Reproductive outcomes after fertility-sparing surgery for cervical cancer - results of the multicenter FERTISS study.

INTRODUCTION: Fertility-sparing treatment (FST) for patients with cervical cancer intends to achieve oncologic outcomes comparable to those after radical treatment while maximizing reproductive outcomes, including the ability to conceive and minimizing the risk of prematurity. METHODOLOGY: International multicentre retrospective FERTISS study focused on patients treated with FST analysed timing of FST relative to pregnancy, conception attempts and methods, abortion rates, prophylactic procedures reducing the risk of severe prematurity, pregnancy duration, and delivery mode. RESULTS: Of the 733 patients treated at 44 centres in 13 countries, 49.7% attempted to conceive during median follow-up of 72 months and 22.6% (166/733) patients achieved a successful pregnancy. Success rate was significantly higher after non-radical surgery (63.2%; 122/193) compared to radical trachelectomy (25.7%; 44/171, p < 0.001). Available perinatological data shows that 89.5% (111/124) of the patients became pregnant naturally. There was no significant difference in the abortion rate in the first pregnancy nor delivery success rates between non-radical and radical procedures patients. Preterm delivery (<38 weeks gestation) occurred more frequently after radical than non-radical procedures (76.5% vs. 57.7%, p = 0.15). Almost all patients (97.3%; 73/75) who underwent regular ultrasound cervicometry in pregnancy with subsequent prophylactic procedures delivered a live fetus, compared to 30.6% (15/49) women without such management, p < 0.001. CONCLUSION: Patients who underwent non-radical surgery had significantly higher pregnancy rates. Most pregnancies resulted in a viable fetus, but radical trachelectomy led to a higher rate of preterm births in the severe prematurity range. Half of the patients did not attempt pregnancy after FST.

Follow-up of women with cervical adenocarcinoma in situ treated by conization: A single centre clinical experience.

OBJECTIVE: Hysterectomy has been the historical gold standard final step in the treatment algorithm of adenocarcinoma in situ (AIS) recommended by most North American colposcopy guidelines. AIS disproportionately affects young childbearing age women, therefore a fertility sparing treatment option is desirable. Our study examines the impact of conservative treatment of AIS with conization followed by serial surveillance. METHODS: A retrospective chart review was completed of patients treated for AIS from 2006 to 2020. Charts were identified by pathologic diagnosis of AIS on cervical and uterine specimens. Charts were excluded if AIS was not treated with conization, if AIS was not confirmed on initial conization specimen, or if invasive disease was found at initial conization. RESULTS: 121 patient charts were analyzed. Median age of patients at first conization and hysterectomy was 34.8 and 40.9, respectively. First conization was by Cold Knife Cone in 58% of patients, and by Loop Electrosurgical Excisional Procedure in 42% of patients. Median follow-up period in our study was 609 days. 5% of patients had recurrence, with only one patient who recurred as cancer. One case of recurrence had a positive initial conization margin. Median time to recurrence was 700 days. 47% of patients underwent eventual hysterectomy. Residual AIS was found in 23% of hysterectomy specimens. Adenocarcinoma was diagnosed on hysterectomy specimen in four patients. CONCLUSION: Our study demonstrates the oncologic safety of treating AIS with conization and serial surveillance. Routine hysterectomy completed as a part of the AIS treatment algorithm, as in current clinical guidelines, is unnecessary.

A simplified modification of the Sturmdorf suture.

The Sturmdorf type sutures are traditionally used for obtaining hemostasis after a cold knife conization. In this article and accompanying video, we provided a simplified modification of the Sturmdorf suture to further reduce the risk of postoperative bleeding and cervical stenosis. Our modified Sturmdorf suture is essentially a large horizontal figure-of-eight suture, with simultaneous small bites on the mucosa of the anterior and posterior lips drawing the cervical mucosa to cover the denuded cervical stump. The advantages of this modification are: (1) The surgery is simple, accomplished with only one suture; (2) excellent hemostasis is achieved by incorporating the cervical branch of the descending rami of the uterine artery lateral to the cervix in the suture loop; (3) the single-suture technique provides more appropriate tension on the cervix when tying the knot and pulls the cervical mucosa towards the cervical canal from six symmetrical directions, evenly distributed tension helps restore the preferable cylindrical shape of the cervical stump; and (4) the intersection point of the figure-of-eight suture is located in the cervical canal, where the tissue undergoes minimal deformation when the suture loop is tightened, therefore stenosis of the uterine cervix is rare.

Diagnostic cervical excision in patients with HPV positivity, cytological abnormalities- and preoperative cervical stenosis.

