Epidemiology of human papillomavirus-associated anogenital cancers in Granada: a three-decade population-based study.

Introduction: HPV infection is a common risk factor for all anogenital cancers. However, there are important differences in the epidemiology of anogenital cancers and these have not been compared considering diverse epidemiological indicators over a long period of time. To fill this gap, we investigated incidence, mortality, and survival trends of anogenital cancers over a period of three decades. Methods: We conducted an observational registry-based study using data from the population-based cancer registry of Granada in southern Spain. We collected data on all incident cases of anogenital cancer (cervical, anal, penile, vulvar, and vaginal cancer) diagnosed between 1985 and 2017. We calculated crude and age-standardized incidence and mortality rates, and 1, 3, and 5-year overall and net survival. We further conducted time-trend analysis calculating annual percent changes (APC) for each cancer site. Results: The incidence of anogenital cancers decreased slightly during the past 30 years, with the exception of vulvar cancer, where a slight increase was observed. Mortality decreased significantly for cervical cancer over the study period but increased non-significantly for the remaining cancer sites. Survival rates were similar to those reported in comparable countries and increased for cervical and vulvar cancer. Discussion: Cervical cancer was the greatest contributor to the burden of anogenital cancers and showed a marked improvement in all indicators in comparison to the remaining cancer sites.

Genital and extragenital oncological risk in women with vulvar lichen sclerosus: A multi-center Italian study.

Vulvar lichen sclerosus is a chronic inflammatory disease involving vulvar skin. The risk of developing invasive vulvar cancer for women with LS is reported in the literature, but the risk of extra-vulvar tumors has been under-investigated. This multicentric study aims to estimate the risk of developing cancers in a cohort of women with a diagnosis of vulvar lichen sclerosus. METHODS: A cohort of women diagnosed with and treated for vulvar lichen sclerosus in three Italian gynecological and dermatological clinics (Turin, Florence, and Ferrara) was retrospectively reviewed. Patient data were linked to cancer registries of the respective regions. The risk of subsequent cancer was estimated by dividing the number of observed and expected cases by the standardized incidence ratio. RESULTS: Among 3414 women with a diagnosis of vulvar lichen sclerosus corresponding to 38,210 person-years of follow-up (mean 11.2 years) we identified 229 cancers (excluding skin cancers and tumors present at the time of diagnosis). We found an increased risk of vulvar cancer (standardized incidence ratio = 17.4; 95 % CL 13.4-22.7), vaginal cancer (standardized incidence ratio = 2.7; 95 % CL 0.32-9.771), and oropharyngeal cancer (standardized incidence ratio = 2.5; 95 % CL 1.1-5.0), and a reduced risk of other gynecological tumors (cervical, endometrial, ovarian) and breast cancer. CONCLUSIONS: Patients with vulvar lichen sclerosus should undergo annual gynecological check-up with careful evaluation of the vulva and vagina. The increased risk of oropharyngeal cancer also suggests the need to investigate oropharyngeal cavity symptoms and lesions in patients with vulvar lichen sclerosus.

TP53 Mutation-driven Stratified Mucin-producing Carcinoma Coexisting With Squamous Cell Carcinoma of the Vulva: A Case Study.

Associated with high-risk human papillomavirus infection, invasive stratified mucin-producing carcinoma is a recently characterized adenocarcinoma of the cervix. It often occurs in association with adjacent stratified mucin-producing intraepithelial lesion. Differentiated vulvar intraepithelial neoplasia and related invasive squamous cell carcinoma often arise in background vulvar lichen sclerosus with TP53 mutation as the underlying molecular signature. We present a unique case of vulvar invasive stratified mucin-producing carcinoma-like component coexisting with invasive squamous cell carcinoma in a 64-year-old woman. Both neoplastic components were proven TP53 -driven processes arising in the background of differentiated vulvar intraepithelial neoplasia and lichen sclerosus. The invasive stratified mucin-producing carcinoma-like component behaved aggressively in this case, evidenced by the presence of lymphovascular invasion and inguinal lymph node metastasis.

The modified 5-item frailty index is a predictor of post-operative complications in vulvar cancer: a National Surgical Quality Improvement Program (NSQIP) analysis.

