Complications of obliterative versus reconstructive vaginal surgery for pelvic organ prolapse in octogenarians: A retrospective cohort study.

AIMS: Women of advanced age may choose between restorative or obliterative surgery for surgical management of pelvic organ prolapse. Obliterative surgery is traditionally reserved for a subset of older women with more severe medical comorbidities, since obliterative approaches are generally considered to be less morbid and older individuals have higher rates of perioperative complications than younger cohorts. This study compared perioperative complications amongst octogenarians undergoing obliterative versus reconstructive approaches. This data will help to inform perioperative counselling as previous studies have not been powered to evaluate complications in this population. METHODS: The National Surgical Quality Improvement Program database was used to identify patients that had Pelvic organ prolapse surgery between 2012 and 2021, aged 80 years or older. Single-compartment procedures, vaginal mesh procedures, and oncologic surgery were excluded. The primary outcome was any complication within the first 30 days excluding urinary tract infection (UTI). UTI, readmission, and severe complications were secondary outcomes. RESULTS: Of the 4149 patients identified, 2514 (60.6%) underwent reconstructive surgery and 1635 (39.4%) underwent obliterative surgery. Patients undergoing reconstructive surgery were more likely to have an American Society of Anesthesiologists (ASA) class of 1 or 2 (46.1% vs. 31.3%, p = 0.002) and were less likely to be on antihypertensive medication (72.0% vs. 75.8%, p = 0.006). Further, there was an increased length of stay (1.47 ± 1.84 vs. 1.03 ± 1.31 days, p < 0.001) in hospital for reconstructive surgery which was more often performed as an inpatient (45.7% vs. 37.9%, p < 0.001). There was no difference in the primary outcome: any complication excluding UTIs. However, UTI was more common in the reconstructive group (aOR 0.48; 95% confidence interval 0.34-0.0). The rate of serious complications (Clavien-Dindo Class IV) was low overall and not different between reconstructive and obliterative approaches (1.3% vs. 1.0%, respectively). CONCLUSIONS: Both vaginal reconstructive and obliterative approaches have low complication rates in octogenarians, with only UTI rate being different between cohorts. When choosing surgical approach, we suggest a case-based, patient center discussion on the anatomic outcomes, durability and patient satisfaction.

Effectiveness of prophylactic pharmacological hemostatic agents for reduction of blood loss at vaginal surgery: a systematic review and meta-analysis.

INTRODUCTION AND HYPOTHESIS: The objective was to evaluate the effectiveness of pharmacological hemostatic agents in the reduction of blood loss at vaginal surgery. METHODS: A systematic review of randomized control trials (RCTs) was completed. We searched PubMed (1946-2022), Embase, and CINAHL, using search terms related to vaginal hysterectomies and reconstructive surgeries combined with peri-operative use of hemostatic agents. RCTs comparing hemostatic interventions with placebo or with standard care were analyzed with the primary outcome of estimated blood loss. Secondary outcomes included peri-operative complications, length of stay, blood transfusion, and readmission. Risk of bias was assessed using the Risk of Bias 2 tool. RESULTS: Nine RCTs were included with a total of 903 participants. All trials were considered to have an overall low risk of bias. Meta-analysis of six RCTs (491 participants) favored the use of vasoconstrictive agent (vasopressin/ornipressin) at the surgical site for an overall effect estimate of decreased blood loss by 70 ml (95% CI -125, -14 ml). There was significant heterogeneity of studies with both dose and technique of vasoconstrictive agents used. Only one RCT evaluated tranexamic acid and found a benefit in the prophylactic use of intravenous tranexamic acid. CONCLUSIONS: Peri-operative use of vasoconstrictive agents slightly reduces bleeding in women undergoing elective vaginal surgery. Additional studies evaluating alternative pharmacological agents such as tranexamic acid may be of benefit.

Prevalence and risk factors for urinary incontinence up to 2 years postpartum: a cross-sectional population-based study.