AIM: There is currently no protocol for classifying patients with HPV persistence and preoperative stenosis of the cervical canal. This has a significant impact on cytology results, colposcopy results and the possibility of obtaining reliable cervical histology outcomes. Our analysis clearly shows that colposcopy and cytology underestimate the histological results in patients with limited visibility due to the presence of a type 3 transformation zone (TZ). Our analysis revealed a significant discrepancy between the colposcopy and cytology results and the histological outcomes. Insufficient colposcopy led to the underdiagnosis of dysplastic lesions in patients with a type 3 TZ and cervical stenosis. In the case of repeated cytological abnormalities and inadequate colposcopy examination, it is crucial to perform a diagnostic conization to exclude high-grade dysplastic changes and cervical carcinoma. METHODS: We conducted a retrospective analysis of 1,021 conizations performed in tertiary care hospital in Wolfsburg, Germany between 2014 and 2020. Of these surgical procedures, 89 were diagnostic conizations. In our analysis, we defined diagnostic conization as a procedure performed when there is HPV persistence and repeated cytologic abnormalities in combination with a type 3 TZ, and when it is not possible to retrieve a relevant cervical histology sample. RESULTS: In this period, 8.7% of all conizations were diagnostic excisions. We found histological abnormalities in 48 of 89 patients (53.9%). The histological examination of the excised cone revealed high-grade cervical intraepithelial neoplasia (CIN/HSIL) in 9 patients (10.1%) and CIN 2+ (HSIL) in 23 out of the 89 patients (25.8%). Two cases of early-stage cervical carcinoma (FIGO IA1 and FIGO IA2) were confirmed (2.3%). CONCLUSION: Patients with cervical stenosis, high-risk HPV persistence and repeated cytological abnormalities are at high risk of undetected high-grade cervical dysplasia. Histologic confirmation must be ensured in this patient consultation and this can be achieved by performing diagnostic excisions.

Expanding management strategies for cervical precancerous lesions in resource-limited settings: insights from a training center in a district hospital in Ghana.

BACKGROUND: Cervical cancer continues to disproportionately burden women in low/middle-income countries like Ghana. We examined treatment patterns and histopathological outcomes among women screened using visual inspection with acetic acid (VIA) and/or mobile colposcopy who subsequently underwent thermal ablation, large loop excision of the transformation zone (LLETZ), or cold knife conization at the Cervical Cancer Prevention and Training Centre, Battor. We also assessed the prevalence of cervical intraepithelial neoplasia 2+ (CIN2+) or micro-invasive disease and their associated factors for women who underwent excisional treatments. The treatment choices for cervical precancerous lesions suitable for resource-limited settings have also been described from the perspective of a center that manages a heterogenous population. METHODS: We conducted an analysis of secondary data collected between June 2016 and June 2023 among women with positive findings on VIA or mobile colposcopy who subsequently underwent thermal ablation or large loop excision of the transformation zone (LLETZ). The prevalence of histopathology outcomes, including no dysplasia, CIN1 - 3, and micro-invasive disease, were estimated with 95% confidence intervals (CIs). Factors associated with histopathological findings were modeled using multinomial logistic regression. RESULTS: For the study period, 14 (10.6%) of the total 132 participants underwent cervical lesion treatment at outreach locations, all via thermal ablation. The remaining 118 (89.4%) were treated at the Catholic Hospital, Battor using LLETZ (n = 66, 55.9%), thermal ablation (n = 51, 43.2%), and cold knife conization (n = 1, 0.9%). Among 65 women with histopathology reports, the most frequent histopathological finding was no dysplasia (47.7%; 95% CI, 35.1 - 60.5), followed by CIN2 and CIN3 (20.0%; 95% CI, 11.1 - 31.8 each), CIN1 (7.7%; 95% CI, 2.5 - 17.0) and micro-invasion (4.6%; 95% CI, 1.0 - 12.9). Those with micro-invasive disease were significantly older than those with CIN1, CIN2, and CIN3 (p = 0.036, 0.022, 0.009, respectively), but not significantly older than those who showed no dysplasia (p = 0.088). For each unit increase in age, the likelihood of CIN3 was relatively significantly reduced compared to no dysplasia (crude relative risk ratio [RRR] = 0.93; 95% CI, 0.86 - 0.99). This association was neither observed with the remaining histopathological groups nor for parity and persisted after controlling for parity (adjusted RRR = 0.92; 95% CI, 0.85 - 0.99; p = 0.025). CONCLUSION: This paper largely demonstrates treatment options available to women and practitioners in LMICs. The high combined prevalence of high-grade precancerous lesions and micro-invasive disease underscores the need to increase cervical cancer awareness that would enhance screening attendance and hasten efforts at moving from opportunistic to organized screening in Ghana. This will enhance early cervical lesion detection and treatment, while simultaneously re-evaluating and cutting down on unnecessary treatment.

Radical Hysterectomy With Preoperative Conization in Early-Stage Cervical Cancer: A Systematic Review and Pairwise and Network Meta-Analysis.

