Opportunistic Salpingectomy Between 2017 and 2020: A Descriptive Analysis.

OBJECTIVES: Opportunistic salpingectomy (OS) is the removal of fallopian tubes during another pelvic surgery for the purpose of ovarian cancer prevention. Herein, we describe the rates of OS at the time of hysterectomy and tubal sterilization between 2017 and 2020. METHODS: This study uses the Canadian Institute of Health Information's Discharge Abstract Database and National Ambulatory Care Reporting System for all Canadian provinces and territories except for Quebec between the fiscal years 2017 and 2020. A descriptive analysis on all people aged 15 years and older who had hysterectomies or tubal sterilizations was conducted to determine the proportion of hysterectomies that included bilateral salpingectomy (OS) and the proportion of tubal sterilizations that were OS compared to tubal ligation. RESULTS: There were 174 006 people included in the study. The proportion of hysterectomies that included OS increased from 31.7% in 2017 to 39.9% by 2020. With respect to tubal sterilizations, rates of OS increased from 26.3% of all tubal sterilizations in 2017 to 42.5% in 2020. British Columbia remained the jurisdiction with the highest rates of OS, but rates increased significantly in many jurisdictions, particularly at the time of tubal sterilization. CONCLUSION: The rates of OS have continued to increase in all Canadian jurisdictions following the official Society of Obstetricians and Gynaecologists of Canada recommendation to consider OS in 2015. Assuming that all tubal ligations could have been OS and 75% of hysterectomies with ovarian conservation could have included OS, our data indicate 76 932 missed opportunities for ovarian cancer prevention.

Declining rates of cervical intraepithelial neoplasia in British Columbia, Canada: An ecological analysis on the effects of the school-based human papillomavirus vaccination program.

Since 2008, girls in British Columbia (BC), Canada, have been offered HPV vaccination through a school-based, publicly funded immunization program. The oldest birth cohort eligible for the vaccination program was born in 1994 and uptake is on average 63%. To evaluate the impact of the HPV vaccine in BC, ecological trends in cervical intraepithelial neoplasia (CIN) rates were assessed in young women before and after the implementation of the HPV vaccination program. Information on all Pap smears and histopathological abnormalities, in calendar years 2004-2017 in women 16-28 years of age in BC were obtained from the population-based BC Cancer Cervix Screening Program database. Rates of CIN 2 and 3 were calculated as the number of cases divided by the number of cytology specimens for that period. Rate ratios (RR) were calculated by negative binomial piecewise regression. Age-centered incidence rates of CIN 2 and 3 in BC declined significantly among women 16-23 years of age after HPV vaccine introduction compared to before vaccine introduction. The overall reduction postvaccination for CIN2 and 3 in women 16-23 years was respectively 62% (95% CI 54-68%) and 65% (95% CI 58-71%). Age-specific rates for CIN2 significantly declined for those 18-22 years of age and for those 19, 20 and 23 years of age for CIN3. Among women 24-28 years of age no decline in CIN2 and 3 rate over time was observed. The observed reduction in CIN 2 and 3 rates since the introduction of the school-based HPV vaccine program might illustrate the population impact of the BC provincial school-based HPV vaccination program.

Examining indicators of early menopause following opportunistic salpingectomy: a cohort study from British Columbia, Canada.

BACKGROUND: The fallopian tube may often be the site of origin for the most common and lethal form of ovarian cancer, high-grade serous ovarian cancer. As a result, many colleges of obstetrics and gynecology, which include the American College of Obstetricians and Gynecologists, are recommending surgical removal of the fallopian tube (bilateral salpingectomy) at the time of other gynecologic surgeries (particularly hysterectomy and tubal sterilization) in women at general population risk for ovarian cancer, collectively referred to as opportunistic salpingectomy. Previous research has illustrated no increased risk of complications after opportunistic salpingectomy. However, most studies that have examined potential hormonal consequences of opportunistic salpingectomy have had limited follow-up time and have focused on surrogate hormonal markers. OBJECTIVE: We examine whether there are differences in physician visits for menopause and filling a prescription for hormone replacement therapy among women who undergo opportunistic salpingectomy in the population of British Columbia, Canada. STUDY DESIGN: We identified all women who were ≤50 years old in British Columbia who underwent opportunistic salpingectomy from 2008-2014. We compared women who underwent opportunistic salpingectomy at hysterectomy with women who underwent hysterectomy alone and women who underwent opportunistic salpingectomy for sterilization with women who underwent tubal ligation. We used Cox Proportional hazards models to model time to physician visits for menopause and for filling a prescription for hormone replacement therapy. We calculated adjusted hazards ratios for these outcomes and adjusted for other gynecologic conditions, surgical approach, and patient age. We performed an age-stratified analysis (<40, 40-44, 45-49 years) and conducted a sensitivity analysis that included only women with ≥5 years of follow up. RESULTS: We included 41,413 women in the study. There were 6861 women who underwent hysterectomy alone, 6500 who underwent hysterectomy with opportunistic salpingectomy, 4479 who underwent hysterectomy with bilateral salpingo-oophorectomy, 18,621 who underwent tubal ligation, and 4952 who underwent opportunistic salpingectomy for sterilization. In women who underwent opportunistic salpingectomy, there was no difference in time to the first physician visit related to menopause for both women who underwent hysterectomy with opportunistic salpingectomy (adjusted hazard ratio, 0.98; 95% confidence interval, 0.88-1.09) and women who underwent opportunistic salpingectomy for sterilization (adjusted hazard ratio, 0.92; 95% confidence interval, 0.77-1.10). There was also no difference in time to filling a prescription for hormone replacement therapy for women who underwent hysterectomy with opportunistic salpingectomy or opportunistic salpingectomy for sterilization (adjusted hazard ratio, 0.82; 95% confidence interval, 0.72-0.92; and adjusted hazard ratio, 1.00; 95% confidence interval, 0.89-1.12; respectively). In contrast, we report significantly increase hazards for time to physician visit for menopause (adjusted hazard ratio, 1.95; 95% confidence interval, 1.78, 2.13) and filling a prescription for hormone replacement therapy (adjusted hazard ratio, 3.80; 95% confidence interval, 3.45, 4.18) among women who underwent hysterectomy with bilateral salpingo-oophorectomy. There were no increased hazards for physician visits for menopause or initiation of hormone replacement therapy among women who underwent opportunistic salpingectomy in any of the age-stratified analyses, nor among women with at least 5 years of follow up. CONCLUSION: Our results reveal no indication of an earlier age of onset of menopause among the population of women who underwent hysterectomy with opportunistic salpingectomy and opportunistic salpingectomy for sterilization as measured by physician visits for menopause and initiation of hormone replacement therapy. Our findings are reassuring, given that earlier age at menopause is associated with increased mortality rates, particularly from cardiovascular disease.