INTRODUCTION AND HYPOTHESIS: Urinary incontinence (UI) is common in the postpartum period; however, most studies focus on the early postpartum period and assess prevalence at only one or two time points. We hypothesized that UI would be prevalent across the first 2 years postpartum. Our secondary objective was to evaluate risk factors for postpartum UI among a nationally representative, contemporary sample. METHODS: This cross-sectional, population-based study used National Health and Nutrition Examination Survey (2011-2018) data for parous women within 24 months following delivery. Prevalence of UI, UI subtypes, and severity were estimated. Multivariate logistic regression was used to estimate adjusted odds (aOR) of UI for exposures of interest. RESULTS: Among 560 postpartum women, prevalence of any UI was 43.5%. Stress UI was most common (28.7%), and most women (82.8%) experienced mild symptoms. There was no significant change in prevalence of UI across the 24 months following delivery (R2 = 0.004). Individuals with postpartum UI tended to be older (30.3 ± 0.5 versus 28.8 ± 0.5 years) and had higher BMI (31.1 ± 0.6 versus 28.9 ± 0.6). In multivariate analysis, odds of postpartum UI were higher for women who had had a prior vaginal delivery (aOR 2.0, 95% CI: 1.3-3.3), prior delivery of a baby weighing 9 lb (4 kg) or more (aOR 2.5, 95% CI: 1.3-4.8), or who reported current smoking (aOR 1.5, 95% CI: 1.0-2.3). CONCLUSIONS: During the first 2 years postpartum 43.5% of women report UI, with relatively stable prevalence over this period. This high prevalence supports screening for UI after delivery regardless of risk factors.

Prevalence and Risk Factors for Urinary Incontinence in Nulliparous Women: A Contemporary, Population-Based Cohort Study.

IMPORTANCE AND OBJECTIVES: Epidemiologic studies of incontinence largely focus on parous women, and there are limited data regarding nulliparous women. Our objectives were to evaluate risk factors for urinary incontinence among a nationally representative, contemporary sample of nulliparous women of all ages in the United States and to describe the prevalence and subtypes of urinary incontinence and nocturia in this population. STUDY DESIGN: This cross-sectional, population-based study used the National Health and Nutrition Examination Survey cycles 2011-2018 to assemble a sample of nulliparous women 20-80 years old. Crude and adjusted odds ratios were estimated using multivariable logistic regression for the exposures of interest: body mass index (BMI), age, physical activity, prior hysterectomy, and current smoking. Prevalence of urinary incontinence and nocturia were estimated. RESULTS: Among 1,603 nulliparous women, prevalence of any urinary incontinence was 29.38%. Prevalence of stress, urgency, and mixed urinary incontinence and nocturia, respectively, were 27.68%, 19.64%, 10.57%, and 58.95%. Women with a BMI ≥25 (calculated as weight in kilograms divided by height in meters squared; adjusted odds ratio [aOR], 1.57; 95% confidence interval [CI], 1.11-2.23), at least 45 years (aOR, 3.75; 95% CI, 2.31-5.83), and current smoking (aOR, 1.63; 95% CI, 1.07-2.49) had increased the odds of incontinence compared with women without these risk factors. When stress urinary incontinence (SUI) was considered alone, only women with a BMI ≥25 (aOR, 1.66; 95% CI, 1.20-2.31) and age at least 45 years (aOR, 3.17; 95% CI, 2.01-5.00) had increased odds of SUI compared with women without these risk factors. CONCLUSIONS: Urinary incontinence and nocturia are prevalent in nulliparous women, and age, elevated BMI, and current smoking may represent risk factors for incontinence in this population.

Complications Following Posterior Colporrhaphy With and Without Anal Sphincteroplasty: An Analysis of Cases in the National Surgical Quality Improvement Program Database.

OBJECTIVE: We aimed to compare postoperative complications for patients undergoing posterior colporrhaphy with or without sphincteroplasty. METHODS: A retrospective cohort of women undergoing posterior colporrhaphy with or without anal sphincteroplasty was completed using the National Surgery Quality Improvement Program (NSQIP) database (2012-2019). The primary outcome was a composite of important surgical complications, including wound complications, blood transfusion, hospital stay >48 hours, reoperation, readmission, and urinary tract infection. Multivariable logistic regression was used to adjust for important potential confounders, including age, BMI, diabetes, and anterior prolapse surgery. RESULTS: A total of 5079 patients were included. Of these, 82 patients underwent a concurrent sphincteroplasty. The primary composite outcome occurred in 10.4% of patients having posterior colporrhaphy versus 19.5% having posterior colporrhaphy with sphincteroplasty. On multivariable analysis there was no increased odds of complication associated with concomitant anal sphincteroplasty (1.58, 95% CI 0.89-2.90, P = 0.12). CONCLUSION: Nearly one in five women who have posterior colporrhaphy with anal sphincteroplasty had an important surgical complication. Higher complication rates may be related to patient factors, as this was not observed after adjustment for patient factors and additional surgical procedures. Sphincteroplasty may be considered with posterior colporrhaphy in select women.