OBJECTIVE: To determine whether frailty is associated with post-operative complications following surgery for vulvar cancer. METHODS: This retrospective study used a multi-institutional dataset from the National Surgical Quality Improvement Program (NSQIP) database (2014-2020) to analyze the relationship between frailty, procedure type, and post-operative complications. Frailty was determined using the modified frailty index-5 (mFI-5). Univariate and multivariable-adjusted logistic regression analyses were performed. RESULTS: Of 886 women, 49.9% underwent radical vulvectomy alone, and 19.5% and 30.6% underwent concurrent unilateral or bilateral inguinofemoral lymphadenectomy, respectively; 24.5% had mFI ≥2 and were considered frail. Compared with non-frail women, those with an mFI ≥2 were more likely to have an unplanned readmission (12.9% vs 7.8%, p=0.02), wound disruption (8.3% vs 4.2%, p=0.02), and deep surgical site infection (3.7% vs 1.4%, p=0.04). On multivariable-adjusted models, frailty was a significant predictor for minor (OR 1.58, 95% CI 1.09 to 2.30) and any complications (OR 1.46, 95% CI 1.02 to 2.08). Specifically, for radical vulvectomy with bilateral inguinofemoral lymphadenectomy, frailty was significantly associated with major (OR 2.13, 95% CI 1.03 to 4.40) and any complications (OR 2.10, 95% CI 1.14 to 3.87). CONCLUSION: In this analysis of the NSQIP database, nearly 25% of women undergoing radical vulvectomy were considered frail. Frailty was associated with increased post-operative complications, especially in women concurrently undergoing bilateral inguinofemoral lymphadenectomy. Frailty screening prior to radical vulvectomy may assist in patient counseling and improve post-operative outcomes.

Characterization of patients with vulvar lichen sclerosus and association to vulvar carcinoma: a retrospective single center analysis.

PURPOSE: Lichen sclerosus (LS) is a benign, cutaneous, chronic inflammatory (autoimmunological) disease. The differentiated vulvar intraepithelial neoplasia (dVIN) accounts for a precursor lesion of vulvar squamous cell carcinoma and is often associated with lichen sclerosus. Although the association between lichen sclerosus and vulvar carcinoma has long been recognized, there is a lack of evidence in literature. METHODS: This retrospective study examined pseudonymized data of 499 women diagnosed with vulvar pathology between 2008 and 2020 at the Department of Gynaecology and Obstetrics of Hannover Medical School (MHH). Data were further stratified for the time of onset, location of disease, accompanying disease, HPV status and progression of disease into vulvar squamous cell carcinoma (VSCC). RESULTS: In total, 56 patients were diagnosed with vulvar lichen sclerosus. The mean onset of disease was at 60.3 years of age. After subdividing cases of diagnosed LS into those who did not develop vulvar carcinoma in their course and those who did, the ages at onset are 52.66 ± 17.35 and 68.41 ± 10.87, respectively. The incidence of vulvar cancer in women diagnosed with lichen sclerosus was 48.2%. Twenty-five patients reported a diagnosis of VIN in their self-reported history. CONCLUSIONS: In our retrospective study, we showed a trend between vulvar lichen sclerosus and VSCC. The difference between the two age groups of patients diagnosed with lichen sclerosus who developed vulvar carcinoma and those who did not is statistically significant. Our results highlight the importance to diagnose lichen sclerosus early to ensure adequate follow-up and prevent progression to VSCC.

An Unusual Case of Vulvar Involvement in the Course of Granulomatosis with Polyangiitis.

Granulomatosis with polyangiitis is a rare autoimmune disease with the presence of c-ANCA in most cases. It involves necrotizing inflammation in small and medium-sized vessels with multiple granulomas. The disease can affect many systems, but the typical triad of attacked systems are the upper and lower respiratory tracts and kidneys, with varying degrees of severity. Involvement of the respiratory tract may manifest, among other symptoms, as nasal crusting, nosebleeds, and dyspnea. Among patients with granulomatosis with polyangiitis, only less than 1% develop genitourinary system involvement. We present a case study of a 36-year-old woman with an 8-year-long GPA history and a lesion, which, due to its appearance and accompanying symptoms, aroused the suspicion of a neoplasm but was proven to be a granuloma with a nontypical location. The systemic disease was treated with glucocorticosteroids and cyclophosphamide. The lesion on the labium minus was surgically removed. We concluded that the macroscopic picture of GPA of the vulva and vulvar cancer is similar. The patient's medical history may help differentiate GPA and vulvar cancer. Although vulvar GPA is extremely rare, it should be considered in the differential diagnosis of vulvar lesions, especially those suspected to be oncological.

