV-associated cancers epidemiological data to inform strategies or/and policies on prevention, diagnosis, and treatment of HPV-related conditions.

Objectives: To determine from the perspective of the State of Texas, the direct medical care costs associated with cervical, vaginal, and vulvar cancers in Texas Medicaid enrollees., Materials and Methods: We conducted a case-control study and searched Texas Medicaid databases between 2008 and 2012 for eligible cancer patients. A comparison group was selected for each cancer site using a 2-step 1:1 propensity score matching method. Patients were followed for 2 years after cancer diagnosis to estimate monthly and yearly direct medical costs. For each cancer site, the differential cost between patients and the matched comparison individuals was the estimated cost associated with cancer., Results: The study included 583 cervical, 62 vaginal, and 137 vulvar cancer patients and equal numbers of cancer-free comparison individuals. Among the cases, 322 cervical cancer patients, 46 vaginal cancer patients, and 102 vulvar cancer patients were Medicaid-Medicare dual eligible enrollees. For Medicaid-only enrollees, the adjusted first- and second-year mean total differential costs were US $19,859 and $3,110 for cervical cancer, US $19,627 and $4,582 for vaginal cancer, and US $7,631 and $777 for vulvar cancer patients, respectively. For Medicaid-Medicare dual eligible enrollees, adjusted first- and second-year mean total differential costs incurred by Medicaid were US $2,565 and $792 for cervical cancer, US $1,293 and $181 for vaginal cancer, and US $1,774 and $1,049 for vulvar cancer patients, respectively., Conclusions: The direct medical costs associated with cervical, vaginal, and vulvar cancers in Texas Medicaid were substantial in the first 2 years after cancer diagnosis, but dual eligibility for Medicare coverage attenuated Medicaid costs.

Background: High-risk human papilloma viruses (HPV) are a causative agent of anogenital and oropharyngeal cancers. Patients treated for a preinvasive or invasive HPV-associated cancer may be at increased risk of a second such malignancy., Methods: We performed a systematic review and random effects meta-analysis to estimate the risk of HPV-associated cancer after prior diagnosis. Studies reporting second cancers at anogenital and oropharyngeal sites after prior diagnoses (preinvasive/invasive HPV-associated cancer) were identified. Studies reporting standardised incidence ratios (SIRs) were included in formal meta-analyses of second cancer risk. (PROSPERO ID: CRD42016046974)., Results: Searches returned 5599 titles, including 60 unique, eligible studies. Thirty-two (98 comparisons) presented SIRs for second cervical, anal, vulvo-vaginal, penile, and/or oropharyngeal cancers, included in the meta-analyses. All studies (and 95/98 comparisons) reported increased cancers in the population with previous HPV-associated cancer when compared to controls. Pooled SIRs for second primary cancers ranged from 1.75 (95% CI 0.66-4.67) for cervical cancer after primary anal cancer, to 13.69 (95% CI 8.56-21.89) for anal cancer after primary vulvo-vaginal cancer., Conclusions: We have quantified the increased risk of second HPV-associated cancer following diagnosis and treatment for initial cancer or preinvasive disease. This has important implications for follow-up, screening, and future therapeutic trials.

