Access to Surgery for Endometrial Cancer Patients During the COVID-19 Pandemic in Ontario, Canada: A Population-Based Study.

OBJECTIVES: To assess the impact of the COVID-19 pandemic on endometrial cancer stage and surgical treatment in Ontario, Canada. METHODS: This descriptive study identified cases from January 1, 2017 to December 31, 2021 from endometrial cancer hysterectomy specimens in the Ontario Health-Cancer Care Ontario, ePath system. Endometrial biopsy records from January 1, 2016 to December 31, 2021 were matched to surgical specimens by provincial health card number. Time to surgery and surgical stage were compared before (2017-2019) and during (2020-2021) the COVID-19 pandemic. RESULTS: There were 10 446 women treated with hysterectomy for endometrial cancer in Ontario from 2017-2021. In April and May 2020, corresponding with the provincial state of emergency, there was a 56% relative reduction in endometrial biopsies. Despite this 2-month reduction in endometrial biopsy volume, there was no change in surgical volume for endometrial cancer treatment. The median time from endometrial biopsy to surgery was 56 days (IQR 40, 80) during the pandemic (2020-2021) compared to 58 days (IQR 43, 82) prior to the pandemic (2017-2019) (P < 0.001). There was no upstaging of endometrial cancer during the COVID-19 pandemic. CONCLUSIONS: The Ontario healthcare system continued to prioritize service delivery to endometrial cancer patients during the COVID-19 pandemic, despite the increase in virtual care and decrease in operating room time. There were no significant surgical delays or upstaging of endometrial cancer.

Defining the Longitudinal Risk of CIN 3+ for

OBJECTIVE: To determine the baseline and cumulative risk of cervical intraepithelial neoplasia (CIN)3 and invasive cervical cancer in participants referred to colposcopy with high-grade cytology and

Mesonephric-like adenocarcinoma of the female genital tract: novel observations and detailed molecular characterisation of mixed tumours and mesonephric-like carcinosarcomas.

AIMS: To report novel observations in five mesonephric-like adenocarcinomas (MLAs) of the female genital tract. METHODS AND RESULTS: We report two endometrial MLAs in association with endometrioid carcinoma and atypical hyperplasia and three (one endometrial, two ovarian) cases with a sarcomatoid component (mesonephric-like carcinosarcoma). Pathogenic KRAS mutations, which are characteristic of MLA, were identified in all cases although interestingly, in one of the mixed carcinomas, this was confined to the endometrioid component. The concurrent MLA, endometrioid carcinoma and atypical hyperplasia components in one case harboured identical EGFR, PTEN and CCNE1 mutations, suggesting that the atypical hyperplasia gave rise to a Müllerian carcinoma with both endometrioid and mesonephric-like components. The carcinosarcomas all contained a component of MLA and a sarcomatous component with chondroid elements. In the ovarian carcinosarcomas, the coexisting epithelial and sarcomatous components shared some mutations including KRAS and CREBBP, suggesting that they are clonally related. Furthermore, in one case CREBBP and KRAS mutations detected in the MLA and sarcomatous components were also detected in an associated undifferentiated carcinoma component, suggesting that it was clonally related to the MLA and sarcomatous components. CONCLUSIONS: Our observations provide additional evidence that MLAs have a Müllerian origin and characterise mesonephric-like carcinosarcomas in which chondroid elements appear to be characteristic. In reporting these findings, we provide recommendations for distinction between a mesonephric-like carcinosarcoma and a MLA with a spindle cell component.

Apixaban for extended postoperative thromboprophylaxis in gynecologic oncology patients undergoing laparotomy.