Comorbid Vulvar Lichen Sclerosus and High-Grade Squamous Intraepithelial Lesions: A Management Conundrum.

OBJECTIVE: This study aimed to determine if treating lichen sclerosus (LS) with high-potency topical corticosteroids (TCS) increases the risk of high-grade squamous intraepithelial lesion (HSIL) recurrence in patients with comorbid vulvar LS and HSIL. METHODS: This is a retrospective study of patients with comorbid vulvar LS and HSIL treated with TCS between 2015 and 2020. Patients with clinically diagnosed or biopsy-proven LS and biopsy-proven HSIL of the vulva were included. Clinical data included demographics, tobacco use, immune-modifying conditions, specimen pathology, treatment types, and HSIL recurrence. Bivariate analysis was performed to compare demographic and clinical characteristics between patients with and without HSIL recurrence. RESULTS: Twenty-six patients with comorbid LS and HSIL were identified. The median age was 66.0 years and median time in treatment for LS was 5.5 years. Thirteen (50%) had recurrence of HSIL and 13 (50%) did not have recurrence. Exposure to high-potency TCS was present in 20 (77%) patients, with 17 (65%) having use of more than 1-year duration and 9 (35%) having use at the time of HSIL diagnosis. When comparing the groups with and without HSIL recurrence, there was no significant difference in high-potency TCS exposure, duration of use, or use at time of HSIL diagnosis. CONCLUSIONS: High-potency TCS use for the treatment of LS did not seem to increase the risk of HSIL recurrence in patients with comorbid vulvar LS and HSIL. This suggests that high-potency TCS can be appropriately used for the treatment of LS even when HPV-associated disease is present.

Vulvar Cancer Incidence in the United States and its Relationship to Human Papillomavirus Vaccinations, 2001-2018.

The human papillomavirus (HPV) vaccine was indicated for the prevention of vulvovaginal cancers in 2008, but its impact on the incidence of vulvar cancers within the US is unknown. To determine this, we conducted a secondary analysis of 88,942 vulvar cancer cases among women 20+ years old using the US Cancer Statistics 2001-2018 databases. Data were stratified by tumor behavior (in situ or invasive), age (20-44, 45-64, 65+ years old), race/ethnicity (non-Hispanic White, non-Hispanic Black, Hispanic), and US census region (Northeast, South, Midwest, West), and incidence rates and average annual percentage changes (AAPC) were calculated by group. Reversing previous trends, the incidence of vulvar carcinoma in situ significantly decreased between 2001 and 2018 among women from all age groups, races/ethnicities, and regions (combined AAPC,  -4.3; 95% confidence interval (CI), -4.7 to -3.8). The incidence of invasive vulvar squamous cell carcinoma decreased significantly among 20- to 44-year-old women (AAPC, -0.8; 95% CI, -1.3 to -0.3), but significantly increased among those 45 to 64 (AAPC, 2.3; 95% CI, 1.8-2.8) and 65+ years old (AAPC, 1.2; 95% CI, 1.1-1.4). Regardless of tumor behavior, incidence was highest among non-Hispanic Whites and the Midwest region. Overall, the significant declines in vulvar carcinoma in situ among all ages, as well as invasive vulvar cancer among younger women, are encouraging and complement other recent data suggesting HPV vaccinations are already reducing anal and cervical cancer incidence. Over time, further declines in vulvar carcinoma incidence are likely as uptake and completion rates of the HPV vaccine increase in the US. PREVENTION RELEVANCE: We found evidence that HPV vaccinations likely contributed to a decrease in the incidences of vulvar carcinoma in situ and invasive vulvar carcinoma among 20- to 44-year-old women between 2001 and 2018. Our data add to the growing evidence that HPV vaccinations are reducing the incidence of HPV-related anogenital cancers.

Risk of Development of Vulvar Cancer in Women With Lichen Sclerosus or Lichen Planus: A Systematic Review.