Importance: In the last 4 decades, survival among patients with human papillomavirus (HPV)-associated cancers has improved, while the incidence of these cancers has increased among younger cohorts. Among survivors of HPV-associated cancers, persistent HPV infection may remain a risk factor for preventable HPV-associated second primary cancers (HPV-SPCs)., Objectives: To investigate the risk of HPV-SPCs among survivors of HPV-associated index cancers and to test the hypothesis that the HPV-SPC risk among these persons has increased over the last 4 decades., Design, Setting, and Participants: A retrospective cohort study of 9 cancer registries of the Surveillance, Epidemiology, and End Results (SEER) database was conducted to identify patients with HPV-associated (cervical, vaginal, vulvar, oropharyngeal, anal, and penile) cancers diagnosed from January 1, 1973, through December 31, 2014. The dates of analysis were July 1, 2017, to January 31, 2018., Main Outcomes and Measures: The HPV-SPC risk was quantified by calculating standard incidence ratios (SIRs) and excess absolute risks (EARs) per 10 000 person-years at risk (PYR). The HPV-SPC risk by time was estimated using Poisson regression., Results: From 113 272 (73 085 female and 40 187 male) survivors of HPV-associated cancers, 1397 women and 1098 men developed HPV-SPCs. The SIRs for HPV-SPCs were 6.2 (95% CI, 5.9-6.6) among women and 15.8 (95% CI, 14.9-16.8) among men. The EARs were 18.2 per 10 000 PYR for women and 53.5 per 10 000 PYR for men. Among both women and men, those who had index oropharyngeal cancers had the highest HPV-SPC risk (SIR, 19.8 [95% CI, 18.4-21.4] and EAR, 80.6 per 10 000 PYR among women; SIR, 18.0 [95% CI, 16.9-19.1] and EAR, 61.5 per 10 000 PYR among men). Women who had index cervical cancers and men who had index anal cancers had the lowest HPV-SPC risk (SIR, 2.4 [95% CI, 2.2-2.7] and EAR, 4.5 per 10 000 PYR among women; SIR, 6.5 [95% CI, 4.7-8.8] and EAR, 18.5 per 10 000 PYR among men). Both women and men who had index HPV-associated cancers of any kind had a significantly higher risk of oropharyngeal HPV-SPCs. Over the last 4 decades, the risk of developing most types of HPV-SPCs after index cervical, vaginal, and vulvar cancers increased., Conclusions and Relevance: According to this study, the HPV-SPC risk among survivors of HPV-associated cancers is significant, implying that persistent HPV infection at multiple sites may be associated with HPV-SPCs. These findings have the potential to inform surveillance recommendations for survivors of HPV-associated cancers.

Objective: To examine incidences and risk factors for metachronous vulvar, vaginal, and anal malignancies after a cervical cancer diagnosis., Methods: This is a retrospective study examining data from the Surveillance, Epidemiology, and End Result Program between 1973 and 2013. Cumulative incidences of vulvar, vaginal, and anal cancers after the diagnosis of cervical cancer were assessed (n = 79,050). Multivariable analysis was performed to determine independent risk factors for these metachronous cancers., Results: Vaginal cancer (20-year cumulative incidence, 0.57%) was the most common type of metachronous malignancy, followed by vulvar cancer (0.33%), and anal cancer (0.16%, P < 0.001). Median time to diagnosis was 5.4 years for vaginal cancer, 6.5 years for vulvar cancer, and 13.5 years for anal cancer. On multivariable analysis, metachronous vulvar cancer was associated with older age (hazard ratio [HR] per year 1.04, 95% confidence interval [CI] 1.02-1.05, P < 0.001), squamous histology (HR 2.64, 95%CI 1.38-5.05, P = 0.003), and radiotherapy use (HR 2.52, 95%CI 1.66-3.84, P < 0.001); metachronous vaginal cancer was associated with older age (HR per year 1.03, 95%CI 1.02-1.04, P < 0.001) and Black race (HR 1.73, 95%CI 1.20-2.48, P = 0.003); and metachronous anal cancer was associated with older age (HR 1.03, 95%CI 1.01-1.05, P = 0.017). Overall survival of metachronous cancer was poor (5-year rates: 46.3% for vulvar, 43.0% for vaginal, and 47.5% for anal cancer, respectively)., Conclusion: Although rare, the rate of ano-genital cancers continues to increase over time after a cervical cancer diagnosis. Long-term follow-up and surveillance after cervical cancer treatment is therefore reasonable to detect these metachronous malignancies, particularly in those with risk factors., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: To estimate the proportion of vulvar and vaginal low-grade and high-grade squamous intraepithelial lesions (LSILs and HSILs) in females 15-26 years of age attributable to 14 human papillomavirus (HPV) genotypes (6, 11, 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59)., Methods: A post hoc analysis of prospectively diagnosed vulvar and vaginal LSILs and HSILs among females 15-26 years of age enrolled in the placebo arms of two phase 3, randomized HPV vaccine trials assessed 14 prespecified HPV genotypes associated with cervical cancers or anogenital warts using a type-specific multiplex polymerase chain reaction assay. The frequency of lesions associated with specific HPV genotypes was estimated by proportional and other attribution methods., Results: During approximately 4 years of follow-up in 8,798 females, 40 vulvar LSILs and 46 vulvar HSILs were diagnosed in 68 females, and 118 vaginal LSILs and 33 vaginal HSILs were diagnosed in 107 females. Females developing vulvar (41.2%) or vaginal (49.5%) lesions also had cervical lesions, whereas 6.5% of females with cervical lesions had vaginal or vulvar lesions. At least 1 of the 14 HPV genotypes was detected in females with vulvar LSIL (72.5%), vulvar HSIL (91.3%), vaginal LSIL (61.9%), and vaginal HSIL (72.7%). Considering only HPV-positive lesions, the nine most common genotypes causing cervical cancer and anogenital warts (6, 11, 16, 18, 31, 33, 45, 52, and 58) were found in 89.4% of vulvar LSILs, 100% of vulvar HSILs, 56.0% of vaginal LSILs, and 78.3% of vaginal HSILs., Conclusion: Most vulvar and vaginal lesions were attributable to at least 1 of the 14 HPV genotypes analyzed. Effective immunization programs could potentially prevent substantial numbers of HPV-related vulvar and vaginal LSILs and HSILs., Clinical Trial Registration: CLINICALTRIALS.GOV,: NCT00092521 and NCT00092534.