INTRODUCTION: Venous thromboembolic events represent the second most frequent cause of mortality in cancer patients. Recent literature shows that direct oral anticoagulants (DOAC) are at least as effective and safe as low molecular weight heparin for postoperative thromboprophylaxis. However, this practice has not been broadly adopted in gynecologic oncology. The aim of this study was to evaluate clinical effectiveness and safety of apixaban for extended thromboprophylaxis in comparison to enoxaparin after laparotomies for gynecologic oncology patients. METHODS: The Gynecologic Oncology Division at a large tertiary center transitioned from enoxaparin 40 mg daily to apixaban 2.5 mg BID for 28 days after laparotomies for gynecologic malignancies in November 2020. This real-world study compared patients post-transition (November 2020 to July 2021 (n = 112)) to a historical cohort (January to November 2020 (n = 144)), using the institutional National Surgical Quality Improvement Program (NSQIP) database. All Canadian gynecologic oncology centers were surveyed to assess postoperative DOAC utilization. RESULTS: Patient characteristics were similar between groups. No difference was found between total venous thromboembolism rates (4% vs. 3%, p = 0.49). No difference was found in postoperative readmission (5% vs. 6%, p = 0.50). Of the 7 readmissions in the enoxaparin group, one was due to bleeding requiring transfusion; there were no readmissions for bleeding in the apixaban group. No patient required a reoperation for bleeding. Thirteen percent of the 20 Canadian centers have transitioned to extended apixaban thromboprophylaxis. CONCLUSIONS: Apixaban for 28-day postoperative thromboprophylaxis was found to be an effective and safe alternative to enoxaparin after laparotomies in a real-world cohort of gynecologic oncology patients.

Role of HPV in the Prediction of Persistence/Recurrence After Treatment for Cervical Precancer.

OBJECTIVES: (1) To determine the role of human papillomavirus (HPV) testing after excisional treatment of cervical precancer. (2) To determine clinical factors associated with persistence of cervical precancer post-treatment. METHODS: A retrospective chart review was conducted including patients who had a loop electrosurgical excision procedure (LEEP) for cervical precancer (cervical intraepithelial neoplasia 3/adenocarcinoma in situ/high-grade squamous intraepithelial lesions [HSIL]). All patients treated between 2016 and 2018 at a tertiary centre colposcopy unit were included. Persistence/recurrence of disease was defined as high-grade cytology or histology identified during the time of follow-up. Univariate and multivariate regression models were performed to identify factors associated with persistence/recurrence and HPV positivity at exit testing. RESULTS: A total of 284 patients were included. The median follow-up time was 19 months. Of the LEEP specimens, 90.8% (n = 258) demonstrated HSIL and 3.9% (n = 11) had adenocarcinoma in situ. 28.5% (n = 81) of the LEEP specimens had positive margins. In follow-up, 72.9% had negative cytology, 17.6% had atypical squamous cells of undetermined significance/low-grade SIL, 1.8% had atypical squamous cells, HSIL cannot be excluded/low-grade SIL-H, and 6.7% had HSIL. At the final follow-up, 27.8% (n = 79) were HPV+. Overall rate of persistence/recurrence was 11.3% (n = 32); median time to persistence/recurrence was 6.5 months. Multivariate regression models demonstrated that follow-up HPV positivity (OR = 22.0) and positive margins (OR = 3.7) were significantly associated with persistence/recurrence. Similarly, in univariate regression models, positive margins were significant (OR = 2.2) for predicting HPV positivity in exit testing. CONCLUSIONS: Persistence/recurrence of precancer can occur due to incomplete treatment of lesions by local excision and by the persistence of HPV infection. Surveillance strategies for women treated for cervical precancer require a risk-based approach and should rely on HPV testing.

Pre-operative wait times in high-grade non-endometrioid endometrial cancer: Do surgical delays impact patient survival?

OBJECTIVE: Practice guidelines advocating for regionalization of endometrial cancer surgery to gynecologic oncologists practicing in designated gynecologic oncology centres were published in Ontario in June 2013. Our objectives were to determine whether this policy affected surgical wait times, and whether longer wait time to surgery is a predictor of survival in high grade endometrial cancer patients. METHODS: This was a population-based retrospective cohort study, which included patients diagnosed with high-grade non-endometrioid endometrial cancer who had a hysterectomy between 2003 and 2017. Multivariable Cox proportional hazards regression with a spline function was used to model the relationship between surgical wait time and overall survival (OS). RESULTS: We identified 3518 patients who underwent hysterectomy for high-grade non-endometrioid endometrial cancer. Patients who had surgery with a gynecologic oncologist had a median surgical wait time from diagnosis to hysterectomy of 53 days compared to 57 days pre-regionalization (p = 0.0007), and from first gynecologic oncology consultation to hysterectomy of 29 days compared to 32 days pre-regionalization (p = 0.0006). Survival was inferior for patients who had surgery within 14 days of diagnosis (HR death 2.7 for 1-7 days, 95% CI 1.61-4.51, and HR death 1.96 for 8-14 days, 95% CI 1.50-2.57), reflective of disease severity. Decreased survival occurred with surgical wait times of more than 45 days from the patient's first gynecologic oncology appointment (HR death 1.19 for 46-60 days, 95% CI 1.04-1.36, and HR death 1.42 for 61-75 days, 95% CI 1.11-1.83). CONCLUSIONS: Regionalization of surgery for high-grade endometrial cancer has not had an impact on surgical wait times. Patients who have surgery more than 45 days after surgical consultation have reduced survival.

