Safety of vaginal surgery for early-stage cervical cancer: A retrospective multicenter cohort study.

OBJECTIVE: Abdominal Radical hysterectomy (ARH) with pelvic lymph node assessment is considered the standard treatment for early-stage cervical cancer. Accepted routes have previously included laparoscopic or robotic approaches (LRH). Laparoscopy-assisted vaginal or vaginal radical hysterectomy (LVRH) are performed in some centers. The objective of this study is to compare surgical and oncological outcomes of LVRH, to laparoscopic and abdominal approaches. DESIGN PATIENTS SETTING: A retrospective multicenter analysis of consecutive cervical cancer cases who underwent a radical hysterectomy between 2007 and 2017 in eleven regional cancer centers across Canada. MEASUREMENTS: A comparison of patients stratified by surgical technique was undertaken. T-test, Wilcoxon rank-sum and chi-square were used to compare patient characteristics. Log-rank tests and Cox proportional hazards models were employed to compare recurrence and survival across surgical groups. MAIN RESULTS: A total of 1071 patients with cervical cancer stage IA1 with lymphovascular invasion to stage IIIC (FIGO 2018) <4 cm were identified. Postoperative complication rate was lowest for women undergoing LVRH (9.1 %, vs 18.3 % and 22.1 % for minimally invasive and open respectively). During follow up, 114 women recurred, and 70 women died. 5-year recurrence-free survival was 85.4 % for LRH, 89.4 % for ARH and 92.2 % for LVRH. LVRH was not found to be associated with a higher risk of recurrence or death than ARH on multivariable analysis (aHR for recurrence 0.62, CI 0.21-1.77; aHR for death 0.63, CI 0.14-2.77) CONCLUSION: In this retrospective study, vaginal or laparoscopy-assisted vaginal radical hysterectomy for cervical cancer was associated with favorable perioperative and oncological outcomes.

A multilingual sexual and reproductive health animation: a novel educational tool for newcomer patients.

Newcomer populations face many barriers accessing healthcare, including language barriers. Language-concordant care has been shown to enhance equity and optimize health outcomes for underserved populations. This paper describes a sexual and reproductive health (SRH) animation for newcomer populations. The animation was created collaboratively by the Department of Obstetrics and Gynaecology Global Health Unit, the Halifax Newcomer Health Clinic, and student volunteers. Integrating this animation into other healthcare settings may help improve inclusion, trust, and patient-centred care for newcomer patients. Institutions may also consider creating further SRH animations based on the needs of the patients they serve.

Les nouveaux arrivants sont confrontés à de nombreux obstacles dans l'accès aux soins de santé, notamment des barrières linguistiques. Il a été démontré qu'une concordance linguistique au cours des soins améliorent l'équité et les résultats en matière de santé pour les populations mal desservies. Cet article décrit une animation sur la santé sexuelle et reproductive pour les nouveau arrivants. Cette animation a été conçue en collaboration par l'unité de santé mondiale du département d'obstétrique et de gynécologie, la clinique de santé pour les nouveaux arrivants de Halifax et des étudiants bénévoles. L'intégration de cette animation dans d'autres contextes de soins peut contribuer à améliorer l'inclusion, la confiance et les soins centrés sur le patient pour les nouveaux arrivants. Les établissements peuvent également envisager de concevoir d'autres animations sur la santé sexuelle et reproductive en fonction des besoins de la population qu'ils desservent.

2023 Canadian Colposcopy Guideline: A Risk-Based Approach to Management and Surveillance of Cervical Dysplasia.

This guideline provides evidence-based guidance on the risk-based management of cervical dysplasia in the colposcopy setting in the context of primary HPV-based screening and HPV testing in colposcopy. Colposcopy management of special populations is also discussed. The guideline was developed by a working group in collaboration with the Gynecologic Oncology Society of Canada (GOC), Society of Colposcopists of Canada (SCC) and the Canadian Partnership Against Cancer (CPAC). The literature informing these guidelines was obtained through a systematic review of the relevant literature via a multi-step search process led by information specialists. The literature was reviewed up to June 2021 with manual searches of relevant national guidelines and more recent publications. Quality of the evidence and strength of recommendations was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework. The intended users of this guideline include gynecologists, colposcopists, screening programs and healthcare facilities. Implementation of the recommendations is intended to promote equitable and standardized care for all people undergoing colposcopy in Canada. The risk-based approach aims to improve personalized care and reduce over-/under-treatment in colposcopy.