Background: Vulvar and vaginal cancers are considered rare cancers in women. Human Papillomavirus is responsible for 30-76% of them. The aim of this study was to describe the burden of hospital admissions by malignant neoplasia (MN) and in situ carcinoma (ISC) of vulva and vagina from 2009 to 2013, in Spain METHODS: This observational, descriptive study used discharge information obtained from the national surveillance system for hospital data, Conjunto Mínimo Básico de Datos, CMBD, provided by the Ministry of Health., Results: From 2009-2013, we found 9,896 hospitalizations coded as MN or ISC of vulva and vagina. Mean age of hospitalization was 69.94 ± 15.16 years; average length of hospital stay (ALOS) was 10.02 ± 12.40 days, and mean hospitalization costs were 5,140.31 ± 3,220.61 euros. Mean hospitalization rate was 9.874 per 100,000 women aged >14 years old (95% CI: 9.689-10.058); mean mortality rate was 0.932 per 100,000 women aged >14 years old (95% CI: 0.872-0.991) and mean case fatality rate was 9.438% (95% CI: 8.862-10.014)., Conclusion: MN and ISC of vulva and vagina are responsible for a considerable hospitalization burden. Information about these hospitalizations could be useful for cost effectiveness analysis and monitoring of HPV vaccination effectiveness., (Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: To evaluate the clinical outcomes of vaginal intraepithelial neoplasia (VAIN) and to assess the risk of recurrence and progression to invasive vaginal carcinoma., Methods: A retrospective review of the clinicopathologic data and clinical outcomes was performed on patients who were diagnosed with VAIN at a single center between January 2000 and July 2016. Demographics, treatments, and clinical outcomes were abstracted from medical records., Results: A total of 576 patients with VAIN1-3 were included in the study analysis. The distribution of VAIN1-3 was as follows: VAIN1 31.1%, VAIN2 45.3%, and VAIN3/carcinoma in situ (CIS) 23.6%. In VAIN1 patients, observation was performed in 29.1% of the cases and 48.8% obtained regression. In VAIN2+ patients, management included observation (3.5%), topical management (6.5%), laser ablation (75.3%), excision (14.1%), and radiotherapy (0.5%) with the following rates of recurrence/progression: 46.2%, 62.5%, 26.4%, 32.7%, and 0%, respectively. Four patients among VAIN3/CIS patients (3.2%) developed invasive vaginal cancer during the follow-up period with a median time to cancer diagnosis of 21.4 months (range, 5.0-44.8 months). On multivariate analysis, high-risk human papillomavirus (HPV) positivity and treatment method were found to be independent risk factors for recurrence and progression (p=0.003 and p=0.001)., Conclusion: Patients with VAIN are at high-risk of recurrence, but the risk of progression to vaginal cancer is relatively low. Laser or excision provides higher regression rate than topical agent or observation, and high-risk HPV positivity is a risk factor for recurrence. Whatever the treatment method is used, however, the high rate of recurrence warrants long-term follow-up surveillance., Competing Interests: No potential conflict of interest relevant to this article was reported., (Copyright © 2018. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology)