OBJECTIVE: The investigation of the role of preoperative conization in cervical cancer aiming to explore its potential clinical significance. DATA SOURCES: Cochrane Library, Embase, PubMed, and Web of Science, up to April 28, 2023. METHODS OF STUDY SELECTION: (1) Observational cohort studies, (2) studies comparing radical hysterectomy with preoperative conization (CO) vs radical hysterectomy without preoperative conization (NCO) in patients with early-stage cervical cancer, and (3) studies comparing disease-free survival outcomes. TABULATION, INTEGRATION, AND RESULTS: Two reviewers independently extracted the data and assessed the quality of the studies. The meta-analysis used combined hazard ratios along with their corresponding 95% confidence intervals to compare CO and NCO. We conducted a Bayesian network meta-analysis using Markov chain Monte Carlo methods to compare minimally invasive CO, open CO, minimally invasive NCO, and open NCO. Our study included 15 retrospective trials, 10 of which were used to traditional pairwise meta-analysis and 8 for network meta-analysis. The NCO group exhibited a notably higher probability of cancer recurrence than the CO group (hazard ratio, 0.52; 95% confidence interval, 0.41-0.65). In the network meta-analysis, minimally invasive NCO showed the worst survival outcome. CONCLUSION: Preoperative conization seems to be a protective factor in decreasing recurrence risk, assisting clinicians in predicting survival outcomes for patients with early-stage cervical cancer. It may potentially aid in selecting suitable candidates for minimally invasive surgery in clinical practice.

Association between p16/Ki-67 dual stain cytology results prior to and 6 months after LLETZ treatment for CIN and the follow-up regimen three years after treatment: a retrospective cohort study.

OBJECTIVE: Investigate the association between p16/Ki-67 dual stain cytology test (DST) results, obtained prior to- and 6 months after LLETZ surgery for treatment of CIN, and the follow-up regimen three years after treatment. METHODS: Secondary analysis of a prospective cohort study. Cervical cytology samples were obtained just prior to- and 6 months after LLETZ and underwent conventional liquid-based cytology (LBC) and p16/Ki-67 dual staining, as well as high-risk HPV genotyping. Clinical management after the LLETZ was according to Belgian national guidelines, with clinicians being blinded to DST results at both time points. Case records were reviewed in 01/2023 to document the follow-up regimen on average three years afterwards: women had either been advised to return to routine screening (i.e., three-annual LBC testing according to the Belgian guideline at that time), or were still subject to more frequent posttreatment surveillance (i.e., more frequent visits because of persistent hrHPV infection or absence of cytological regression). RESULTS: The follow-up regimen was recorded in 79/110 women originally recruited (72%). The need for continued intense posttreatment surveillance was associated with hrHPV infection 6 months after treatment (79.3% vs. 18.0%, p < 0.001), a positive DST result at baseline and follow-up (41.4% vs. 84.0%, p < 0.001-55.2% vs. 16.0%, p < 0.001), and persistent cytological anomalies at 6 months (at an ASCUS or worse threshold, 37.9% vs. 16.0%, p = 0.028). In multivariable logistic regression analysis, a positive DST at baseline (aOR 20.1, 95%CI 2.03-199.1) was independently associated with the need for intense post-treatment surveillance multiple years after treatment. CONCLUSION: This exploratory study suggests a possible role of dual-stain cytology in predicting treatment outcome multiple years after LLETZ surgery.

Endocervical crypt involvement by high-grade cervical intraepithelial neoplasia and its association with high-grade histopathological recurrence after cervical excision in women with negative excision margins: a systematic review and meta-analysis.

BACKGROUND: There is a growing body of evidence suggesting that endocervical crypt involvement by high-grade cervical intraepithelial neoplasia (CIN) may represent a risk factor for disease recurrence after cervical treatment. OBJECTIVES: To provide a systematic review and meta-analysis on whether endocervical crypt involvement by high-grade CIN on the excised cervical specimen is associated with high-grade histopathological recurrence during the follow-up of women after cervical excisional treatment. SEARCH STRATEGY: We searched the Medline, Scopus, Central, and Clinical Trials.gov databases from inception till May 2023. SELECTION CRITERIA: Studies that reported on women with a single cervical treatment with any method of excision for CIN2 or CIN3 lesion, negative excision margins, and whose recurrence was defined histopathologically were included. DATA COLLECTION AND ANALYSIS: Two reviewers independently evaluated study eligibility. We used the fixed effects model for meta-analysis. MAIN RESULTS: There were 4 eligible studies included in the present systematic review that evaluated 1088 women treated with either large loop excision of the transformation zone (LLETZ) or with cold knife conization (CKC). We found no significant association of endocervical crypt involvement by CIN2-3 with high-grade histopathological recurrence at follow-up after cervical excision (OR 1.93; 95% CI 0.51-3.35). The subgroup analysis of women with LLETZ cervical excision showed again no significant association with high-grade histopathological recurrence at follow-up (OR 2.00; 95% CI 0.26-3.74). CONCLUSION: Endocervical crypt involvement by high-grade CIN does not seem to be a risk factor for high-grade histopathological recurrence after cervical excision with negative excision margins.

Cold Knife Versus Carbon Dioxide for the Treatment of Preinvasive Cervical Lesion.