The accuracy of intraoperative frozen section examination of sentinel lymph nodes in squamous cell cancer of the vulva.

OBJECTIVE: To assess the diagnostic accuracy of intraoperative pathologic examination of sentinel lymph nodes (SLNs) and patient outcomes in vulva cancer. METHODS: This retrospective study included patients with unifocal, <4 cm, invasive vulvar squamous cell carcinoma and clinically negative groin nodes treated with SLN biopsy from January 2008-March 2020. Intraoperative SLN frozen section and final pathology were compared. If the SLN was negative, inguinal femoral lymphadenectomy (IFLD) was omitted. Recurrence location and groin recurrence free survival (RFS) were assessed. RESULTS: The SLN cohort included 173 patients, with 258 groins. On frozen section, there were 36/258 positive and 222 negative groins. On final pathology, there were 39/258 positive: 31 macrometastases, 6 micrometastases, 2 isolated tumor cells (ITCs) and 219 negative groins. The sensitivity, specificity, PPV and NPV for intraoperative detection of metastatic disease, was 89.7% and 99.5%, 97.2% and 98.2%, respectively. There was 1 false positive and 4 false negative frozen section results where final pathology revealed 2 ITCs, 1 micrometastasis and 1 macrometastasis. Based on intraoperative results, thirty patients (17.3%) underwent immediate IFLD. Median follow up was 38.0 (1-137.8) months. The 3-year groin RFS was 91.6% (95% CI 86.2-97.4%) for negative SLNs and 64.6% (95% CI 46.5-89.7%) for positive SLNs on frozen section. Similarly, the 3-year groin RFS was 91.7% (95% CI 86.3-97.4%) for negative, 58.4% (95% CI 38.5-87.7%) for macrometastases and 100% for micrometastases/ITCs on final pathology. CONCLUSIONS: Intraoperative assessment of SLNs is accurate to determine need for IFLD and does not compromise patient outcomes in vulvar cancer.

The role of oophoropexy in patients with gynecological cancer who need radiation therapy.

Pelvic radiotherapy is an essential component of cancer therapy for patients with cervical and other gynecological malignancies. The ovaries are particularly radiosensitive, and even low radiotherapy doses may result in impaired or complete loss of ovarian function, causing hormonal disturbances and infertility. Recent advances in both surgery and radiotherapy have facilitated the ability of some patients to maintain ovarian function through ovarian transposition and careful radiotherapy planning. Multidisciplinary discussions should be undertaken to consider which candidates are appropriate for transposition. Generally, patients under age 35 should be considered due to ovarian reserve, likelihood of oophoropexy success, and radioresistance of ovaries. Those patients with small squamous cell tumors, minimal extra-uterine extension, and no lymphovascular invasion or lymph node involvement are ideal candidates to minimize risk of ovarian metastasis. Patients should be assessed and counseled about the risks of ovarian metastasis and the likelihood of successful ovarian preservation before undergoing oophoropexy and starting treatment. Oophoropexy should be bilateral if possible, and ovaries should be placed superior and lateral to the radiotherapy field. Studies limiting the mean ovarian dose to less than 2-3 Gray have demonstrated excellent preservation of ovarian function. Intensity modulated radiotherapy and volumetric modulated arc therapy techniques have the potential to further minimize the dose to the ovary with excellent outcomes. The addition of brachytherapy to the treatment regimen will probably cause minimal risk to transposed ovaries. Oophoropexy before radiotherapy may preserve the hormonal function of ovaries for a duration, and fertility might be possible through surrogate pregnancy. Successful ovarian transposition has the potential to improve the overall health and wellbeing, reproductive options, and potentially quality of life in patients with cervical and other gynecological cancers.