Surgical margin status in relation to surgical approach in the management of early-stage cervical Cancer: A Canadian cervical Cancer collaborative (4C) study.

OBJECTIVE: Surgical margin status in women undergoing surgery for early-stage cervical cancer is an important prognostic factor. We sought to determine whether close (<3 mm) and positive surgical margins are associated with surgical approach and survival. METHODS: This is a national retrospective cohort study of cervical cancer patients treated with radical hysterectomy. Patients with stage IA1/LVSI-Ib2(FIGO 2018) with lesions up to 4 cm at 11 Canadian institutions from 2007 to 2019 were included. Surgical approach included robotic/laparoscopic (LRH), abdominal (ARH) or combined laparoscopic-assisted vaginal/vaginal (LVRH) radical hysterectomy. Recurrence free survival(RFS) and overall survival (OS) were estimated using Kaplan-Meier analysis. Chi-square and log-rank tests were used to compare groups. RESULTS: 956 patients met inclusion criteria. Surgical margins were as follows: negative (87.0%), positive (0.4%) or close <3 mm (6.8%), missing (5.8%). Most patients had squamous histology (46.9%); 34.6% had adenocarcinomas and 11.3% adenosquamous. Most were stage IB (75.1%) and 24.9% were IA. Mode of surgery included: LRH(51.8%), ARH (39.2%), LVRH (8.9%). Predictive factors for close/positive margins included stage, tumour diameter, vaginal involvement and parametrial extension. Surgical approach was not associated with margin status (p = 0.27). Close/positive margins were associated with a higher risk of death on univariate analysis (HR = non calculable for positive and HR = 1.83 for close margins, p = 0.017), but not significant for OS when adjusted for stage, histology, surgical approach and adjuvant treatment. There were 7 recurrences in patients with close margins (10.3%, p = 0.25). 71.5% with positive/close margins received adjuvant treatment. In addition, MIS was associated with a higher risk of death (OR = 2.39, p = 0.029). CONCLUSION: Surgical approach was not associated to close or positive margins. Close surgical margins were associated with a higher risk of death. MIS was associated with worse survival, suggesting that margin status may not be the driver of worse survival in these cases.

Oncologic Outcomes of Surgically Treated Cervical Cancer with No Residual Disease on Hysterectomy Specimen: A 4C (Canadian Cervical Cancer Collaborative) Working Group Study.

Minimally invasive surgery for the treatment of macroscopic cervical cancer leads to worse oncologic outcomes than with open surgery. Preoperative conization may mitigate the risk of surgical approach. Our objective was to describe the oncologic outcomes in cases of cervical cancer initially treated with conization, and subsequently found to have no residual cervical cancer after hysterectomy performed via open and minimally invasive approaches. This was a retrospective cohort study of surgically treated cervical cancer at 11 Canadian institutions from 2007 to 2017. Cases initially treated with cervical conization and subsequent hysterectomy, with no residual disease on hysterectomy specimen were included. They were subdivided according to minimally invasive (laparoscopic/robotic (MIS) or laparoscopically assisted vaginal/vaginal hysterectomy (LVH)), or abdominal (AH). Recurrence free survival (RFS) and overall survival (OS) were estimated using Kaplan-Meier analysis. Chi-square and log-rank tests were used to compare between cohorts. Within the total cohort, 238/1696 (14%) had no residual disease on hysterectomy specimen (122 MIS, 103 AH, and 13 VLH). The majority of cases in the cohort were FIGO 2018 stage IB1 (43.7%) and underwent a radical hysterectomy (81.9%). There was no statistical difference between stage, histology, and radical vs simple hysterectomy between the abdominal and minimally invasive groups. There were no significant differences in RFS (5-year: MIS/LVH 97.7%, AH 95.8%, p = 0.23) or OS (5-year: MIS/VLH 98.9%, AH 97.4%, p = 0.10), although event-rates were low. There were only two recurrences. In this large study including only patients with no residual cervical cancer on hysterectomy specimen, no significant differences in survival were seen by surgical approach. This may be due to the small number of events or due to no actual difference between the groups. Further studies are warranted.