Complications After Uterosacral Ligament Suspension Versus Sacrospinous Ligament Fixation at Vaginal Hysterectomy: A Retrospective Cohort Study of the National Surgical Quality Improvement Program Database.

IMPORTANCE: Apical suspension, including uterosacral ligament suspension (USLS) and sacrospinous ligament fixation (SSLF), is the standard of care at vaginal hysterectomy. Although the equivalence of anatomic and clinical outcomes after USLS and SSLF is established, comparing surgical complications specific to patients undergoing concurrent vaginal hysterectomy further informs decision making regarding operative approach. OBJECTIVE: This study aims to compare complications in the first 30 days after surgery in patients undergoing USLS and SSLF at vaginal hysterectomy for pelvic organ prolapse. STUDY DESIGN: This retrospective, population-based cohort study used the American College of Surgeons National Surgical Quality Improvement Program database to identify patients undergoing USLS or SSLF at vaginal hysterectomy for pelvic organ prolapse between 2012 and 2019. The primary outcome was a composite of surgical complications excluding urinary tract infection (UTI). Odds of the primary outcome, readmission, reoperation, and UTI were evaluated by multivariable logistic regression models. RESULTS: Of 10,210 eligible patients, 7,127 patients underwent USLS and 3,083 patients underwent SSLF. Uterosacral ligament suspension was associated with a 25% lower odds of the composite complication outcome that excluded UTI compared with SSLF (adjusted odds ratio, 0.75; 95% confidence interval, 0.63-0.90). Urinary tract infection was the most common complication and occurred more commonly in patients undergoing USLS (6.5% vs 4.9%; adjusted odds ratio, 1.29; 95% confidence interval, 1.06-1.56). There was no significant difference in Clavien-Dindo class IV complications, readmission, or reoperation between approaches. CONCLUSION: Uterosacral ligament suspension was associated with a lower odds of complications excluding UTI compared with SSLF. Urinary tract infection was more common among patients having USLS. The odds of serious complications, readmission, and reoperation were low and comparable between groups.

Complications After Vaginal Vault Suspension Versus Minimally Invasive Sacrocolpopexy in Women With Elevated Body Mass Index: A Retrospective Cohort Study Using Data From the National Surgical Quality Improvement Program Database.

IMPORTANCE: Overweight and obese women represent a growing share of pelvic floor reconstruction surgeons' practices. Determining perioperative risk specific to this population is essential to inform decision making regarding operative approach in this population. OBJECTIVE: The aim of the study was to compare surgical complications among overweight and obese women undergoing apical compartment prolapse surgery by either minimally invasive abdominal or vaginal approach. STUDY DESIGN: The American College of Surgeons National Surgical Quality Improvement Database was used to identify overweight and obese patients (body mass index ≥ 25) undergoing either minimally invasive sacrocolpopexy (MISC) or vaginal vault suspension (VVS) in the form of a sacrospinous vault fixation or uterosacral ligament fixation for pelvic organ prolapse from 2012 to 2019. Odds ratios for surgical complications, readmission, and reoperation were estimated using multivariable logistic regression. RESULTS: Of 8,990 eligible patients, 5,851 underwent a VVS and 3,139 patients underwent MISC. There was a greater odds of any complication in the first 30 days following VVS (n = 608 [10.4%]) compared with MISC (n = 247 [7.9%]; odds ratio, 1.27; 95% confidence interval, 1.08-1.48) on multivariable analysis. Urinary tract infections (UTIs) were the most common complication and were more likely following VVS (112 (3.6%) versus 350 (6.0%), P < 0.001). When UTIs were excluded, there was no difference in complications between approaches (1.00; 95% CI, 0.82-1.22). There were no statistically significant odds of readmission, reoperation, or serious complications between approaches. CONCLUSIONS: Vaginal vault suspension may be associated with a higher odds of any complication compared with MISC in overweight and obese women, but the rate of serious complications, readmission, and reoperation are low, and approaches were comparable when considering complications other than UTI.

Risk Factors for Urologic Injury in Women Undergoing Hysterectomy for Benign Indication.