Dual mechanical and pharmacological thromboprophylaxis decreases risk of pulmonary embolus after laparotomy for gynecologic malignancies.

OBJECTIVES: Patients with gynecologic malignancies have high rates of post-operative venous thromboembolism. Currently, there is no consensus for peri-operative thromboprophylaxis specific to gynecologic oncology. We aimed to compare rates of symptomatic pulmonary embolus within 30 days post-operatively, and to identify risk factors for pulmonary embolus. METHODS: The Division of Gynecologic Oncology at Sunnybrook Health Sciences Centre implemented dual thromboprophylaxis for laparotomies in December 2017. We conducted a prospective study of laparotomies for gynecologic malignancies from December 2017 to October 2018, with comparison to historical cohort from January 2016 to November 2017 using the institutional National Surgical Quality Improvement Program database (NSQIP). Pre-intervention, patients received low molecular weight heparin during admission and extended 28-day prophylaxis was continued at the surgeon's discretion. Post-intervention, all patients received both mechanical thromboprophylaxis with sequential compression devices during admission and 28-day prophylaxis with low molecular weight heparin. RESULTS: There were 371 and 163 laparotomies pre- and post-intervention, respectively. Patient characteristics (age, body mass index, diabetes, smoking, tumor stage), rate of malignant cases, operative blood loss and duration, and length of stay were similar between groups. After implementation, pulmonary emboli rates decreased from 5.1% to 0% (p=0.001). There were more cytoreductive procedures pre-intervention (p≤0.0001) but surgical complexity scores were similar (p=0.82). Univariate analysis revealed that surgery pre-intervention (OR 4.25, 95% CI 1.04 to 17.43, p=0.04), length of stay ≥5 days (OR 11.94, 95% CI 2.65 to 53.92, p=0.002), and operative blood loss ≥500 mL (OR 2.85, 95% CI 1.05 to 7.8, p=0.04) increased risk of pulmonary embolus. On multivariable analysis, surgery pre-intervention remained associated with more pulmonary emboli (OR 4.16, 95% CI 1.03 to 16.79, p=0.045), when adjusting for operative blood loss. CONCLUSION: Dual thromboprophylaxis after laparotomy significantly reduced rates of pulmonary embolus in this high-risk patient population.

Are Women with Antecedent Low-Grade Cytology and <CIN2 Findings in Colposcopy Being Overmanaged?

OBJECTIVE: To determine the baseline and cumulative risks of cervical intraepithelial lesion grade 3 (CIN3) and invasive cervical cancer in patients with <CIN2 colposcopy findings after a low-grade screening cytology finding (atypical squamous cells of undetermined significance or low-grade squamous intraepithelial lesion [LSIL]). METHODS: By linking administrative databases, including cytology, pathology, cancer registries, and physician billing history, a population-based cohort study was performed on participants with <CIN2 initial colposcopy results after a low-grade antecedent cytology finding, between January 2012 and December 2013. Three and 5-year risks of CIN3 and invasive cervical cancer were generated using Kaplan-Meier survival analysis. RESULTS: Among the 36 887 participants included in the study, CIN3 incidence based on referral cytology were as follows at 3 and 5 years, respectively: normal, 0.7% and 0.9%; ASCUS, 4.31% and 5.6%; and LSIL, 5.9% and 7.2%. Three- and 5-year incidence of invasive cancer were 0% and 0.02% for normal cytology, 0.08% and 0.11% for ASCUS, and 0.04% and 0.07% for LSIL, respectively. Stratifying risk by biopsy result at initial colposcopy, 3- and 5-year CIN3 incidences were 2.85% and 3.81% with a negative biopsy, 7.09% and 8.32% with an LSIL biopsy, and 4.11% and 5.2% when no biopsy was done, respectively. Three- and 5-year incidence of invasive cancer was 0% and 0.05% after a negative biopsy, 0% and 0% after LSIL biopsy, and 0.05% and 0.08% when no biopsy was done, respectively. CONCLUSION: When initial colposcopy is done after a low-grade screening cytology result and <CIN2 is identified, the risk of CIN3 and invasive cancer is low, particularly when biopsies indicate LSIL. Surveillance strategies should balance the likelihood of detecting CIN3 with the potential harms over management with too frequent screening or colposcopic interventions in low-risk patients.