Background and Objectives: Cervical cancer (CC) represents a significant health concern worldwide, particularly for younger women. Cold knife (CK) conization and carbon dioxide (CO2) laser conization are two techniques commonly used to remove pre-invasive lesions, offering a potential curative intent in cases of incidental diagnosis of CC. This study aimed to assess the clinical implications and pathological outcomes of CK vs. CO2 laser conization for pre-invasive lesions. Materials and Methods: We retrospectively analyzed women who underwent CO2 or CK conization for high-grade preinvasive lesions (CIN2/3, CIS and AIS) between 2010 and 2022. Patient demographics, surgical details and pathological outcomes were collected. Pregnancy outcomes, including composite adverse obstetric rates, and oncological follow-up data, were also obtained. Results: In all, 1270 women were included; of them, 1225 (96.5%) underwent CO2, and 45 (3.5%) underwent CK conization. Overall, the rate of positive endocervical or deep margins was lower with CO2 laser compared to CK (4.3% vs. 13.3%, p = 0.015). Incidental CC was diagnosed in 56 (4.4%) patients, with 35 (62.5%) squamous and 21 (46.6%) adenocarcinomas. In a multivariate regression model, the relative risk for positive endocervical or deep margins is significantly greater in cases of incidental diagnosis of CC (p < 0.01). In cases of incidental diagnosis of CC, we found that the probabilities of having either positive endocervical or deep margins after CO2 laser or CK conization are similar, with a higher risk in case of adenocarcinoma lesion. Among women with CC, 42 (75%) opted for radical treatment, while 14 (25%) underwent a follow-up. Only one woman (7.1%) in the follow-up group, who had undergone CK conization, experienced a composite adverse obstetric outcome. No recurrences were observed after a median follow-up of 53 months. Conclusions: CO2 laser conization achieved a lower positive margin rate overall. CK and CO2 conization appear to be equivalent oncological options for incidental CC.

Impact of SARS-CoV-2 Pandemic on the Diagnosis of Cervical Cancer and Precursor Lesions-A Single-Center Retrospective Study.

Background and Objectives: Our aim was to perform a retrospective analysis of the volume of cervical screening tests, the number of patients treated with an excision method, and the incidence of invasive and non-invasive cervical during a pandemic and pre-pandemic period of 24 months. Materials and Methods: The study compared 404 patients who underwent cervical cone biopsy for cervical cancer. The study examined patients' specimens based on histopathological characteristics and categorized cervical lesions based on pap smear. Results: There was a statistically significant age difference between the two study periods. The mean difference was 32 years before the pandemic and 35 years during the pandemic (p-value > 0.05). The biggest patient loss ratio identified by age group was in the 50-59-year group, with a 14.53% loss in the pre-pandemic period and a 9.1% loss in the pandemic period. In the pandemic period, patients from rural areas presented in the clinical trial with a lower rate of 39.52% (83 patients) vs. 60.47% (127 patients) in urban areas. A higher percentage of patients experiencing cervicorrhagia as a clinical manifestation in the pandemic period vs. the pre-pandemic period, with an increase in more severe lesions in the pandemic period, had a statistical significance of 8% more newly diagnosed compared to the pre-pandemic period. Conclusions: The addressability of the patients during the COVID period was not affected in a drastic way in our study. We encountered a decrease in appointments in the age group of 50-59 years and a decrease in patients with rural residence. In our study, we found an increase in cervical bleeding as a reason for consultation in the pandemic period with a higher lesion degree, both on a pap smear and on a cervical biopsy.

Reproductive Outcomes in Young Women with Early-Stage Cervical Cancer Greater than 2 cm Undergoing Fertility-Sparing Treatment: A Systematic Review.

Background and Objectives: Despite advancements in detection and treatment, cervical cancer remains a significant health concern, particularly among young women of reproductive age. Limited data exists in the literature regarding fertility-sparing treatment (FST) of cervical cancers with tumor sizes greater than 2 cm. The objective of this systematic review was to evaluate the reproductive outcomes of women diagnosed with cervical cancer greater than 2 cm who underwent FST. Materials and Methods: A comprehensive search of the literature was carried out on the following databases: MEDLINE, EMBASE, Global Health, The Cochrane Library (Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, Cochrane Methodology Register), the Health Technology Assessment Database, and Web of Science. Only original studies (retrospective or prospective) that reported reproductive outcomes of patients with cervical cancer >2 cm were considered eligible for inclusion in this systematic review (CRD42024521964). Studies describing only the oncologic outcomes, involving FST for cervical cancers less than 2 cm in size, and case reports were excluded. Results: Seventeen papers that met the abovementioned inclusion criteria were included in the present systematic review. In total, 443 patients with a cervical cancer larger than 2 cm were included in this systematic review. Eighty pregnancies occurred, with 24 miscarriages and 54 live births. Conclusions: FST appears to be a viable option for women of childbearing age diagnosed with cervical cancer larger than 2 cm. However, careful consideration is advised in interpreting these encouraging results, as they are subject to limitations, such as variability in study designs and potential biases. In addition, reproductive outcomes should be further cross-referenced with oncologic outcomes to clarify the potential risk-benefit ratio. It is critical to conduct further research using standardized approaches and larger participant groups to strengthen the validity of the conclusions drawn.