Screening for Anal Cancer in Women With a History of Vulvar High-Grade Squamous Intraepithelial Lesions.

OBJECTIVES: The primary obkective was to determine the prevalence of (a) a positive anal cancer screen and (b) histological anal high-grade squamous intraepithelial lesion (HSIL) in women undergoing surveillance for previously diagnosed and treated human papillomavirus (HPV)-associated vulvar HSIL. The secondary objective was to determine the patients' acceptability of the screen. MATERIALS AND METHODS: This is a single-institution, cross-sectional pilot study. Women, aged 30 to 80 years, with a history of biopsy-proven vulvar HSIL were invited to undergo screening for anal cancer. Positive screen characterized by abnormalities in any of the following: anal high-risk HPV (HR-HPV); anal cytology; and digital anorectal examination. All women with an abnormal screen were referred for high-resolution anoscopy. All women completed a postscreen questionnaire. RESULTS: Fifty-seven patients were recruited. The median (interquartile range) age was 61.5 (51.0-68.0) years. The prevalence of a positive screen was 56.1% (95% CI = 43.3%-68.2%). Of the 32 screen-positive patients, 12 had both abnormal cytology and HR-HPV, 3 had positive HR-HPV alone, and 17 had abnormal cytology alone. Of the 29 patients with a positive screen who went on to anoscopy, the prevalence of anal HSIL was 33.3% (95% CI = 19.2%-51.2%). The prevalence of anal HSIL among all of those who had screening (N = 57) was 18.2% (95% CI = 10.2%-30.3%). The examination was well tolerated with 100% of patients, indicating that they would have the screening again. CONCLUSIONS: Women with vulvar HSIL have an increased risk of developing anal HSIL. Larger studies are needed to define optimal screening protocols as well as algorithms for management in high-risk populations.

A population-based analysis of germline BRCA1 and BRCA2 testing among ovarian cancer patients in an era of histotype-specific approaches to ovarian cancer prevention.

BACKGROUND: Identifying female carriers of BRCA1 and BRCA2 mutations is imperative for prevention of ovarian cancer and breast cancer. There are five major histologic subtypes of ovarian cancer and high grade serous cancer (the most common) is reported in 75-100% of BRCA1 and BRCA2 mutation carriers. We examined histology-based referral to the Hereditary Cancer Program following an educational prevention campaign recommending BRCA1 and BRCA2 mutation screening for all high-grade serous cancer patients. METHODS: We conducted a population-based retrospective study in the province of British Columbia, Canada that included all patients visiting the Hereditary Cancer Program for genetic counselling for BRCA1 and BRCA2 mutation between 2001 and 2014. We examined the difference in rates of BRCA1 and BRCA2 testing between serous cancer patients and endometrioid and clear cell cancer patients using a differences in differences analysis. We also calculated the mean number of family members tested for every BRCA1 and BRCA2 identified ovarian cancer patient before and after the educational campaign. RESULTS: There were 5712 women tested for a BRCA1 and BRCA2 mutation at the HCP between 2001 and 2014, 887 of which had previously received a diagnosis of ovarian cancer. By 2013, 43% of serous cancer patients were being tested for BRCA1 and BRCA2 mutations compared with 20% of endometrioid and clear cell patients (p < 0.001). The mean number of family members tested for each BRCA1 and BRCA2 positive ovarian cancer patient increased after the educational campaign from 2.54 to 3.27 (p = 0.071), and the number of family members identified as BRCA positive also increased significantly. CONCLUSIONS: Recommendations for histology-based referral significantly increased the likelihood of serous cancer patients being tested for BRCA mutations. There was also an increase in the number of carrier tests performed for each BRCA1 and BRCA2 index ovarian cancer patient.