Comparison of outcomes between abdominal, minimally invasive and combined vaginal-laparoscopic hysterectomy in patients with stage IAI/IA2 cervical cancer: 4C (Canadian Cervical Cancer Collaborative) study.

OBJECTIVE: Although minimally invasive hysterectomy (MIS-H) has been associated with worse survival compared to abdominal hysterectomy (AH) for cervical cancer, only 8% of patients in the LACC trial had microinvasive disease (Stage IA1/IA2). We sought to determine differences in outcome among patients undergoing MIS-H, AH or combined vaginal-laparoscopic hysterectomy (CVLH) for microinvasive cervical cancer. METHODS: A retrospective cohort study of all patients undergoing hysterectomy (radical and non radical) for FIGO 2018, microinvasive cervical cancer across 10 Canadian centers between 2007 and 2019 was performed. Recurrence free survival (RFS) was estimated using Kaplan Meier Survival analysis. Chi-square and log-rank tests were used to compare outcomes. RESULTS: 423 patients with microinvasive cervical cancer were included; 259 (61.2%) Stage IA1 (22/8.5% with LVSI) and 164(38.8%) IA2. The median age was 44 years (range 24-81). The most frequent histology was squamous (59.4%). Surgical approach was: 50.1% MIS-H (robotic or laparoscopic), 35.0% AH and 14.9% CVLH. Overall, 70.9% underwent radical hysterectomy and 76.5% had pelvic lymph node assessment. There were 16 recurrences (MIS-H:4, AH:9, CVLH: 3). No significant difference in 5-year RFS was found (96.7% MIS-H, 93.7% AH, 90.0% CVLH, p = 0.34). In a sub-analysis of patients with IA1 LVSI+/IA2(n = 186), survival results were similar. Further, there was no significant difference in peri-operative complications (p = 0.19). Patients undergoing MIS-H had a shorter median length of stay(0 days vs 3 (AH) vs. 1.5 (CVLH), p < 0.001), but had more ER visits (16.0% vs 3.6% (AH), 3.5% (CVLH), p = 0.036). CONCLUSION: In this cohort, including only patients with microinvasive cervical cancer, no difference in recurrence was found by surgical approach. This may be due to the low rate of recurrence making differences hard to detect or due to a true lack of difference. Hence, this patient population may benefit from MIS without compromising oncologic outcomes.

Incidence of anogenital warts after the introduction of the quadrivalent HPV vaccine program in Manitoba, Canada.

BACKGROUND: The incidence of anogenital warts (AGW) decreased after the introduction of the quadrivalent human papillomavirus (qHPV) vaccine in multiple jurisdictions. We studied how comparing AGW incidence rates with different outcomes affects the interpretation of the qHPV vaccination program. To do this, we replicated multiple study designs within a single jurisdiction (Manitoba). METHODS: We measured the incidence rates of AGW, AGW-related prescriptions, chlamydia, and gonorrhea (the latter two as sham outcomes) between 2001 and 2017 using several clinical and administrative health databases from Manitoba. We then used incidence rate ratios (IRRs) to compare, for each outcome, the rate for the 1997-1998 birth cohort (the first cohorts eligible for the publicly funded qHPV vaccination program) and the older 1995-1996 birth cohort. RESULTS: AGW incidence in Manitoba dropped 72% (95% confidence interval 54-83%) among 16-18 year-old girls and 51% (14-72%) among boys after the introduction of the female-only qHPV vaccination program. Trends in AGW-related prescriptions were different from trends in AGW diagnoses as these prescriptions peaked shortly after the introduction of the publicly funded qHPV vaccine program. Chlamydia and gonorrhea incidence rates also decreased 12% (5-18%) and 16% (-1-30%), respectively, for 16-18 year-old girls. CONCLUSIONS: The publicly funded school-based qHPV vaccine program reduced AGW incidence in Manitoba by three-quarters in young females. AGW-related prescriptions are a poor proxy for medically attended AGW after the introduction of the publicly funded qHPV vaccination program. Different sexual habits in adolescents are, at most, responsible for a small portion of the reduction in AGW incidence.