Distribution of cervical intraepithelial neoplasia is closely associated with HPV status and uterine position.

Although cervical intraepithelial neoplasia (CIN) lesions are considered to be not randomly distributed across the cervix, but predominantly in the anterior wall, the clinicopathological etiology remains unknown. Herein, we aimed to elucidate the relationship between quantitatively measured area of CIN2/3 and cervical cancer associated factors by retrospective cohort study. We analyzed 235 consecutive therapeutic conization specimens dissected as a single intact section to determine CIN2/3 area and its correlation with both clinical risk factors including human papillomavirus (HPV) status (single or multiple infection) and uterine position defined by transvaginal ultrasound. Cervical wall was classified into three groups: anterior: (11, 12, 1, and 2 o'clock), posterior (5, 6, 7, and 8 o'clock) and lateral (3, 4, 9, and 10 o'clock). Multiple regression revealed that younger age and HPV16 status were significantly correlated with CIN2/3 area (p = 0.0224 and p = 0.0075, respectively). The Jonckheere-Terpstra test showed a significant trend: CIN2/3 area was highest in the single HPV16 group, followed by the multiple HPV16 group and the non-HPV16 group (p < 0.0001). CIN2/3 area in the anterior wall was statistically significantly larger than the posterior and lateral wall (p = 0.0059 and p = 0.0107, respectively). CIN2/3 area in the anterior wall was significantly greater with anteversion-anteflexion than retroversion-retroflexion (p = 0.0485), whereas CIN2/3 area in the posterior wall was significantly larger with retroversion-retroflexion than anteversion-anteflexion (p = 0.0394). In conclusion, the topographical distribution of CIN2/3 area is closely associated with patient age, high-risk HPV status, especially single HPV16 infection and uterine position.

Evaluation of the clinical efficacy of vaginal treatment options for persistent high-risk human papillomavirus infection after excisional treatment of cervical high-grade squamous intraepithelial lesions: a systematic review and Bayesian network meta-analysis.

BACKGROUND: To evaluate the clinical efficacy of different vaginal administration on cervical persistent high-risk human papillomavirus (HR-HPV) infection after excisional treatment for high-grade squamous intraepithelial lesions (HSIL). METHODS: Six databases (PubMed, EmBase, Cochrane Central, China Knowledge Network database, China Biomedical Literature Service, and WanFang database) were searched to collect randomized controlled trials (RCTs) of various types of vaginal administration compared to no treatment on persistent HR-HPV infection after HSIL excisional treatment, and comprehensive analysis of the clearance of different drugs on HR-HPV was performed using Bayesian reticulation meta-analysis. RESULTS: The study analyzed the efficacy of eight interventions, including Interferon, Baofukang, Paiteling, Bletilla striata Sanhuang Powder, Lactobacilli vaginal capsules, Fuanning + Interferon, Interferon + Lactobacilli vaginal capsules, and Interferon + Baofukang, on the clearance of HR-HPV after excisional treatment through pooling and analyzing data from 52 RCTs. The results of the study demonstrated that Interferon + Lactobacilli vaginal capsules [OR 16.0 (95% CIs 8.1-32.0)], Interferon + Fuanning [OR 16.0 (95% CIs 1.1-52.0)], and Interferon + Baofukang [OR 14.0 (95% CIs 6.8-28.0)] were all found to significantly improve postoperative HR-HPV clearance rates when compared to no treatment. Furthermore, when studies with high-risk bias were excluded, Interferon + Lactobacilli vaginal capsules [OR 8.6 (95% CIs 4.7-19.0)] and Interferon + Baofukang [OR 22.0 (95% CIs 8.7-59.0)] were still found to be positively associated with increased postoperative HR-HPV clearance rate. Additionally, the study´s results also indicate that Interferon + Baofukang was effective in enhancing the postoperative HR-HPV clearance rates, mainly when the studies were restricted to a follow-up period of at least 12 months [OR 9.6 (95% CIs 2.9-34.0)]. However, it is important to note that the majority of the trials (29 out of 52, 51.6%) were rated as moderate to high risk of bias, and the certainty of the evidence was moderate to very low. CONCLUSION: The application of various forms of vaginal administration, except for individual use of Lactobacilli vaginal capsules, is more efficacious than no treatment in patients with cervical persistent HR-HPV infection after excisional treatment. However, all of the estimates of the effect size for change in the efficiency of HR-HPV clearance are uncertain. Our confidence in effect estimates and ranking of treatments is low, which needs larger, more rigorous, and longer follow-up RCTs to resolve.

Effect of preoperative cervical conization before hysterectomy on survival and recurrence of patients with cervical cancer: A systematic review and meta-analysis.