Extending the safety evidence for opportunistic salpingectomy in prevention of ovarian cancer: a cohort study from British Columbia, Canada.

BACKGROUND: Recent evidence has suggested that the fallopian tube may often be the site of origin for the most common and lethal form of ovarian cancer. As a result, many Colleges of Obstetrics and Gynecology, including the American College of Obstetricians and Gynecology, are recommending surgical removal of the fallopian tube (bilateral salpingectomy) at the time of other gynecologic surgeries (particularly hysterectomy and tubal sterilization) in women at general population risk for ovarian cancer, collectively referred to as opportunistic salpingectomy. OBJECTIVE: Previous research with the use of hospital data has indicated good perioperative safety of opportunistic salpingectomy, but no data on minor complications have been presented. Herein, we examine whether women who undergo opportunistic salpingectomy are at increased risk of minor complications after surgery. STUDY DESIGN: We identified all women in British Columbia who underwent opportunistic salpingectomy between 2008 and 2014 and examined all physician visits in the 2 weeks after discharge from the hospital. We compared women who underwent opportunistic salpingectomy at hysterectomy with women who underwent hysterectomy alone and women who underwent opportunistic salpingectomy for sterilization with women who underwent tubal ligation. We examined visits for surgical infection, surgical complication, orders for laboratory tests, and orders for imaging (x-ray, ultrasound scan, or computed tomography scan) and whether women who underwent opportunistic salpingectomy were more likely to fill a prescription for an antibiotic or analgesic in the 2 weeks after discharge from the hospital. We calculated adjusted odds ratios for these outcomes, adjusting for other gynecologic conditions, surgical approach, and patient age. RESULTS: We included 49,275 women who had undergone a hysterectomy alone, a hysterectomy with opportunistic salpingectomy, a hysterectomy with bilateral salpingo-oophorectomy, a tubal ligation, or an opportunistic salpingectomy for sterilization. In women who had undergone opportunistic salpingectomy, there was no increased risk for physician visits for surgical infection, surgical complication, ordering a laboratory test, or ordering imaging in the 2 weeks after discharge. There was no increased risk of filling a prescription for an antibiotic. However, women who underwent opportunistic salpingectomy were at approximately 20% increased odds of filling a prescription for an analgesic in the 2 weeks after discharge from the hospital (adjusted odds ratio, 1.23; 95% confidence interval, 1.15-1.32 for hysterectomy with opportunistic salpingectomy; adjusted odds ratio, 1.21; 95% confidence interval, 1.14-1.29 for opportunistic salpingectomy for sterilization). CONCLUSION: We report no differences in minor complications between women who undergo opportunistic salpingectomy and women who undergo hysterectomy alone or tubal ligation, except for a slightly increased likelihood of filling a prescription for analgesic medication in the immediate 2 weeks after discharge.

Changing Clinical Practice: Evaluation of Implementing Recommendations for Opportunistic Salpingectomy in British Columbia and Ontario.

OBJECTIVE: The aim of the study was to explore the factors that contributed to the adoption of opportunistic salpingectomies (removal of fallopian at the time of hysterectomy or in lieu of tubal ligation) by gynecologic surgeons in British Columbia (where a knowledge translation initiative took place) and in Ontario (a comparator where no knowledge translation initiative took place). We aimed to understand why the knowledge translation initiative undertaken by OVCARE in British Columbia resulted in such a dramatic uptake in opportunistic salpingectomy. METHODS: We undertook a qualitative evaluation of clinicians' decisions about whether or not they should adopt the practice of opportunistic salpingectomy based on interviews with gynecologic surgeons in British Columbia and Ontario (n = 28). The analysis draws from the Consolidated Framework for Implementation Research. RESULTS: Regional cohesion combined with practice change information exposure and thought leader support were important in explaining differences in adoption levels between participants. The British Columbian knowledge translation campaign was successful because provincial thought leaders exposed gynecologic surgeons to recommendations through multiple sources within a highly socially cohesive environment wherein clinicians felt pressure to adopt the recommendations. In both provinces, high adopters often believed that the workload and surgical risk associated with the adoption was low and the potential benefit-because of limited ovarian cancer detection and treatment options-was high. CONCLUSION: This research points to the important role that local professional networks can play in encouraging clinicians to change their practice by creating a cohesive regional environment where clinicians are repeatedly exposed to important information and supported in their practice change by local thought leaders.

Outcomes of Conservative Management of High Grade Squamous Intraepithelial Lesions in Young Women.