OBJECTIVE: Vulvar lichen sclerosus (VLS) and possibly vulvar lichen planus (VLP) are associated with an increased vulvar cancer (VC) risk. We analyzed the risk of VC and its precursors after a diagnosis of VLS or VLP. MATERIALS AND METHODS: A search was performed to identify articles describing the development of vulvar neoplasia in women with VLS or VLP. This systematic review was registered with the PROSPERO database. RESULTS: Fourteen studies on VLS included 14,030 women without a history of vulvar neoplasia. Vulvar cancer, differentiated vulvar intraepithelial neoplasia (dVIN), and vulvar high-grade squamous intraepithelial lesion occurred in 2.2% (314/14,030), 1.2% (50/4,175), and 0.4% (2/460), respectively. Considering women with previous or current VC, the rate was 4.0% (580/14,372). In one study, dVIN preceded VC in 52.0% of the cases. Progression of dVIN to VC was 18.1% (2/11).The risk was significantly higher in the first 1-3 years after a biopsy of VLS and with advancing age; it significantly decreased with ultrapotent topical steroid use.For the 14,268 women with VLP (8 studies), the rates of VC, dVIN, and vulvar high-grade squamous intraepithelial lesion were 0.3% (38/14,268), 2.5% (17/689), and 1.4% (10/711), respectively. CONCLUSIONS: Vulvar lichen sclerosus is associated with an increased risk of VC, especially in the presence of dVIN and with advancing age. Ultrapotent topical steroids seem to reduce this risk. An increased risk of developing VC has been suggested for VLP. Hence, treatment and regular life-long follow-up should be offered to women with VLS or VLP.

Complications and risk factors in vulvar cancer surgery - A population-based study.

INTRODUCTION: Primary surgery for vulvar cancer has become less radical in past decades. This study investigates risk factors and prevalence of short-and long-term complications after up-to-date vulvar cancer surgery. METHODS: Population-based cohort study of surgically treated primary vulvar cancer at a national center of vulvar cancer, assessing surgical outcome. The Swedish Quality Registry for Gynecological Cancer was used for identification, journals reviewed and surgical outcome including complications within 30 days and one year registered. Multivariable logistic regression analysis comprising risk factors of short-term complications; age>80 years, BMI, smoking, diabetes, lichen sclerosus and FIGO stage was performed. RESULTS: 182 patients were identified, whereas 55 had vulvar surgery only, 53 surgery including sentinel lymph node biopsy (SLNB) and 72 surgery including inguinofemoral lymphadenectomy (IFL), with short-term complication rates of 21.8%, 39.6% and 54.2% respectively. Vulvar wound dehiscence was reported in 6.0% and infection in 13.7%. Complication rates were lower after SLNB than IFL (wound dehiscence 0% vs 8.3%; p = 0.04, infection 15.1% vs 36.1%; p = 0.01 and lymphocele 5.7% vs 9.7%; p = 0.52). Severe complications were rare. Persisting lymphedema evolved in 3.8% after SLNB and in 38.6% after IFL (p = 0.001), ubiquitous after adjuvant radiotherapy. In multivariable regression analysis, no associations between included risk factors and complications were found. CONCLUSION: Surgical complications are still common in vulvar cancer surgery and increase with the extent of groin surgery. To thrive for early diagnosis and to avoid IFL seem to be the most important factors in minimizing short-and long-term complications.

Clinical impact of SARS-CoV-2 infection among patients with vulvar cancer: the Gemelli Vul.Can multidisciplinary team.

BACKGROUND: 'Severe acute respiratory syndrome coronavirus-2' (SARS-CoV-2) infection has dramatically affected the management of patients with cancer, who are most vulnerable to the consequences of the infection. Patients with vulvar cancer are frequently elderly and affected by multiple co-morbidities, thus representing a particularly frail population. OBJECTIVE: To assess the clinical impact of the SARS-CoV-2 infection among patients scheduled for treatment for active vulvar cancer. METHODS: Data on patients with vulvar tumors referred to Fondazione Policlinico Universitario Agostino Gemelli IRCCS between February 2020 and July 2021 were retrospectively analyzed. Patients with a positive reverse transcription polymerase chain reaction in nasopharyngeal swab were considered as positive for SARS-Cov-2. RESULTS: One hundred and ninety-one patients with vulvar cancer were evaluated and scheduled for treatment. The median age was 72 years (range 35-94). Seven (3.7%) patients were diagnosed with SARS-Cov-2 infection: three (42.9%) had their treatment delayed, with no apparent consequences, two (28.6%) had their treatment delayed and later abandoned because of clinical worsening due to oncologic disease progression, and two (28.6%) contracted the infection in the post-operative period and died due to respiratory complications. CONCLUSIONS: In most cases the infection had major clinical implications, being associated with significant delays in oncologic treatments and extremely high mortality when contracted in the post-operative period.