Outcomes after the regionalization of care for high-grade endometrial cancers: a population-based study.

BACKGROUND: In June 2013, Ontario Health (Cancer Care Ontario), the agency responsible for advancing cancer care in Ontario, Canada, published practice guidelines recommending that gynecologic oncologists at tertiary care centers manage the treatment of patients with high-grade endometrial cancers. This study examines the effects of this regionalization of care on patient outcomes. OBJECTIVE: This study aimed to evaluate the impact of the regionalization of surgery for high-grade endometrial cancer on patient and treatment outcomes. STUDY DESIGN: In this retrospective cohort study, patients diagnosed with nonendometrioid high-grade endometrial cancer from 2003 to 2017 were identified using province-wide administrative databases. To allow 6 months for knowledge translation, 2 periods were defined, with January 1, 2014, as the cutoff. Methods for segmented regression were used to test the effect of the guidelines. Multivariable Cox proportional hazards regression was used to evaluate whether regionalization of care had an impact on patient survival. RESULTS: There were 3518 patients with nonendometrioid high-grade endometrial cancer identified. The case mix as represented by patient comorbidities and the disease stage distribution did not differ significantly between the 2 regionalization periods. There was a significant increase (69%-85%; P<.001) in the proportion of primary surgeries performed by gynecologic oncologists after regionalization, which was not explained by secular trends. After regionalization, the proportion of patients who had surgical staging (50%-63%; P<.001) and the proportion of patients who received adjuvant treatment (65%-71%; P<.001) increased significantly. After adjusting for age, stage, and comorbidities, there was a decrease in the hazard of mortality (hazard ratio, 0.85 [95% confidence interval, 0.73-0.99]; P=.04) after regionalization. CONCLUSION: The publication of a regionalization policy for the treatment of high-grade endometrial cancers in Ontario led to an increase in the proportion of surgeries performed by gynecologic oncologists. This also translated into a significant improvement in patient survival.

Measuring the impact of the COVID-19 pandemic on organized cancer screening and diagnostic follow-up care in Ontario, Canada: A provincial, population-based study.

It is essential to quantify the impacts of the COVID-19 pandemic on cancer screening, including for vulnerable sub-populations, to inform the development of evidence-based, targeted pandemic recovery strategies. We undertook a population-based retrospective observational study in Ontario, Canada to assess the impact of the pandemic on organized cancer screening and diagnostic services, and assess whether patterns of cancer screening service use and diagnostic delay differ across population sub-groups during the pandemic. Provincial health databases were used to identify age-eligible individuals who participated in one or more of Ontario's breast, cervical, colorectal, and lung cancer screening programs from January 1, 2019-December 31, 2020. Ontario's screening programs delivered 951,000 (-41%) fewer screening tests in 2020 than in 2019 and volumes for most programs remained more than 20% below historical levels by the end of 2020. A smaller percentage of cervical screening participants were older (50-59 and 60-69 years) during the pandemic when compared with 2019. Individuals in the oldest age groups and in lower-income neighborhoods were significantly more likely to experience diagnostic delay following an abnormal breast, cervical, or colorectal cancer screening test during the pandemic, and individuals with a high probability of living on a First Nation reserve were significantly more likely to experience diagnostic delay following an abnormal fecal test. Ongoing monitoring and management of backlogs must continue. Further evaluation is required to identify populations for whom access to cancer screening and diagnostic care has been disproportionately impacted and quantify impacts of these service disruptions on cancer incidence, stage, and mortality. This information is critical to pandemic recovery efforts that are aimed at achieving equitable and timely access to cancer screening-related care.

Cervical conization and lymph node assessment for early stage low-risk cervical cancer.