Impact of surgical approach on oncologic outcomes in women undergoing radical hysterectomy for cervical cancer.

BACKGROUND: Recent studies demonstrating shorter survival among cervical cancer patients undergoing minimally invasive versus open radical hysterectomy could not account for surgeon volume and require confirmation in other jurisdictions with larger sample sizes, longer follow-up, and data on disease recurrence. OBJECTIVE: To determine if surgical approach is associated with oncologic outcomes in cervical cancer patients undergoing minimally invasive or open radical hysterectomy, while accounting for mechanistic factors including surgeon volume. STUDY DESIGN: We performed a population-based retrospective cohort study of cervical cancer patients undergoing primary radical hysterectomy by a gynecologic oncologist from 2006 to 2017 in Ontario, Canada. A multivariable marginal Cox proportional hazards model and cause-specific hazards model were used to evaluate the association of surgical approach with all-cause death and recurrence respectively, clustering at the surgeon level. We tested for interactions between surgical approach and either pathologic stage or surgeon volume. RESULTS: We identified 958 patients (minimally invasive 475; open 483) with mean age 45.9 and a median follow-up of 6 years. Of minimally invasive procedures, 89.6% were performed laparoscopically and 10.4% robotically. The unadjusted 5-year cumulative incidences of all-cause death (minimally invasive 12.5%; open 5.4%), cervical cancer death (minimally invasive 9.3%; open 3.3%), and recurrence (minimally invasive 16.2%; open 8.4%) were significantly increased for minimally invasive radical hysterectomy in patients with stage IB disease, but not the cohort overall. After adjusting for patient factors and surgeon volume, minimally invasive radical hysterectomy was associated with increased rates of death (hazard ratio [HR], 2.20; 95% confidence interval [CI], 1.15-4.19) and recurrence (HR, 1.97; 95% CI, 1.10-3.50) compared to open radical hysterectomy in patients with stage IB disease (n = 534), but not IA disease (n = 244; HR, 0.73; 95% CI, 0.13-4.01; HR, 0.34; 95% CI, 0.10-1.10). CONCLUSION: Minimally invasive radical hysterectomy is associated with increased rates of death and recurrence in patients with stage IB cervical cancer even after controlling for surgeon volume; open radical hysterectomy should be the recommended approach in this population. Although there may be a subset of patients with microscopic early-stage disease for whom minimally invasive radical hysterectomy remains safe, additional studies are required.

Rates over time and regional variation of radical minimally invasive surgery for cervical cancer: A population based study.

OBJECTIVE: Determine rates of radical minimally invasive surgery (MIS) for cervix cancer in Ontario, and whether these rates varied over time and by region. Assess whether changes in the use of MIS impacted length of hospital stay and readmissions. METHODS: Retrospective population-based cohort study of women undergoing radical surgery for cervical cancer between 2002 and 2015. Radical MIS versus laparotomy were compared. Trends in rate of MIS over time, length of hospital stay, and readmission within 30 days were determined. Multivariate logistic regression was used to determine factors associated with MIS approach. RESULTS: 805 women underwent radical abdominal surgery versus 538 radical minimally invasive surgery. Radical MIS increased over the study period, from 17.7% in 2002 to 61.5% in 2015. The most significant predictor of MIS approach was hospital site, with a 14-fold difference in sites with highest and lowest uptake of MIS. Mean length of hospital stay was significantly shorter after radical MIS compared to radical abdominal surgery (1.1 v. 4.2 days). Hospital readmission within 30 days was reduced over the study period for MIS but remained stable following abdominal surgery. CONCLUSIONS: Although rates of radical MIS increased in Ontario over the time period studied, this seems to have been driven by a few high volume centres. Cervical cancer is rare and it takes time to develop the skills to carry out the procedure effectively. Abandonment of minimally invasive radical hysterectomy may have a significant impact on surgical training and subsequent proficiency in the skills unique to this procedure.