OBJECTIVE: To investigate risk factors associated with urologic injury in women undergoing hysterectomy for benign indication. METHODS: A retrospective cohort study for the period of 2011-2018 was conducted using the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) database. Women without urologic injury were compared with women with injury. A pre-specified multivariable logistic regression model, controlling for key patient demographic factors and intraoperative variables, was used to assess for surgical factors associated with urologic injury. RESULTS: Among 262 117 women who underwent hysterectomy for benign indication, 1539 (0.6%) sustained urologic injury. On average, patients with urologic injury were younger, had lower body mass index (BMI), and more frequently underwent a transabdominal surgical approach. Patients who underwent total hysterectomy had increased odds of urologic injury than those who underwent subtotal hysterectomy (adjusted OR [aOR] 1.49; 95% confidence interval [CI] 1.21-1.84). Patients with class III obesity had lower odds of injury than patients with normal BMI (aOR 0.64; 95% CI 0.51-0.80). For risk of urologic injury, an interaction was observed between surgical approach and surgical indication. Abdominal compared with laparoscopic approach was associated with urologic injury for women with endometriosis (aOR 2.98; 95% CI 1.99-4.47), pelvic pain (aOR 3.51; 95% CI 1.74-7.08), menstrual disorders (aOR 4.33; 95% CI 1.68-11.1), and fibroids (aOR 2.28; 95% CI 1.72-3.03). Vaginal compared with laparoscopic approach was associated with increased odds of injury for women with menstrual disorders (aOR 7.62; 95% CI 1.37-42.5). CONCLUSION: While the risk of urologic injury during hysterectomy for benign indication is low, the risk is dependent on patient disease factors and surgical approach.

Short term complications in mesh augmented vaginal repair of pelvic organ prolapse are not higher when compared with native tissue repair.

INTRODUCTION AND HYPOTHESIS: Accumulating evidence regarding the negative long-term consequences of transvaginal mesh-based procedures for pelvic organ prolapse has led to a sharp decline in mesh-based procedures. We aimed to evaluate the short-term complications of mesh-based procedures for carefully selected patients with pelvic organ prolapse after Food and Drug Administration warnings. METHODS: A retrospective database review of the ACS NSQIP database was completed to examine 30-day complications including re-operation, prolonged length of stay, blood transfusion, surgical site infection, urinary tract infection, readmission and wound dehiscence in mesh-augmented and native tissue-based transvaginal procedures for pelvic organ prolapse. RESULTS: A total of 36,234 patients were included in the analysis, with only 7.1% (2574 women) having mesh-augmented repair. Using a multivariable logistical regression analysis adjusting for confounders, we found that the primary composite outcome (re-operation, hospital stay, blood transfusion and surgical site infection) was less common in the mesh group compared with the native tissue repair group (adjusted OR 0.80, CI 0.67-0.95, p = 0.009). The secondary outcomes (urinary tract infection, re-admission and wound dehiscence) were not different between the group. CONCLUSION: These results suggest that in well-chosen patients, short-term complications are not increased when using transvaginal mesh for pelvic organ prolapse repair.

Preoperative anemia and complications after surgery for pelvic organ prolapse: an analysis of the national surgical quality improvement program database.

INTRODUCTION AND HYPOTHESIS: Preoperative anemia is a well-established risk factor for adverse perioperative outcomes in major surgery, but studies exploring complications after pelvic reconstructive surgery are limited. The objective of this study is to examine the impact of preoperative anemia on 30-day adverse outcomes in patients undergoing pelvic organ prolapse surgery. METHODS: A retrospective cohort of women undergoing pelvic organ prolapse surgery was captured from the National Surgery Quality Improvement Program database (2014-2019). The primary outcome was a composite of postoperative medical complications such as pulmonary embolism, acute renal failure, stroke, myocardial infarction, cardiac arrest, deep vein thrombosis, and sepsis. Secondary outcomes included surgical site infection, bleeding requiring blood transfusion, readmission within 7 days of surgery, and return to the operating room within 30 days. Multivariate logistic regression was used to adjust for important pre-specified potential confounders. RESULTS: A total of 50,848 women were included in the analysis and 9.9% (4,579) met the criteria for anemia (hematocrit <36%). Potentially serious medical complications were rare, occurring in only 348 women (0.7%), and were more common among anemic patients (1.1% vs 0.6%, p < 0.001). On multivariate analysis, preoperative anemia was associated with higher odds of both potentially serious medical complications (OR 1.38, 95% CI 1.01-1.88) and returning to the operating room (OR 1.55, 95% CI 1.23-1.94). Anemic patients had a four-fold increase in the odds of requiring a blood transfusion (OR 4.47, 95% CI 3.60-5.56). CONCLUSIONS: Preoperative anemia is associated with an increased risk of adverse postoperative outcomes in women having surgery for pelvic organ prolapse.