OBJECTIVE: There has been a contemporary shift in clinical practice towards tailoring treatment in patients with early cervical cancer and low-risk features to non-radical surgery. The objective of this study was to evaluate the oncologic, fertility, and obstetric outcomes after cervical conization and sentinel lymph node (SLN) biopsy in patients with early stage low-risk cervical cancer. METHODS: We conducted a retrospective review in patients with early cervical cancer treated with cervical conization and lymph node assessment between November 2008 and February 2020. Eligibility criteria included patients with a histologic diagnosis of invasive squamous cell carcinoma, adenocarcinoma or adenosquamous carcinoma, International Federation of Gynecology and Obstetrics 2009 stage IA1 with positive lymphovascular space invasion (LVSI), stage IA2, or stage IB1 (≤2 cm) with less than two-thirds (<10 mm) cervical stromal invasion. RESULTS: A total of 44 patients were included in the analysis. The median age was 31 years (range 19-61) and 20 patients (45%) were nulliparous. One patient had a 25 mm tumor while the remaining patients had tumors smaller than 20 mm. Eighteen (41%) patients had LVSI. Median follow-up was 44 months (range 6-137). A total of 17 (39%) patients had negative margins on the diagnostic excisional procedure, and none had residual disease on the repeat cone biopsy. Three (6.8%) patients had micrometastases detected in the SLNs and underwent ipsilateral lymphadenectomy; all remaining non-SLN lymph nodes were negative. Six (13.6%) patients required more definitive surgical or adjuvant treatment due to high-risk pathologic features. There were no recurrences documented. Three patients developed cervical stenosis. The live birth rate was 85% and 16 (94%) of 17 patients had live births at term. CONCLUSION: Cervical conization with SLN biopsy appears to be a safe treatment option in selected patients with early cervical cancer. Future results of prospective trials may shed definitive light on fertility-sparing options in this group of patients.

Survival of Older Women With Cervical Cancer Based on Screening History.

OBJECTIVE: A population-level retrospective cohort study was conducted to determine the influence of cervical screening history on the survival from cervical cancer in women 50 years or older. METHODS: The study included women diagnosed with invasive cervical cancer in Ontario, Canada, between 2005 and 2012, who were followed for at least 4 years. Screening history was observed for the 5 years before diagnosis. Health care administrative databases were linked to determine demographic, affiliation with primary care physicians, stage (available 2010-2012), treatment, and survival data. Kaplan-Meier and multivariate analyses were carried out to evaluate the impact of cervical screening on overall survival (OS). RESULTS: There were eligible 1,422 women diagnosed with invasive cervical cancer between 2005 and 2012 of whom 566 had been screened within the 5 years before diagnosis. There were 856 women who did not undergo screening within the 5 years before diagnosis. Unscreened women were more likely to present with locally advanced disease (69.3%) compared with the screened women (42.9%). Four-year OS was significantly greater in the screened group (79.9% vs 58.2%). In our univariate analysis, screening was significantly related to survival (hazard ratio = 2.1, p < .01). In our multivariate analysis after adjusting for age, treatment, affiliation with a primary care physician, and income, screening was still significantly associated with improved survival (hazard ratio = 1.5, p < .01). CONCLUSIONS: Our results demonstrate a survival benefit to screening in women 50 years or older who are diagnosed with cervical cancer. Screening participation must be encouraged in women older than 50 years as rates decline in this age group.

Survival after minimally invasive surgery in early cervical cancer: is the intra-uterine manipulator to blame?

OBJECTIVES: Minimally invasive radical hysterectomy is associated with decreased survival in patients with early cervical cancer. The objective of this study was to determine whether the use of an intra-uterine manipulator at the time of laparoscopic or robotic radical hysterectomy is associated with inferior oncologic outcomes. METHODS: A retrospective cohort study was carried out of all patients with cervical cancer (squamous cell carcinoma, adenocarcinoma or adenosquamous carcinoma) International Federation of Gynecology and Obstetrics 2009 stages IA1 (with positive lymphovascular space invasion) to IIA who underwent minimally invasive radical hysterectomy at two academic centers between January 2007 and December 2017. Treatment, tumor characteristics, and survival data were retrieved from hospital records. RESULTS: A total of 224 patients were identified at the two centers; 115 had surgery with the use of an intra-uterine manipulator while 109 did not; 53 were robotic and 171 were laparoscopic. Median age was 44 years (range 38-54) and median body mass index was 25.8 kg/m2 (range 16.6-51.5). Patients in whom an intra-uterine manipulator was not used at the time of minimally invasive radical hysterectomy were more likely to have residual disease at hysterectomy (p<0.001), positive lymphovascular space invasion (p=0.02), positive margins (p=0.008), and positive lymph node metastasis (p=0.003). Recurrence-free survival at 5 years was 80% in the no intra-uterine manipulator group and 94% in the intra-uterine manipulator group. After controlling for the presence of residual cancer at hysterectomy, tumor size and high-risk pathologic criteria (positive margins, parametria or lymph nodes), the use of an intra-uterine manipulator was no longer significantly associated with worse recurrence-free survival (HR 0.4, 95% CI 0.2 to 1.0, p=0.05). The only factor which was consistently associated with recurrence-free survival was tumor size (HR 2.1, 95% CI 1.5 to 3.0, for every 10 mm increase, p<0.001). CONCLUSION: After controlling for adverse pathological factors, the use of an intra-uterine manipulator in patients with early cervical cancer who underwent minimally invasive radical hysterectomy was not an independent factor associated with rate of recurrence.