Early Evidence of the Effectiveness of the Human Papillomavirus Vaccination Program Against Anogenital Warts in Manitoba, Canada: A Registry Cohort Study.

BACKGROUND: We assessed the effectiveness of the quadrivalent human papillomavirus vaccine (qHPV) vaccination program in Manitoba, Canada, in reducing incident anogenital warts (AGWs) and to what extent effectiveness depends on age at vaccination and number of doses. METHODS: Female participants 9 years or older who received the qHPV in Manitoba between September 2006 and March 2013 (n = 31,464) through the publicly funded school-based program and a high-risk catch-up program were included. They were matched on age and area of residence to unvaccinated female participants. Information on incident AGWs was obtained from provincial administrative databases using validated algorithms. Using stratified Cox regression models, we estimate hazard ratios (HRs) for the association between qHPV and AGWs. RESULTS: For female participants vaccinated at age 18 years or younger, receipt of qHPV was associated with a 40% reduction in AGW risk (HR, 0.6; 95% confidence interval [CI], 0.4-0.8). Further adjustment for socioeconomic and medical history did not alter this estimate. For women vaccinated at age 19 years or older, we saw an increase in AGW incidence, especially among those who were sexually active (HR, 2.8; 95% CI, 2.1-3.7). Among female participants vaccinated at age 18 years or younger, risk of AGWs was lowest among those who received 3 doses, corresponding to a vaccine effectiveness of 56% (95% CI, 30%-70%). For women vaccinated at older age, risk of AGWs remained increased regardless of the number of doses. CONCLUSIONS: Women vaccinated at an older (≥19 years) age may be less protected against AGWs, particularly if sexually active before vaccine administration. Further efforts should be targeted at increasing vaccine uptake among preadolescents before the initiation of sexual activity.

BRCA Mutation Status Is Not Associated With Increased Hematologic Toxicity Among Patients Undergoing Platinum-Based Chemotherapy for Ovarian Cancer.

OBJECTIVE: Women with an inherited BRCA1 or BRCA2 mutation may have an impaired ability to repair chemotherapy-induced damage as a result of a state of haploinsufficiency and may experience greater treatment-related toxicity. The objective of this study was to compare the hematologic adverse effect profiles associated with platinum-based chemotherapy in ovarian cancer patients with and without germline BRCA mutations. METHODS: We conducted a retrospective analysis of patients treated for high-grade serous ovarian cancer at Princess Margaret Cancer Center, Toronto, Ontario between January 2000 and December 2015. We included only women with known BRCA mutation status and who received first-line platinum-based chemotherapy. We compared 3 primary measures of myelosuppression (ie, hemoglobin levels, platelet counts, and neutrophil counts) before each cycle of chemotherapy in patients with and without a BRCA mutation. RESULTS: We included 130 BRCA mutation carriers and 302 noncarriers who met the eligibility criteria. There were no significant differences in baseline hemoglobin levels, neutrophil counts, or platelet counts between the groups (P ≥ 0.31). We found no significant difference in 3 measures of hematologic toxicity (ie, neutropenia, anemia, or thrombocytopenia) based on BRCA mutation status across all chemotherapy cycles (P ≥ 0.06). Although BRCA mutation carriers were more likely to experience an absolute neutrophil count below 1.0 × 10/L than noncarriers (P = 0.02), this did not translate to an increased frequency of dose reduction or dose delay. DISCUSSION: Among women with ovarian cancer, hematologic toxicity does not appear to be more frequent in BRCA mutation carriers than in noncarriers. This is reassuring for clinicians treating ovarian cancer patients with respect to dosing regimens. These findings do not support the hypothesis that a haploinsufficiency phenotype exists with respect to the repair of chemotherapy-induced double-strand DNA breaks in this high-risk population.

Early Cervical Cancer: Current Dilemmas of Staging and Surgery.