Outcomes of an Overnight-Stay Unit for Urogynecologic Surgery: Feasibility and Risk Factors for Failure of Next-Day Discharge.

OBJECTIVE: To evaluate outcomes of patients undergoing urogynecologic procedures with postoperative care in an overnight-stay unit at a tertiary care center. METHODS: A retrospective cohort study of 1644 women admitted to an overnight-stay unit at a Canadian tertiary care center after urogynecologic surgery between 2014 and 2018 was completed. A multivariable logistic regression model was fit to identify risk factors for failed next-day discharge, defined as a delayed discharge of more than 24 hours, readmission within 30 days of surgery, or emergency room assessment within 7 days of surgery. RESULTS: One thousand five hundred seventy-eight patients (96%) were discharged within 24 hours of surgery. Mean patient age was 53.7 ± 15.1 years, with 21.2% 70 years or older. Surgical approaches included laparotomies (8.9%), major vaginal surgery (70.9%), and open retropubic procedures (2.1%). Hysterectomies were performed in 1120 patients (68.1%). One hundred one patients (6.1%) were assessed in the emergency department within 7 days of surgery, and 57 (3.5%) were readmitted to hospital within 30 days of their procedure. Multivariable regression identified the following as risk factors for failed next-day discharge: pulmonary disease (odds ratio [OR], 3.26; 95% confidence interval [CI], 1.32-8.06; P = 0.010), longer operating time (OR, 1.40; 95% CI, 1.10-1.79; P = 0.006, per 60 minutes), and intraoperative hemorrhagic complications (OR, 22.64; 95% CI, 5.83-88.00, P < 0.001). CONCLUSIONS: Admission to an overnight-stay unit with next-day discharge is feasible for most patients undergoing urogynecologic surgery. Factors associated with requiring a longer hospital stay, presentation to an emergency department, or readmission to hospital within 7 days include pulmonary disease, longer operating times, and intraoperative hemorrhagic complications.

Surgical approach and unplanned readmission following pelvic organ prolapse surgery: a retrospective cohort study using data from the National Surgical Quality Improvement Program Database (NSQIP).

INTRODUCTION AND HYPOTHESIS: To define the reasons for hospital readmissions following surgery for pelvic organ prolapse by surgical approach. METHODS: Patients undergoing surgery for pelvic organ prolapse from 2012 to 2018 were identified in the American College of Surgeons National Surgical Quality Improvement Program database using Current Procedural Terminology and International Classification of Diseases codes. Hazard risks of readmission by surgical approach (vaginal, laparoscopic, abdominal, or combined) were determined by multivariable cox regression. Diagnoses and timing of readmission by surgical approach were examined. RESULTS: Of 57,233 women undergoing surgery for pelvic organ prolapse during the study period, 1073 (1.9%) were readmitted to the hospital within 30 days postoperatively. After adjusting for prespecified potential confounders, laparoscopic and abdominal surgical approaches were associated with higher risks of readmission relative to a vaginal approach (aHR 1.30, 95% CI 1.08-1.57, and 1.97, 95% CI 1.44-2.71, respectively). The most common reason for readmission was a gastrointestinal issue among those undergoing both laparoscopic (28.0%) and abdominal surgery (30.2%). Surgical site infection was the most common readmission diagnosis among women undergoing vaginal surgery (16.2%). Of the 418 women readmitted within 7 days of surgery, the most common diagnoses were gastrointestinal issues (26.6%), medical disorders (12.0%), or surgical complications (e.g., bleeding) (11.0%). CONCLUSIONS: Women undergoing laparoscopic or abdominal surgery for pelvic organ prolapse were at higher risk of readmission relative to those undergoing surgery via a vaginal approach. The reasons and timing of readmission differed based on surgical approach.

Patient attitudes toward pooled surgical waitlists in urogynecology.