OBJECTIVE: Conization plays a therapeutic and diagnostic role in cervical cancer. We conducted a systematic review and meta-analysis to compare the clinical outcomes of patients with cervical cancer who underwent hysterectomy with versus without preoperative cervical conization. METHODS: In this meta-analysis, we analyzed studies published in PubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), International Clinical Trials Registry Platform (ICTRP), and Clinical Trials. gov that appeared in our search from inception to May 1, 2022. RESULTS: Eleven studies with 4184 participants were included in this review. There were 2122 patients in the preoperative conization group and 2062 patients in the non-conization group. The meta-analysis showed that disease free survival (DFS) (hazard ratio [HR]: 0.23; 95% CI: 0.12-0.44; 1616 participants; P = 0.030) and overall survival (OS) (HR: 0.54; 95% CI: 0.33-0.86; 1835 participants; P = 0.597) were improved in the preoperative conization group compared with those in the non-conization group. The risk for recurrence was lower in the preoperative conization group than in the non-conization group (odds ratio [OR]: 0.29; 95% CI: 0.17-0.48; 1099 participants; P = 0.434). There was no significant statistical difference regarding intraoperative adverse events (OR: 0.81; 95% CI: 0.18-3.70; 530 participants; P = 0.555) and postoperative adverse events (OR: 1.24; 95% CI: 0.54-2.85; 530 participants; P = 0.170) between the preoperative conization group and non-conization group. In subgroup analysis, patients who benefited more from preoperative conization, had underwent minimally invasive surgery, had smaller local tumor lesions, and had no lymph node involvement. CONCLUSIONS: Preoperative conization before radical hysterectomy may have a protective effect in the treatment of early cervical cancer, with better survival and less recurrence, especially when the patient is at an early stage and undergoes minimally invasive surgery.

Is minimally invasive radical surgery safe for patients with cervical cancer ≤2 cm in size? (MISAFE): Gynecologic Oncology Research Investigators coLLborAtion study (GORILLA-1003).

OBJECTIVE: To identify clinicopathological factors associated with disease recurrence for patients with 2018 FIGO stage IA with lymphovascular invasion to IB1 cervical cancer treated with minimally invasive surgery (MIS). METHODS: A total of 722 patients with cervical cancer between January 2010 and February 2021 were identified. Clinicopathological factors related to disease recurrence were analyzed. Disease-free survival (DFS) and overall survival (OS) rates were estimated using the Kaplan-Meier method. To determine prognostic factors for DFS, a Cox proportional hazard regression model was used. RESULTS: Of 722 patients, 49 (6.8%) experienced disease recurrence (37 pelvis, 1 para-aortic lymph node, and 11 peritoneum). Five-year DFS and OS rates were 90.7% and 98.1%, respectively. In multivariate analysis, risk factors associated with disease recurrence were residual disease in the remaining cervix (OR, 3.122; 95% CI, 1.152-8.461; p = 0.025), intracorporeal colpotomy (OR, 3.252; 95% CI, 1.507-7.017; p = 0.003), and positive resection margin (OR, 3.078; 95% CI, 1.031-9.193; p = 0.044). The non-conization group had a higher percentage of stage IB1 (77.4% vs. 64.6%; p = 0.004) and larger tumor (10 mm vs. 7 mm; p < 0.001) than the conization group. Intracorporeal colpotomy and residual disease in the remaining cervix were independent variables associated with disease recurrence in patients undergoing MIS following conization. CONCLUSION: During MIS, patients with cervical cancer ≤2 cm in size can be vulnerable to peritoneal recurrences. Patients diagnosed with invasive cancer through conization often have low-risk pathological features, which may affect their survival outcomes.

Conization before radical hysterectomy in patients with early-stage cervical cancer: A Korean multicenter study (COBRA-R).

OBJECTIVE: To investigate the impact of conization on survival outcomes and to identify a specific population that might benefit from conization before radical hysterectomy (RH) in patients with early-stage cervical cancer. METHODS: From six institutions in Korea, we identified node-negative, margin-negative, parametria-negative, 2009 FIGO stage IB1 cervical cancer patients who underwent primary type C RH between 2006 and 2021. The patients were divided into multiple groups based on tumor size, surgical approach, and histology. We performed a series of independent 1:1 propensity score matching and compared the survival outcomes between the conization and non-conization groups. RESULTS: In total, 1254 patients were included: conization (n = 355) and non-conization (n = 899). Among the matched patients with a tumor size of >2 cm, the conization group showed a significantly better 3-year disease-free survival (DFS) rate compared with the non-conization group when RH was conducted via minimally invasive surgery (MIS), in those with squamous cell carcinoma (96.3% vs. 87.4%, P = 0.007) and non-squamous cell carcinoma (97.0% vs. 74.8%, P = 0.021). However, no difference in DFS was observed between the two groups among the matched patients with a tumor size of ≤2 cm, regardless of surgical approach or histological type. In patients who underwent MIS RH, DFS significantly worsened as the residual tumor size increased (P < 0.001). CONCLUSION: Cervical conization was associated with a lower recurrence rate in patients with early-stage cervical cancer with a tumor size of >2 cm who underwent primary MIS RH. Cervical conization may be performed prior to MIS RH to minimize the uterine residual tumor.