OBJECTIVE: The aim of the study was to determine regression rates of cervical intraepithelial neoplasia (CIN) 2 and 3 in women younger than 24 years, followed conservatively for up to 24 months. MATERIALS AND METHODS: This is a retrospective chart review of colposcopy patients in clinic database based on the following: (1) younger than 24 years at first visit; (2) first visit January 1, 2010, to May 31, 2013, and at least 1 follow-up visit after diagnosis; (3) histologic diagnosis of CIN2+; and (4) optimal conservative management (observation for up to 24 months or to 24 years, whichever occurred first). Patient information and clinical/pathologic data were extracted from charts to examine patient characteristics and treatment outcomes, CIN2+ regression rates, median times to regression for CIN2 versus CIN3 (Kaplan-Meier survival analysis), and predictors of regression (multivariate logistic regression analysis). RESULTS: A total of 154 women met criteria. The most severe histological diagnoses were CIN2 in 99 (64.3%), CIN3 in 51 (33.1%), and adenocarcinoma in situ in 4 (2.6%). Adenocarcinoma in situ was immediately treated. In follow-up, CIN2 regressed to CIN1 or negative in 74 women (74.7%)-median time to regression, 10.8 months. Cervical intraepithelial neoplasia 3 regressed in 11 women (21.6%)-median time to regression not reached (last follow-up censored at 52.7 months). Cervical intraepithelial neoplasia 2 on biopsy, low grade referral Pap, and younger age predicted regression. Overall, 49 women (31.8%) were treated. CONCLUSIONS: Conservative management should continue to be recommended to young women with CIN2. Rigorous retention mechanisms are required to ensure that these women return for follow-up.

Human papillomavirus (HPV)-independent vulvar squamous cell carcinoma has a worse prognosis than HPV-associated disease: a retrospective cohort study.

AIMS: Vulvar squamous cell carcinoma (VSCC) can be subdivided by human papillomavirus (HPV) status into two clinicopathological entities. Studies on the prognostic significance of HPV in VSCC are discordant. METHODS AND RESULTS: We performed a retrospective analysis of overall survival (OS), disease-specific survival (DSS) and progression-free survival (PFS) in 217 patients with VSCC. Cases were extracted from an era of more aggressive en-bloc radical dissections (1985-95) and more localized radical surgery through separate vulvar and groin excisions (1996-2005). p16 immunohistochemistry was used as a surrogate for HPV status. HPV status could be determined in 197 tumours, 118 HPV-independent and 79 HPV-associated tumours. Patients with HPV-associated tumours were younger (mean 58.8 versus 71.6 years for HPV-independent tumours, P < 0.0001) and more likely to have prior abnormal cervical cytology (41.1 versus 5.6% for HPV-independent tumours, P < 0.0001). In univariable analysis, patients with HPV-associated tumours had superior PFS [hazard ratio (HR): 0.37, 95% confidence interval (CI): 0.18-0.70], DSS (HR: 0.19, 95% CI: 0.08-0.41) and OS (HR: 0.35, 95% CI: 0.21-0.59). This was driven by worse outcomes (PFS, DSS and OS) for patients with HPV-independent tumours compared with HPV-associated tumours who underwent surgery after 1995. After adjusting for age and stage in multivariable analysis, patients with HPV-associated tumours showed superior PFS (HR: 0.25, 95% CI: 0.07-0.77) and DSS (HR: 0.21, 95% CI: 0.04-0.78). CONCLUSIONS: VSCC can be stratified into two prognostically different diseases based on p16 immunostaining. HPV status was associated only with prognosis in the cohort that underwent surgery after 1995, suggesting that more conservative surgery may have led to worse outcomes for patients with HPV-independent tumours.

The performance and safety of bilateral salpingectomy for ovarian cancer prevention in the United States.

BACKGROUND: Ovarian cancer is the leading cause of death due to gynecologic malignancy and the fifth most common cause of cancer deaths in developed countries. Recent evidence has indicated that the most common and lethal form of ovarian cancer originates in the distal fallopian tube, and recommendations for surgical removal of the fallopian tube (bilateral salpingectomy) at the time of other gynecologic surgeries (particularly hysterectomy and tubal sterilization) have been made, most recently by the American Congress of Obstetricians and Gynecologists. OBJECTIVE: We sought to assess the uptake and perioperative safety of bilateral salpingectomy at the time of hysterectomy and tubal sterilization in the United States and to examine the factors associated with increased likelihood of bilateral salpingectomy. STUDY DESIGN: The Nationwide Inpatient Sample was used to identify all girls and women 15 years or older without gynecologic cancer who underwent inpatient hysterectomy or tubal sterilization, with and without bilateral salpingectomy, from 2008 through 2013. Weighted estimates of national rates of these procedures were calculated and the number of procedures performed estimated. Safety was assessed by examining rates of blood transfusions, perioperative complications, postprocedural infection, and fever, and adjusted odds ratios were calculated comparing hysterectomy with salpingectomy with hysterectomy alone. RESULTS: We included 425,180 girls and women who underwent inpatient hysterectomy from 2008 through 2013 representing a national cohort of 2,036,449 (95% confidence interval, 1,959,374-2,113,525) girls and women. There was an increase in the uptake of hysterectomy with bilateral salpingectomy of 371% across the study period, with 7.7% of all hysterectomies including bilateral salpingectomy in 2013 (15.8% among girls and women retaining their ovaries). There were only 1195 salpingectomies for sterilization, thus no further comparisons were possible. In the girls and women who had hysterectomy with bilateral salpingectomy, there was no increased risk for blood transfusion (adjusted odds ratio, 0.95; 95% confidence interval, 0.86-1.05) postoperative complications (adjusted odds ratio, 0.97; 95% confidence interval, 0.88-1.07), postoperative infections (adjusted odds ratio, 1.26; 95% confidence interval, 0.90-1.78), or fevers (adjusted odds ratio, 1.33; 95% confidence interval, 1.00-1.77) compared with women undergoing hysterectomy alone. Younger age, private for-profit hospital setting, larger hospital size, and indication for hysterectomy were all associated with increased likelihood of getting a hysterectomy with bilateral salpingectomy in women retaining their ovaries. CONCLUSION: Our results suggest that hysterectomy with bilateral salpingectomy is significantly increasing in the United States and is not associated with increased risks of postoperative complications.