Cervical Screening and Colposcopy Management of Women Age 24 and Under.

OBJECTIVES: In 2012, Ontario's cervical cancer screening program changed the age of initial screening from 18 years of age to 21 and identified women aged 21-24 years as a special population whose cervical squamous intraepithelial lesions should be managed conservatively. In order to provide insight into these changes, we sought to examine patient, provider, and clinical characteristics of cervical cancer screening and colposcopy care in women aged 12-24 years. METHODS: We conducted a retrospective population-based cohort study of all women in Ontario, aged 12-24 years, who underwent a Pap test between 2012 and 2014. Variables measured included, patient age, cytologic result of the index Pap test; colposcopy and definitive treatment within 1.5 years of the index Pap test; and carcinoma in situ (CIS) and invasive cervical cancer (ICC) 1.5 years after the index Pap test. Descriptive statistics were calculated for variables, and incidence rates per 100 000 women screened were calculated for CIS and ICC. RESULTS: A total of 270 391 index Pap tests were performed. The majority of patients were between 18 and 24 years of age (12-17 y: 5.5%; 18-20 y: 24.3%; 21-24 y: 70.1%). Overall, 87.0% of Pap tests were normal, 6.9% of women underwent subsequent colposcopy, and 1.1% received any treatment. Of women with a high-grade result, 86.6% (n = 1279) underwent colposcopy and 42.8% (n=632) received any treatment. Of women with a low-grade result, 42.3% (n = 13 856) underwent colposcopy, and 6.0% (n = 1955) had any treatment. Age-standardized rates of CIS and ICC in were 161.5 and 1.0 per 100 000 women, respectively. CONCLUSIONS: Despite the change in the screening guidelines, women under the age of 21 continue to be screened. This study highlights the low risk of ICC in women under age 25 and lays groundwork for re-examining screening guidelines for women in this age group. Furthermore, colposcopy referrals for women with a low-grade result on an index Pap test, and treatment of women under 24 years of age continue to be high. Future work must address the over-utilization of population-based screening, as well as factors related to adherence to screening guidelines.

Performance Indicators for Colposcopy in Ontario.

OBJECTIVE: This study sought to evaluate the delivery of colposcopy assessments and treatments in Ontario from 2009 to 2017 according to specific performance measures, derived from guidelines on colposcopy use. METHODS: This population-based descriptive analysis included screen-eligible women ages 21 to 69 in Ontario who underwent cervical screening between 2009 and 2017. Performance measures that describe the quality of colposcopy services in the province were calculated. RESULTS: Five performance measures were used to assess the use of colposcopy in Ontario from 2009 to 2017. From 2013 to 2017, the percentage of women seen for colposcopy after a first diagnosis of atypical squamous cells of undetermined significance (ASCUS), without evidence of repeat cytology, remained stable, ranging from 5.9% to 6.3%. The median wait time to colposcopy for atypical glandular cells (AGC), atypical squamous cells (ASC-H), cannot rule out high-grade squamous intraepithelial lesions, and high-grade squamous intraepithelial lesions (HSIL), remained relatively stable from 2013 to 2017. In addition, the percentage of women with high-grade Pap test results who were seen in colposcopy within 6 months increased from 74.7% to 83.5%. The percentage of women who were not seen in follow-up within 12 months after treatment for cervical dysplasia remained stable, as did the percentage of women who discontinued colposcopy after three normal Pap test results following treatment for cervical dysplasia. CONCLUSION: This study developed five performance indicators and used them to assess the delivery of colposcopic services in Ontario from 2009 to 2017. Performance indicators have previously been used effectively in the field of colorectal cancer screening to identify strengths and weaknesses in the delivery of healthcare services. This had never previously been done in colposcopy.