INTRODUCTION AND HYPOTHESIS: Pooled surgical waitlists are used to maximize the use of surgical resources; however, patients' views of this strategy are poorly understood. We sought to evaluate patients' attitudes toward a pooled waitlist for urogynecology and pelvic reconstructive surgical procedures. METHODS: Patient and provider focus groups were used to inform the design of a survey that was distributed to patients at the time of consent for female pelvic reconstructive surgical procedures. All responses were collected anonymously. Patient attitudes toward surgical wait times and the potential for a pooled surgical waitlist were explored. Grouped responses by age, procedure type, and perceived disease severity were examined. RESULTS: One hundred seventy-six patients were surveyed. Thirty-four percent were amenable to the option of a pooled surgical waitlist; 86% agreed or strongly agreed that they preferred to have their surgery performed by their own care provider. Only 18% would agree to be on a pooled surgical waitlist if it shortened their wait time. Older women (≥ 65 years) were more likely to disagree or strongly disagree that they "would like the option of having surgery done by the next available skilled surgeon" (56.2% vs. 72.0%, p = 0.028). Self-perceived severe disease and mid-urethral sling surgery were not associated with a higher acceptance of pooled surgical waitlists. CONCLUSIONS: Acceptance of pooled surgical waitlists among urogynecology patients was overall low, irrespective of disease severity. Improving our understanding of urogynecology patients' concerns and potentially negative perceptions of surgical waitlists is needed to ensure patient comfort and satisfaction are not compromised if this strategy is adopted.

Complications after minimally invasive sacrocolpopexy with and without concomitant incontinence surgery: A National Surgical Quality Improvement Program (NSQIP) database study.

AIMS: To compare surgical complications for patients having minimally invasive sacrocolpopexy (MISCP) with concomitant incontinence procedure, to those having MISCP alone. METHODS: Patients undergoing MISCP with and without a concomitant incontinence procedure between 2006 and 2015 were identified in the American College of Surgeons National Surgical Quality Improvement Program database using Current Procedural Terminology codes. The main outcome of interest was a composite of surgical site infection, bleeding requiring blood transfusion, return to the operating room within 30 days, and surgical stay >48 h. Log-binomial regression was used to identify independent risk factors for the outcome and to generate adjusted effect measures for variables of interest. RESULTS: Seven thousand ninety-seven women met the inclusion criteria, of which 2433 (34%) underwent a concomitant incontinence procedure. Patients having incontinence procedures were slightly older (59 ± 11 vs 58 ± 12, P < 0.0001) and had longer total operating time (225 IQR 170-267 vs 184 IQR 120-232 min, P < 0.0001). Pre-operative steroid use, wound class III/IV (vs I/II), and longer operative time were independent predictors of the composite outcome. After adjusting for baseline patient characteristics and co-morbidities, no association was observed between concomitant incontinence procedure and the composite outcome (adjusted RR 0.87, 95%CI 0.65-1.18) but there was an increased likelihood of urinary tract infection (adjusted RR 2.47 95%CI 1.89-3.27). CONCLUSIONS: Despite being associated with a longer operative time, performing an incontinence procedure at the time of MSCIP was not associated with an increased risk of clinically important surgical complications other than urinary tract infection.

Vulvar Squamous Cell Carcinoma (VSCC) as Two Diseases: HPV Status Identifies Distinct Mutational Profiles Including Oncogenic Fibroblast Growth Factor Receptor 3.

Purpose: Patients with advanced or recurrent invasive vulvar squamous cell carcinoma (VSCC) have limited treatment options and a grave prognosis. Understanding the genomic landscape may facilitate the identification of new therapies and improve clinical outcomes.Experimental Design: A retrospective chart review and molecular analysis of patients with VSCC from 2000 to 2016 was performed at the Ottawa Hospital Research Institute. The presence of oncogenic human papillomavirus (HPV) was determined by nested PCR and amplified DNA was sequenced using the Ion AmpliSeq Cancer Hotspot v2 Panel. The patients were divided into two groups according to HPV status (HPV-positive versus HPV-negative) and clinical outcome correlated with mutation status using descriptive statistics.Results: In 43 VSCC patients, there was a high mutation rate in both HPV-positive (73%) and HPV-negative (90%) disease with the two subgroups expressing distinct genetic profiles. HPV-positive tumors were characterized by oncogenic mutations in PIK3CA (27%), FGFR3 (14%), and PTEN (9%), whereas HPV-negative tumors were found to have mutations in TP53 (57%), HRAS (24%), PI3KCA (19%), and CDKN2A (14%). Mutation S249C in FGFR3 occurred in 14% of HPV-positive tumors. While there were notable differences in the occurrence of TP53, HRAS, PTEN, and FGFR3 mutations according to HPV status, only the rate of TP53 mutations was statistically significant (P = 0.0004). No significant difference in prognosis was found between patients with HPV-positive and HPV-negative VSCC.Conclusions: HPV-positive VSCC is characterized by oncogenic FGFR3 mutations that helps classify this subtype as a separate disease. Inhibitors of FGFR3 merit consideration as a therapeutic strategy in this neglected cancer in women. Clin Cancer Res; 23(15); 4501-10. ©2017 AACR.