Acantholytic Squamous Cell Carcinoma Arising From Lichen Sclerosus: A Rare Case Affecting Vulvar Skin.

We present the case of an 82-year-old female with acantholytic squamous cell carcinoma affecting vulvar skin. The patient had a history of perineal lichen sclerosus for 5 years before presentation. She was referred to a dermatologist for intractable severe pain associated with the lesions. Biopsies showed an infiltrative squamous cell carcinoma with histology consistent with the acantholytic subtype. Acantholytic squamous cell carcinoma is a rare histologic variant characterized by dyscohesive keratinocytes with pseudoglandular formation and dyskeratosis. It is associated with sun-damaged skin and most commonly occurs in the head and neck of elderly men. Few cases have been reported at nondermal sites and non-sun-exposed dermis. The patient underwent a radical vulvectomy and bilateral inguinal node dissection. The 1.6 cm tumor was diffusely acantholytic and pseudoglands were present. The tumor cells were diffusely positive for p63 immunohistochemical stain. As expected at this site, there was no solar elastosis identified histologically. However, vulvar intraepithelial neoplasia and chronic lichen sclerosus were apparent. This case represents a rare histologic subtype of squamous cell carcinoma in an unusual site associated with lichen sclerosus instead of solar elastosis.

Giant fibroepithelial vulvar polyp in a pregnant woman.

Fibroepithelial polyps are benign lesions that may appear in the vulvovaginal region. They usually occur in women of reproductive age and tend to grow up to 5 cm, but there are some rare cases in which they grow up to 20 cm. We report a case of a 22-year-old woman in the third trimester of her first pregnancy with spontaneous bleeding from a pedunculated mass measuring 15 cm in the widest diameter on the right side of the vulva. Features of this case are discussed as well as its implications, especially regarding the decision of labour. Due to the big size of the mass and its propensity to bleed, we decided to perform an elective caesarean section as well as its excision.

18F-FDG PET/CT imaging of vulva cancer recurrence: A comparison of PET-derived metabolic parameters between women with and without HIV infection.

OBJECTIVE: To assess the patterns of recurrence of vulva cancer on 18F-FDG PET/CT and to compare the 18F-FDG PET metabolic metrics in patients with and without Human Immunodeficiency Virus (HIV). METHODS: Maximum standardized uptake value (SUVmax), mean standardized uptake value (SUVmean), metabolic tumour volume (MTV and total lesion glycolysis (TLG) were obtained on Flourine-18 Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography (18F-FDG PET/CT) images of women referred with suspected or confirmed vulva cancer recurrence. We compared HIV-infected and HIV-uninfected patients regarding pattern disease recurrence, age at diagnosis, and the PET-derived metabolic indices. RESULTS: We analyzed 33 patients with a mean age 50.76 ± 15.78 including 21 HIV-infected women. The majority of patients (94 %) had squamous cell carcinoma and 84.85 % were Blacks. Of the HIV-infected individuals, the median CD4 count was 526.0 cells/mm3 (IQR: 379.0-729.0). HIV infected patients were younger than the HIV uninfected at the time of diagnosis: 40.50 ±â€Š8.87 vs 66.54 ±â€Š9.71 respectively, p < 0.001. We found a local (vulvar) recurrence rate of 75.8 %. Nodal pelvic recurrences were higher in the HIV-infected patients than in the HIV uninfected patients (70 % vs 30 %, p = 0.027). Three patients had distant metastasis and all three were HIV-infected. There was a higher whole-body MTV and TLG among HIV-infected women compared with HIV-uninfected women, 103.39 vs 17.58 and 852.64 vs 101.79, respectively (p < 0.05 for both). CONCLUSION: HIV-infected women are diagnosed with vulva cancer at a younger age. HIV-infected patients had a higher rate of pelvic lymph node recurrence. There is a higher tumor burden at vulva cancer recurrence among women with HIV infection.