Increasing trends of cervical conization with lymph node evaluation for fertility-sparing surgery in early cervical cancer.

OBJECTIVE: To examine uptake, characteristics, and survival outcome of less-radical fertility-sparing surgery with cervical conization and lymph node evaluation (Cone-LN) in reproductive age patients with early cervical cancer. METHODS: This retrospective cohort study examined the National Cancer Institute's Surveillance, Epidemiology, and End Results Program. The study population included 407 patients aged <50 years with stage IA-IB2 (≤4 cm) cervical cancer who received fertility-sparing surgery from 2004 to 2019. The exposure was fertility-sparing surgery type: Cone-LN (n = 196) or trachelectomy with lymph node evaluation (Trach-LN, n = 211). The main co-outcomes were (i) temporal trends of surgery type, assessed with Cochran-Armitage test, and (ii) clinical and tumor characteristics, assessed with multivariable binary logistic regression model. The secondary outcome was overall survival, assessed with inverse probability of treatment weighting propensity score. RESULTS: The number of patients receiving Cone-LN increased from 43.5% in 2004-2007 to 58.4% in 2016-2019 (P-trend = 0.005). Patients receiving conization and sentinel lymph node (SLN) biopsy alone increased from 0% to 14.4% (P-trend < 0.001). In a multivariable analysis, patients in the Cone-LN group were more likely to undergo SLN biopsy (aOR 6.04) compared to those in the Trach-LN group whereas those with adenocarcinoma (aOR 0.49) and T1b tumors (aOR for ≤2 cm 0.21, and aOR for 2.1-4.0 cm 0.10) were less likely to receive Cone-LN. In a propensity score-weighted model, the Cone-LN and Trach-LN groups had comparable overall survival (7-year rates, 98.9% vs 97.8%). Similar associations were observed for patients with squamous, adenocarcinoma / adenosquamous, T1a classification, and T1b(≤2 cm) classification. CONCLUSION: The current population-based analysis suggests that the performance of cervical conization with lymph node evaluation, particularly with SLN biopsy, is gradually increasing for early cervical cancer patients desiring future fertility.

Analysis of risk factors for recurrence in cervical cancer patients after fertility-sparing treatment: The FERTIlity Sparing Surgery retrospective multicenter study.

BACKGROUND: Fertility-sparing treatment in patients with cervical cancer should, in principle, follow identical algorithms to that in patients without future reproductive plans. In recent years, a trend toward nonradical procedures, such as conization or simple trachelectomy, has become apparent in medical literature, because of their associations with better pregnancy outcomes. However, the published reports included small numbers of patients and heterogenous treatment strategies to ascertain the safety of such approaches. OBJECTIVE: This study aimed to collect multi-institutional data regarding the oncological outcomes after fertility-sparing treatment in patients with cervical cancer and to identify prognostic risk factors, including the influence of the radicality of individual cervical procedures. STUDY DESIGN: Patients aged 18 to 40 years with International Federation of Gynecology and Obstetrics 2018 stage IA1 with positive lymphovascular space invasion or ≥IA2 cervical cancer who underwent any type of fertility-sparing procedure were eligible for this retrospective observational study, regardless of their histotype, tumor grade, and history of neoadjuvant chemotherapy. Associations between disease- and treatment-related characteristics with the risk of recurrence were analyzed. RESULTS: A total of 733 patients from 44 institutions across 13 countries were included in this study. Almost half of the patients had stage IB1 cervical cancer (49%), and two-thirds of patients were nulliparous (66%). After a median follow-up of 72 months, 51 patients (7%) experienced recurrence, of whom 19 (2.6%) died because of the disease. The most common sites of recurrence were the cervix (53%) and pelvic nodes (22%). The risk of recurrence was 3 times higher in patients with tumors >2 cm in size than in patients with smaller tumors, irrespective of the treatment radicality (19.4% vs 5.7%; hazard ratio, 2.982; 95% confidence interval, 1.383-6.431; P=.005). The recurrence risk in patients with tumors ≤2 cm in size did not differ between patients who underwent radical trachelectomy and patients who underwent nonradical (conization and simple trachelectomy) cervical procedures (P=.957), regardless of tumor size subcategory (<1 or 1-2 cm) or lymphovascular space invasion. CONCLUSION: Nonradical fertility-sparing cervical procedures were not associated with an increased risk of recurrence compared with radical procedures in patients with tumors ≤2 cm in size in this large, multicenter retrospective study. The risk of recurrence after any type of fertility-sparing procedure was significantly greater in patients with tumors >2 cm in size.

Cervical excisional treatment increases the risk of intraamniotic infection in subsequent pregnancy complicated by preterm prelabor rupture of membranes.