Our objective was to develop and test a dynamic simulation model of human papillomavirus (HPV)-related diseases to assess rational vaccination strategies in Argentina. A dynamic stochastic transmission model for hetero- and homosexual transmission of HPV oncogenic and low-risk oncogenic types among females and males was developed. The model included HPV transmission and vaccination, the natural history of HPV-related diseases, disease outcomes, and cervical cancer screening. Considering all cervical cancers, covered or not by the current quadrivalent vaccine, the existing coverage rate would lead to 60% reduction in the global incidence of cervical cancer at 25 years, and to 79% at 50 years. Isolated current female vaccination without a screening program would need around 100 years to eliminate cervical cancer from the local population. Current coverage rate would lead to 59% reduction of vulvar cancer, 76% of vaginal cancer, 85% of anal cancer, and 87% of oropharyngeal cancer, estimated over a 25-year time prospect. Female HPV vaccination within the context of current cervical cancer screening should reach a minimum long-term mean coverage of 60% of girls, receiving at least a two-dose vaccine schedule, to significantly reduce or virtually eliminate cervical cancer at 50 years. Including vaccination to boys to improve herd immunity did not influence the incidence of cervical cancer over time, as long as female coverage did not fall below 50%. Regarding vulvar, vaginal, anal, penile, and some oropharyngeal cancers, current girls-only based vaccination could virtually eliminate these cancer types after 35-40 years, both in women and men.

Background: Estonia has high cervical cancer incidence and low screening coverage. We modelled the impact of population-based bivalent, quadrivalent or nonavalent HPV vaccination alongside cervical cancer screening., Methods: A Markov cohort model of the natural history of HPV infection was used to assess the cost-effectiveness of vaccinating a cohort of 12-year-old girls with bivalent, quadrivalent or nonavalent vaccine in two doses in a national, school-based vaccination programme. The model followed the natural progression of HPV infection into subsequent genital warts (GW); premalignant lesions (CIN1-3); cervical, oropharyngeal, vulvar, vaginal and anal cancer. Vaccine coverage was assumed to be 70%. A time horizon of 88years (up to 100years of age) was used to capture all lifetime vaccination costs and benefits. Costs and utilities were discounted using an annual discount rate of 5%., Results: Vaccination of 12-year-old girls alongside screening compared to screening alone had an incremental cost-effectiveness ratio (ICER) of €14,007 (bivalent), €14,067 (quadrivalent) and €11,633 (nonavalent) per quality-adjusted life-year (QALY) in the base-case scenario and ranged between €5367-21,711, €5142-21,800 and €4563-18,142, respectively, in sensitivity analysis. The results were most sensitive to changes in discount rate, vaccination regimen, vaccine prices and cervical cancer screening coverage., Conclusion: Vaccination of 12-year-old girls alongside current cervical cancer screening can be considered a cost-effective intervention in Estonia. Adding HPV vaccination to the national immunisation schedule is expected to prevent a considerable number of HPV infections, genital warts, premalignant lesions, HPV related cancers and deaths. Although in our model ICERs varied slightly depending on the vaccine used, they generally fell within the same range. Cost-effectiveness of HPV vaccination was found to be most dependent on vaccine cost and duration of vaccine immunity, but not on the type of vaccine used., (Copyright © 2017 Elsevier Ltd. All rights reserved.)