HPV-independent Differentiated Vulvar Intraepithelial Neoplasia (dVIN) is Associated With an Aggressive Clinical Course.

Differentiated vulvar intrapeithelial neoplasia (dVIN) is an human papillomavirus (HPV)-independent precursor of squamous cell carcinoma (SCC), and the aim of this study was to better characterize its natural history. Cases of dVIN were identified from the pathology archives. Outcomes of patients with dVIN only, without associated invasive SCC, were compared with a cohort of patients with high-grade squamous intraepithelial lesion [HSIL(VIN3)]. Eighteen patients diagnosed with dVIN with adjacent invasive SCC (SCC/dVIN) and 7 patients with dVIN only, without invasive carcinoma, were identified. Mean age in both cohorts was 75 yr. All lesions but 1 were unifocal. In 35% of SCC/dVIN cases the surgical resection margins were positive for SCC, with 75% and 60% having margins positive for dVIN in the SCC/dVIN and dVIN-only cohorts, respectively. In total, 23/25 women with dVIN only or dVIN/SCC, for whom there was follow-up information, experienced either progression to or recurrence of invasive SCC, respectively, at a median of 1.1 yr, including all but 1 case of dVIN only, where the median time of progression to invasive SCC was 1.9 yr. A total of 22/25 women died of disease with a median overall survival of 3.4 yr. The outcome (i.e. progression to invasive carcinoma) of patients with dVIN only was significantly worse than that of a comparison group of 18 patients with HSIL(VIN3) (progression-free survival log-rank, P<0.001; disease-specific survival, P=0.04; overall survival, P=0.01). Six of 7 patients with dVIN only developed invasive carcinoma on follow-up, compared with 0 of 18 patients with HSIL(VIN3). The diagnosis of dVIN indicates the presence of a high-risk human papillomavirus-negative precursor of invasive SCC. These patients are likely to progress to invasive carcinoma over a relatively short period, at which point their prognosis is guarded.

Integrating Quantitative and Qualitative Methods to Evaluate an Online Psychoeducational Program for Sexual Difficulties in Colorectal and Gynecologic Cancer Survivors.

Sexual health is an integral component of quality of life for cancer survivors, and is often negatively impacted by treatment. Geographic limitations often prohibit survivors from accessing sexual health programs designed to address their needs. This study examined the efficacy of an online, 12-week psychoeducational program, which included elements of mindfulness meditation, for sexual difficulties in survivors of colorectal or gynecologic cancer. Complete pre- and postintervention data were available for 46 women (mean age 55.0, SD 9.6) and 15 men (mean age 59.7, SD 6.8). Women experienced significant improvements in sex-related distress (p < .001), sexual function (p < .001 and p < .01), and mood (p < .001); these results were maintained at six months follow-up. Men's improvement in desire was not significant (p = .06), whereas intercourse satisfaction was (p < .05) immediately after the program, but not at follow-up. In order to more fully explore women's experiences, interviews were carried out with six participants and analyzed using narrative inquiry. Women shared a feeling of renewed hope for regaining their sex lives, and expressed that they would have valued an interactive component to the program. These findings suggest that an online, unidirectional psychoeducational program is feasible, and may be effective for women survivors of gynecologic and colorectal cancer, but further work is needed to ensure that online interventions address the sexual health needs of male survivors.

Reduction in cervical intraepithelial neoplasia in young women in British Columbia after introduction of the HPV vaccine: An ecological analysis.

We report on the rates of cervical intraepithelial neoplasia (CIN) in young women aged 15-22 years of age in British Columbia before and after the introduction of an HPV vaccine program. Rates of cervical intraepithelial neoplasia (CIN) 2+ for each age stratum (15-22) in the calendar years 2004-2012 for the province of British Columbia were obtained from the BC Cancer Agency's population-based cervical cancer program. Incidence rate ratios (IRR) of CIN2+ were described and compared before and after HPV vaccine program introduction in cohorts born in vaccine eligible years, and in non-vaccine eligible years using piece-wise Poisson regression analysis, and adjusted for age. Between 2004 and 2012, rates of CIN2 and CIN2+ in young women aged 15-22 years in the province of British Columbia have decreased overall. After the introduction of the HPV vaccine program, the age adjusted IRR for CIN2+ for young women aged 15-17 years decreased significantly from 0.91 (95% CI: 0.86-0.98 p < 0.01) to 0.36 (95% CI: 0.18-0.73 p < 0.01). During the same time period, no similar reduction was found in young women 18-22 years. After introduction of HPV vaccine program, IRR for CIN2+ in young women 15-17 was significantly reduced for CIN2+ (0.14; 95% CI: 0.04- 0.47; p < 0.01) and CIN2 (0.1; 95% CI: 0.02-0.54; p < 0.01). This ecological analysis shows a significant reduction in CIN2+ lesions in young women aged 15-17 years in British Columbia after the introduction of the HPV vaccine in young women despite vaccine uptake levels below 70%.