BACKGROUND: Excisional treatment of cervical intraepithelial neoplasia or very early stages of cervical cancer increases the risk of preterm prelabor rupture of membranes in subsequent pregnancies. The risk increases with the length of the excised cone. The subset of cases with preterm prelabor rupture of membranes and a history of cervical excisional treatment could also be at higher risk of intraamniotic infection/inflammation. However, there is a paucity of relevant information on this subject. OBJECTIVE: This study aimed to assess the differences in the rates of intraamniotic infection/inflammation and early-onset neonatal sepsis between singleton preterm prelabor rupture of membranes pregnancies without and with a history of cervical excisional treatment, and to investigate the association between these complications of preterm prelabor rupture of membranes and the excised cone length. STUDY DESIGN: This retrospective cohort study included 770 preterm prelabor rupture of membranes pregnancies in which transabdominal amniocentesis was performed as part of standard clinical management to assess the intraamniotic environment. The maternal and perinatal medical records of all included women were reviewed to obtain information on the absence or presence of history of cervical excisional treatment and neonatal outcomes. Women whose records contained any information on history of cervical excisional treatment were contacted by phone and in writing to inform them of the study and request permission to collect relevant information from their medical records. Women were divided into 4 subgroups according to the presence of microorganisms and/or their nucleic acids (through culturing and molecular biology methods) in amniotic fluid and/or intraamniotic inflammation (through amniotic fluid interleukin-6 concentration evaluation): intraamniotic infection (presence of both), sterile intraamniotic inflammation (intraamniotic inflammation alone), microbial invasion of the amniotic cavity without inflammation (presence of microorganisms and/or their nucleic acids in amniotic fluid alone), and negative amniotic fluid for infection/inflammation (absence of both). RESULTS: A history of cervical excisional treatment was found in 10% (76/765) of the women. Of these, 82% (62/76) had a history of only 1 treatment, and information on cone length was available for 97% (60/62) of them. Women with a history of cervical excisional treatment had higher rates of intraamniotic infection (with, 25% [19/76] vs without, 12% [85/689]; adjusted odds ratio, 2.5; adjusted P=.004), microbial invasion of the amniotic cavity without inflammation (with, 25% [19/76] vs without, 11% [74/689]; adjusted odds ratio, 3.1; adjusted P<.0001), and early-onset neonatal sepsis (with, 8% [11/76] vs without, 3% [23/689]; adjusted odds ratio, 2.9; adjusted P=.02) compared with those without such history. Quartiles of cone length (range: 3-32 mm) were used to categorize the women into 4 quartile subgroups (first: 3-8 mm; second: 9-12 mm; third: 13-17 mm; and fourth: 18-32 mm). Cone length of ≥18 mm was associated with higher rates of intraamniotic infection (with, 29% [5/15] vs without, 12% [85/689]; adjusted odds ratio, 3.0; adjusted P=.05), microbial invasion of the amniotic cavity without inflammation (with, 40% [6/15] vs without, 11% [74/689]; adjusted odds ratio, 6.1; adjusted P=.003), and early-onset neonatal sepsis (with, 20% [3/15] vs without, 3% [23/689]; adjusted odds ratio, 5.7; adjusted P=.02). CONCLUSION: History of cervical excisional treatment increases risks of intraamniotic infection, microbial invasion of the amniotic cavity without inflammation, and development of early-onset neonatal sepsis in a subsequent pregnancy complicated by preterm prelabor rupture of membranes.

Risk stratification of invasive cervical cancer diagnosed after cervical conization.

BACKGROUND: Cervical intraepithelial neoplasia (CIN) diagnosis is based on colposcopy-aided histological examination. However, its accuracy in CIN diagnosis is limited. Some invasive cervical cancers (ICCs) are diagnosed after cervical conization. Therefore, risk stratification of undetected ICC is particularly important for the management of patients with CIN. This study aimed to identify the risk factors for undetected ICC. We especially focused on the association of human papillomavirus (HPV) genotypes. METHODS: We retrospectively reviewed the clinicopathological characteristics (including age, parity, and preoperative diagnosis) and HPV genotypes of 348 patients diagnosed with CIN or adenocarcinoma in situ (AIS) who underwent cervical conization at our hospital between 2008 and 2016. The relationship between preoperative factors, including HPV genotypes and post-conization ICC, was evaluated. RESULTS: Among the 348 patients, 322, 7, and 19 had preoperative CIN3, CIN2, and AIS, respectively; 181 were nulliparous. The median patient age was 41 (23-83) years. HPV genotyping was performed on 237 patients. Overall, post-conization ICC was detected in 16 patients (4.6%). Multivariate analysis showed that nulliparity and HPV16 positivity were the independent risk factors for post-conization ICC (OR: 6.01, P = 0.0302; OR: 5.26, P = 0.0347, respectively). The combination of HPV16 status and parity improved diagnostic accuracy. Seven of 53 HPV16-positive cases (13%) without childbirth history were diagnosed with post-conization ICC. In contrast, none of the HPV16-negative cases with childbirth history was diagnosed with post-conization ICC. CONCLUSION: HPV16 positivity and nulliparity were identified as risk factors for undetected ICC. Careful treatment selection and preoperative scrupulous examination are especially important in these cases.