PURPOSE OF REVIEW: Advances in cervical cancer screening and treatment have resulted in high cure rates in developed countries for early-stage disease. Current research focuses on minimizing morbidity and maximizing quality of life. RECENT FINDINGS: Imaging has been disappointing in identifying small volume metastases. Sentinel lymph node biopsy represents a significant advantage with high sensitivity, low false negative rates, reduced morbidity, and equivalent survival in recent studies compared to pelvic lymphadenectomy. Non-radical surgical options are currently being investigated for early cervical cancer in a number of large prospective studies in patients at low risk for metastases. Evidence suggests that sentinel lymph node biopsy and non-radical surgery are safe approaches for the staging and management of early cervical cancer in appropriately selected patients with the potential to significantly reduce treatment-related morbidity.

Fertility-sparing management in cervical cancer: balancing oncologic outcomes with reproductive success.

BACKGROUND: Cervical cancer is the fourth most common cancer among women worldwide, many of who are still within their reproductive lifespan. Advances in screening and treatment have increased the 5-year survival for early stage disease to over 90 % in developed countries. The focus is now shifting to reducing morbidity and improving fertility outcomes for cervical cancer patients. Radical trachelectomy with lymph node assessment became the standard of care for selected women with lesions <2 cm who desire fertility preservation. However, several questions still remain regarding the degree of surgical radicality required for tumors <2 cm, and fertility-sparing options for women with early-stage disesase ≥2 cm, and those with more advanced disease. Here, we compile a narrative review of the evidence for oncologic and pregnancy outcomes following radical trachelectomy, non-radical fertility-sparing surgery, and the use of neoadjuvant chemotherapy prior to surgery for larger lesions. We also review the literature for assisted reproductive technologies in women with more advanced disease. FINDINGS: Available literature suggests that the crude recurrence and mortality rates after radical trachelectomy are <5 and <2 %, respectively (approx. 11 and 4 % for tumors ≥ 2 cm). Among 1238 patients who underwent fertility-sparing surgery for early cervical cancer there were 469 pregnancies with a 67 % live birth rate. Among 134 cases with lesions ≥ 2 cm, there were ten conceptions with a live birth rate of 70 %. Outcomes after non-radical surgery (simple trachelectomy or cervical conization) are similar, although only applicable among a highly selected patient population. For patients ineligible for fertility-preserving surgery or who require adjuvant radiation therapy, current options include ovarian transposition and cryopreservation of oocytes or embryos but other techniques are under investigation. CONCLUSION: Today, many cervical cancer survivors have successful pregnancies. For those with early-stage disease, minimally invasive and fertility sparing techniques have resulted in improved obstetrical outcomes without compromising oncologic safety. Results from three ongoing trials on non-radical surgery for low-risk tumors <2 cm will further inform the need for radical surgery in such patients. For those in whom natural childbearing is unachievable, advances in assisted reproductive technologies provide reproductive options. Despite our advances, the effects of cervical cancer survivorship on quality of life are not fully elucidated.

Evolutionary dynamics of the mS952 intron: a novel mitochondrial group II intron encoding a LAGLIDADG homing endonuclease gene.

Examination of the mitochondrial small subunit ribosomal RNA (rns) gene of five species of the fungal genus Leptographium revealed that the gene has been invaded at least once at position 952 by a group II intron encoding a LAGLIDADG homing endonuclease gene. Phylogenetic analyses of the intron and homing endonuclease sequences indicated that each element in Leptographium species forms a single clade and is closely related to the group II intron/homing endonuclease gene composite element previously reported at position 952 of the mitochondrial rns gene of Cordyceps species and of Cryphonectria parasitica. The results of an intron survey of the mt rns gene of Leptographium species superimposed onto the phylogenetic analysis of the host organisms suggest that the composite element was transmitted vertically in Leptographium lundbergii. However, its stochastic distribution among strains of L. wingfieldii, L. terebrantis, and L. truncatum suggests that it has been horizontally transmitted by lateral gene transfer among these species, although the random presence of the intron may reflect multiple random loss events. A model is proposed describing the initial invasion of the group II intron in the rns gene of L. lundbergii by a LAGLIDADG homing endonuclease gene and subsequent evolution of this gene to recognize a novel DNA target site, which may now promote the mobility of the intron and homing endonuclease gene as a composite element.