Vulvar Acanthosis With Altered Differentiation (VAAD): Report of a Case With Progression to Poorly Differentiated Carcinoma Over a 5-Yr Period.

Vulvar acanthosis with altered differentiation is an uncommon proliferation of the vulvar squamous epithelium that is typically seen in association with verrucous carcinoma, and may represent an early phase of non-HPV-related squamous neoplastic transformation. We report a case of vulvar acanthosis with altered differentiation that, over a 5-yr period, progressed first to verrucous carcinoma in association with well-differentiated invasive squamous cell carcinoma and then, after treatment with radiotherapy, to poorly differentiated carcinoma with a component of anaplastic carcinoma. This case supports the concept of vulvar acanthosis with altered differentiation as a premalignant lesion, with potential to progress to invasive carcinoma.

Quantification of confocal fluorescence microscopy for the detection of cervical intraepithelial neoplasia.

BACKGROUND: Cervical cancer remains a major health problem, especially in developing countries. Colposcopic examination is used to detect high-grade lesions in patients with a history of abnormal pap smears. New technologies are needed to improve the sensitivity and specificity of this technique. We propose to test the potential of fluorescence confocal microscopy to identify high-grade lesions. METHODS: We examined the quantification of ex vivo confocal fluorescence microscopy to differentiate among normal cervical tissue, low-grade Cervical Intraepithelial Neoplasia (CIN), and high-grade CIN. We sought to (1) quantify nuclear morphology and tissue architecture features by analyzing images of cervical biopsies; and (2) determine the accuracy of high-grade CIN detection via confocal microscopy relative to the accuracy of detection by colposcopic impression. Forty-six biopsies obtained from colposcopically normal and abnormal cervical sites were evaluated. Confocal images were acquired at different depths from the epithelial surface and histological images were analyzed using in-house software. RESULTS: The features calculated from the confocal images compared well with those features obtained from the histological images and histopathological reviews of the specimens (obtained by a gynecologic pathologist). The correlations between two of these features (the nuclear-cytoplasmic ratio and the average of three nearest Delaunay-neighbors distance) and the grade of dysplasia were higher than that of colposcopic impression. The sensitivity of detecting high-grade dysplasia by analysing images collected at the surface of the epithelium, and at 15 and 30 µm below the epithelial surface were respectively 100, 100, and 92 %. CONCLUSIONS: Quantitative analysis of confocal fluorescence images showed its capacity for discriminating high-grade CIN lesions vs. low-grade CIN lesions and normal tissues, at different depth of imaging. This approach could be used to help clinicians identify high-grade CIN in clinical settings.

Experiencing Health Advocacy During Cervical Cancer Awareness Week: A National Initiative for Obstetrics and Gynaecology Residents.

OBJECTIVE: The Royal College of Physicians and Surgeons of Canada requires that residents demonstrate competence in health advocacy (HA). We sought to develop and implement a national educational module for obstetrics and gynaecology residents to address the role of HA. This pilot program was centred on cervical cancer prevention, which lends itself to applying the principles of advocacy. METHODS: An educational module was developed and disseminated to all obstetrics and gynaecology residency programs in Canada. The module describes options for HA involving cervical dysplasia screening, such as an outreach clinic or a forum for public/student education, which were to be implemented during Cervical Cancer Awareness Week. The measures of success were the number of programs implementing the curriculum, number of residents who participated, diversity of projects implemented, individuals (patients or learners) reached by the program, and the overall experience of the trainees. RESULTS: Three programs implemented the curriculum in 2011, one in 2012, and seven in 2013. After three years, the module has involved seven of 16 medical schools, over 100 residents, and thousands of women either directly or indirectly. Additionally, attributes of HA experienced by the residents were identified: teamwork, leadership, increased systems knowledge, increased social capital within the community, creativity, innovation, and adaptability. CONCLUSION: We have demonstrated that an educational module can be implemented nationally, helping our residents fulfill their HA requirements. Other specialties could use this module in building HA into their own programs.