Risk of Cervical Dysplasia After Colposcopy Care and Risk-Informed Return to Population-Based Screening: A Systematic Review.

This systematic review examined the risk of cervical dysplasia among women who have undergone a colposcopy episode of care to inform their return to population-based cervical screening. PubMed, Embase, and grey literature were searched between January 2000 and 2018. One reviewer screened citations against pre-defined eligibility criteria. A second reviewer verified 10% and 100% of exclusions at title and abstract and at full-text screening, respectively. One reviewer extracted data and assessed methodological quality of included articles; a second reviewer verified these in full. The primary outcome was incidence of cervical intraepithelial neoplasia grade 2 or greater (CIN2+) subsequent to initial colposcopy evaluation. Secondary outcomes included incidence of CIN2+ after negative follow-up test results and performance of follow-up strategies. Results were synthesized narratively. A total of 48 studies were included. The 1- to 5-year CIN2+ risks after colposcopy evaluation ranged from 2.4% to 16.5% among women treated for CIN2+ and from 0.7% to 16.8% among women untreated for CIN grade 1 or less (≤CIN1). Follow-up strategies included single or repeat cytology, human papillomavirus (HPV) testing, or combined HPV/cytology co-testing at various intervals. After negative follow-up test results, risk varied by follow-up strategy for both groups and by referral cytology severity for untreated women. Performance of follow-up strategies varied among treated women. Among untreated women, co-testing demonstrated greater sensitivity than cytology alone. In conclusion, women treated during colposcopy for CIN2+ and women with ≤CIN1 who were referred to colposcopy for low-grade cytology and who did not receive treatment may be able to return to population-based screening after negative co-testing results. Current evidence does not suggest that women untreated for ≤CIN1 who are referred for high-grade cytology be returned to screening at an average risk interval. The optimal strategy for colposcopy discharge needs ongoing evaluation as implementation of HPV testing evolves.

Risk of Recurrence After Treatment for Cervical Intraepithelial Neoplasia 3 and Adenocarcinoma In Situ of the Cervix: Recurrence of CIN 3 and AIS of Cervix.

OBJECTIVES: The aim of the study was to evaluate recurrence risk of cervical intraepithelial neoplasia (CIN) 3+ and adenocarcinoma in situ (AIS)+ in a large population cohort of women previously treated for CIN 3/AIS. METHODS: Merging administrative databases with information on health services utilization and jurisdictional cancer registry, we identified all women undergoing treatment for CIN 3 or AIS from 2006 to 2010. Recurrence rate 1-5 years after treatment was defined as a biopsy finding of CIN 3/AIS or retreatment (loop electrosurgical excision procedure [LEEP], laser, cone, hysterectomy). Logistic regression was used to determine odds of recurrence. RESULTS: A total of 15,177 women underwent treatment for CIN 3 (n = 14,668) and AIS (n = 509). The recurrence rate for 5 years was greater for AIS (9.0%) compared with CIN 3 (6.1%). In a multivariate analysis, increased risk of recurrence was shown for age older than 45 years (hazard ratio (HR) = 1.3, 95% CI = 1.1-1.6), AIS compared with CIN 3 (HR = 2.2, 95% CI = 1.5-3.5) first cytology after treatment showing high grade (HR = 12.4, 95% CI = 9.7-15.7), and no normal Pap smears after treatment (HR = 2.8, 95% CI = 2.2-3.7). There was no difference in recurrence risk with treatment type (cone vs LEEP: HR = 1.0, 95% CI = 0.8-1.2, and laser vs LEEP: HR = 1.1, 95% CI = 0.8-1.4) or number of procedures per year performed by physicians (<40 vs >40 procedures: HR = 1.1, 95% CI = 0.9-1.3). CONCLUSIONS: Recurrence risk of CIN 3 and AIS is related to age, histology, and posttreatment cytology, which should assist with discharge planning from colposcopy. Definitive treatment with hysterectomy should be considered in women older than 45 years with additional risk factors for recurrence.