Objectif : Le Collège royal des médecins et chirurgiens du Canada exige que les résidents fassent preuve de compétence dans le rôle de promoteur de la santé (PS ou promotion de la santé). Nous avons cherché à élaborer et à mettre en œuvre, à l'intention des résidents en obstétrique-gynécologie, un module pédagogique national traitant de ce rôle de PS. Ce programme pilote était centré sur la prévention du cancer du col utérin, soit un sujet se prêtant bien à l'application des principes de la promotion de la santé. Méthodes : Un module pédagogique a été élaboré et transmis à tous les programmes de résidence en obstétrique-gynécologie au Canada. Ce module décrit les options de PS mettant en jeu le dépistage de la dysplasie cervicale (telles qu'une clinique visant l'élargissement de la population desservie ou un forum d'éducation visant le public / la population étudiante) qui devaient être mises en œuvre au cours de la Semaine de sensibilisation au cancer du col de l'utérus. La réussite a été mesurée en fonction du nombre de programmes mettant en œuvre le curriculum, du nombre de résidents y ayant participé, de la diversité des projets mis en œuvre, de la nature des personnes (patientes ou apprenants) atteintes par le programme et de l'expérience globale des stagiaires. Résultats : Trois programmes ont mis en œuvre le curriculum en 2011, un programme l'a fait en 2012 et sept l'ont fait en 2013. Après trois ans, le module s'est attiré la participation directe ou indirecte de sept des 16 facultés de médecine, de plus de 100 résidents et de milliers de femmes. De plus, les attributs de la PS vécus par les résidents ont été identifiés : travail d'équipe, leadership, connaissances accrues au sujet des systèmes, capital social accru au sein de la communauté, créativité, innovation et adaptabilité. Conclusion : Nous avons démontré qu'un module pédagogique, visant à aider nos résidents à répondre à leurs exigences en matière de PS, peut être mis en œuvre à l'échelle nationale. D'autres spécialités pourraient utiliser ce module pour incorporer la PS dans leurs programmes respectifs.

Projected Impact of HPV and LBC Primary Testing on Rates of Referral for Colposcopy in a Canadian Cervical Cancer Screening Program.

OBJECTIVE: To estimate the impact of implementing primary human papilloma virus liquid-based cytology (LBC) screening on four-year rates of referral for colposcopy in the British Columbia screening program. METHODS: We used data on referral for colposcopy from an RCT (HPV FOCAL) comparing HPV testing every four years with LBC testing every two years. We also used data from population screening with conventional cytology among women aged 25 to 69. The predicted effect of adoption of either trial protocol on rates of referral for colposcopy was estimated using trial age-specific result and screening result-specific rates weighted by their screening program distribution. The cumulative age-specific rates of referral for colposcopy over four years were calculated. RESULTS: Use of HPV testing initially increased rates of referral for colposcopy in the trial, but over four years the cumulative rates of referral were similar to those for LBC except in women aged 25 to 29, in whom a substantial excess persisted. Four-year rates of referral for colposcopy declined with age in women screened with HPV testing, LBC, and conventional cytology. Extrapolating the trial results to the distribution in the provincial screening program, implementation of either HPV or LBC throughout the provincial population would approximately double the current rates of referral for colposcopy. CONCLUSION: Compared with LBC screening, primary screening for HPV increased rates of referral for colposcopy only among women aged 25 to 29. In contrast to current practice, referral for colposcopy was largely driven by the trial protocol recommendations for the management of abnormal results and not by which screening test was used.

Objectif : Estimer les effets de la mise en œuvre d'un dépistage primaire du virus du papillome humain par cytologie en milieu liquide (CML) sur les taux d'orientation en colposcopie sur quatre ans, dans le cadre du programme de dépistage de la Colombie-Britannique. Méthodes : Nous avons utilisé les données sur l'orientation en colposcopie issues d'un ECR (HPV FOCAL) comparant le dépistage du VPH tous les quatre ans au dépistage par CML tous les deux ans. Nous avons également utilisé des données issues du dépistage populationnel par cytologie conventionnelle mené auprès des femmes de 25 à 69 ans. Le taux d'orientation en colposcopie en fonction de l'âge et le taux d'orientation en colposcopie en fonction des résultats de dépistage ont été pondérés en fonction de la distribution de leurs programmes de dépistage respectifs, ce qui a permis d'estimer l'effet populationnel prévu de l'adoption de l'un ou l'autre des protocoles d'essai en question sur les taux d'orientation en colposcopie. Les taux cumulatifs (en fonction de l'âge) de l'orientation en colposcopie sur quatre ans ont été calculés. Résultats : Le recours au dépistage du VPH a initialement mené à la hausse des taux d'orientation en colposcopie dans le cadre de l'essai; toutefois, sur quatre ans, les taux cumulatifs d'orientation ont été semblables à ceux de la CML, sauf chez les femmes de 25 à 29 ans (chez lesquelles un excès substantiel a persisté). Les taux d'orientation en colposcopie sur quatre ans ont connu une baisse en fonction de l'âge chez les femmes ayant fait l'objet d'un dépistage du VPH, d'une CML et d'une cytologie conventionnelle. En extrapolant les résultats de l'essai à la distribution qui existe au sein du programme provincial de dépistage, nous avons constaté que la mise en œuvre du dépistage du VPH ou de la CML au sein de la population provinciale mènerait au doublement approximatif des taux actuels d'orientation en colposcopie. Conclusion : Par comparaison avec le dépistage par CML, le dépistage primaire du VPH n'a entraîné la hausse des taux d'orientation en colposcopie que chez les femmes de 25 à 29 ans. Contrairement à la pratique actuelle, l'orientation en colposcopie était largement motivée par les recommandations du protocole d'essai en ce qui concerne la prise en charge des résultats anormaux, et non par le test de dépistage utilisé.

Opportunistic salpingectomy: uptake, risks, and complications of a regional initiative for ovarian cancer prevention.

OBJECTIVE: The purpose of this study was to assess the uptake and perioperative safety of bilateral salpingectomy (BS) as an ovarian cancer risk-reduction strategy in low-risk women after a regional initiative that was aimed at general gynecologists in the province of British Columbia, Canada. STUDY DESIGN: This population-based retrospective cohort study evaluated 43,931 women in British Columbia from 2008-2011 who underwent hysterectomy that was performed with and without BS or bilateral salpingo-oophorectomy or who underwent surgical sterilization by means of BS or tubal ligation. Parameters that were examined include patient age, operating time, surgical approach, indication, length of hospital stay, and perioperative complications. RESULTS: There was an increase in the uptake of hysterectomy with BS (5-35%; P < .001) and BS for sterilization (0.5-33%; P < .001) over the study period, particularly in women <50 years old. Minimal additional surgical time is required for hysterectomy with BS (16 minutes; P < .001) and BS for sterilization (10 minutes; P < .001) compared with hysterectomy alone or tubal ligation, respectively. No significant differences were observed in the risks of hospital readmission or blood transfusions in women who underwent hysterectomy with BS (adjusted odds ratio [aOR], 0.91; 95% confidence interval [CI], 0.75-1.10; and aOR, 0.86; 95% CI, 0.67-1.10, respectively) or BS for sterilization (aOR, 0.8; 95% CI, 0.56-1.21; and aOR, 0.75; 95% CI, 0.32-1.73, respectively). From 2008-2011 the proportion of hysterectomies with BS performed by open laparotomy decreased from 77-44% with uptake in laparoscopic, vaginal, and combined procedures (P < .001). CONCLUSION: After our 2010 educational initiative, there has been a shift in surgical paradigm in our province. This cancer prevention approach does not increase the risk of operative/perioperative complications and appears both feasible and safe.

Molecular fixative enables expression microarray analysis of microdissected clinical cervical specimens.

Formalin-fixed tissue has been a mainstay of clinical pathology laboratories, but formalin alters many biomolecules, including nucleic acids and proteins. Meanwhile, frozen tissues contain better-preserved biomolecules, but tissue morphology is affected, limiting their diagnostic utility. Molecular fixatives promise to bridge this gap by simultaneously preserving morphology and biomolecules, enabling clinical diagnosis and molecular analyses on the same specimen. While previous reports have broadly evaluated the use of molecular fixative in various human tissues, we present here the first detailed assessment of the applicability of molecular fixative to both routine histopathological diagnosis and molecular analysis of cervical tissues. Ten specimens excised via the loop electrosurgical excision procedure, which removes conical tissue samples from the cervix, were cut into alternating pieces preserved in either formalin or molecular fixative. Cervical specimens preserved in molecular fixative were easily interpretable, despite featuring more eosinophilic cytoplasm and more recognizable chromatin texture than formalin-fixed specimens. Immunohistochemical staining patterns of p16 and Ki-67 were similar between fixatives, although Ki-67 staining was stronger in the molecular fixative specimens. The RNA of molecular fixative specimens from seven cases representing various dysplasia grades was assessed for utility in expression microarray analysis. Cluster analysis and scatter plots of duplicate samples suggest that data of sufficient quality can be obtained from as little as 50ng of RNA from molecular fixative samples. Taken together, our results show that molecular fixative may be a more versatile substitute for formalin, simultaneously preserving tissue morphology for clinical diagnosis and biomolecules for immunohistochemistry and gene expression analysis.

ARID1A mutations in endometriosis-associated ovarian carcinomas.

BACKGROUND: Ovarian clear-cell and endometrioid carcinomas may arise from endometriosis, but the molecular events involved in this transformation have not been described. METHODS: We sequenced the whole transcriptomes of 18 ovarian clear-cell carcinomas and 1 ovarian clear-cell carcinoma cell line and found somatic mutations in ARID1A (the AT-rich interactive domain 1A [SWI-like] gene) in 6 of the samples. ARID1A encodes BAF250a, a key component of the SWI­SNF chromatin remodeling complex. We sequenced ARID1A in an additional 210 ovarian carcinomas and a second ovarian clear-cell carcinoma cell line and measured BAF250a expression by means of immunohistochemical analysis in an additional 455 ovarian carcinomas. RESULTS: ARID1A mutations were seen in 55 of 119 ovarian clear-cell carcinomas (46%), 10 of 33 endometrioid carcinomas (30%), and none of the 76 high-grade serous ovarian carcinomas. Seventeen carcinomas had two somatic mutations each. Loss of the BAF250a protein correlated strongly with the ovarian clear-cell carcinoma and endometrioid carcinoma subtypes and the presence of ARID1A mutations. In two patients, ARID1A mutations and loss of BAF250a expression were evident in the tumor and contiguous atypical endometriosis but not in distant endometriotic lesions. CONCLUSIONS: These data implicate ARID1A as a tumor-suppressor gene frequently disrupted in ovarian clear-cell and endometrioid carcinomas. Since ARID1A mutation and loss of BAF250a can be seen in the preneoplastic lesions, we speculate that this is an early event in the transformation of endometriosis into cancer. (Funded by the British Columbia Cancer Foundation and the Vancouver General Hospital­University of British Columbia Hospital Foundation.).