SUCCOR cone study: conization before radical hysterectomy.

OBJECTIVE: To evaluate disease-free survival of cervical conization prior to radical hysterectomy in patients with stage IB1 cervical cancer (International Federation of Gynecology and Obstetrics (FIGO) 2009). METHODS: A multicenter retrospective observational cohort study was conducted including patients from the Surgery in Cervical Cancer Comparing Different Surgical Aproaches in Stage IB1 Cervical Cancer (SUCCOR) database with FIGO 2009 IB1 cervical carcinoma treated with radical hysterectomy between January 1, 2013, and December 31, 2014. We used propensity score matching to minimize the potential allocation biases arising from the retrospective design. Patients who underwent conization but were similar for other measured characteristics were matched 1:1 to patients from the non-cone group using a caliper width ≤0.2 standard deviations of the logit odds of the estimated propensity score. RESULTS: We obtained a weighted cohort of 374 patients (187 patients with prior conization and 187 non-conization patients). We found a 65% reduction in the risk of relapse for patients who had cervical conization prior to radical hysterectomy (hazard ratio (HR) 0.35, 95% confidence interval (CI) 0.16 to 0.75, p=0.007) and a 75% reduction in the risk of death for the same sample (HR 0.25, 95% CI 0.07 to 0.90, p=0.033). In addition, patients who underwent minimally invasive surgery without prior conization had a 5.63 times higher chance of relapse compared with those who had an open approach and previous conization (HR 5.63, 95% CI 1.64 to 19.3, p=0.006). Patients who underwent minimally invasive surgery with prior conization and those who underwent open surgery without prior conization showed no differences in relapse rates compared with those who underwent open surgery with prior cone biopsy (reference) (HR 1.94, 95% CI 0.49 to 7.76, p=0.349 and HR 2.94, 95% CI 0.80 to 10.86, p=0.106 respectively). CONCLUSIONS: In this retrospective study, patients undergoing cervical conization before radical hysterectomy had a significantly lower risk of relapse and death.

ConCerv: a prospective trial of conservative surgery for low-risk early-stage cervical cancer.

OBJECTIVE: The objective of the ConCerv Trial was to prospectively evaluate the feasibility of conservative surgery in women with early-stage, low-risk cervical cancer. METHODS: From April 2010 to March 2019, a prospective, single-arm, multicenter study evaluated conservative surgery in participants from 16 sites in nine countries. Eligibility criteria included: (1) FIGO 2009 stage IA2-IB1 cervical carcinoma; (2) squamous cell (any grade) or adenocarcinoma (grade 1 or 2 only) histology; (3) tumor size <2 cm; (4) no lymphovascular space invasion; (5) depth of invasion <10 mm; (6) negative imaging for metastatic disease; and (7) negative conization margins. Cervical conization was performed to determine eligibility, with one repeat cone permitted. Eligible women desiring fertility preservation underwent a second surgery with pelvic lymph node assessment, consisting of sentinel lymph node biopsy and/or full pelvic lymph node dissection. Those not desiring fertility preservation underwent simple hysterectomy with lymph node assessment. Women who had undergone an 'inadvertent' simple hysterectomy with an unexpected post-operative diagnosis of cancer were also eligible if they met the above inclusion criteria and underwent a second surgery with pelvic lymph node dissection only. RESULTS: 100 evaluable patients were enrolled. Median age at surgery was 38 years (range 23-67). Stage was IA2 (33%) and IB1 (67%). Surgery included conization followed by lymph node assessment in 44 women, conization followed by simple hysterectomy with lymph node assessment in 40 women, and inadvertent simple hysterectomy followed by lymph node dissection in 16 women. Positive lymph nodes were noted in 5 patients (5%). Residual disease in the post-conization hysterectomy specimen was noted in 1/40 patients-that is, an immediate failure rate of 2.5%. Median follow-up was 36.3 months (range 0.0-68.3). Three patients developed recurrent disease within 2 years of surgery-that is, a cumulative incidence of 3.5% (95% CI 0.9% to 9.0%). DISCUSSION: Our prospective data show that select patients with early-stage, low-risk cervical carcinoma may be offered conservative surgery.

Long-term oncological outcomes and recurrence patterns in early-stage cervical cancer treated with minimally invasive versus abdominal radical hysterectomy: The Norwegian Radium Hospital experience.

OBJECTIVE: To compare long-term oncological outcomes in early-stage cervical cancer (CC) patients treated with minimally invasive radical hysterectomy (MIRH) versus abdominal radical hysterectomy (ARH), with a focus on recurrence patterns, tumor sizes, and conization. METHODS: This single-institution, retrospective study consisted of stage IA1-IB1 (FIGO 2009) squamous cell carcinoma, adenocarcinoma, and adenosquamous carcinoma of the cervix, who underwent radical hysterectomy between 2000 and 2017. RESULTS: Of the 582 patients included, 353 (60.7%) underwent ARH, and 229 (39.3%) MIRH. The median follow-up was 14.4 years in the ARH group and 6.1 years in the MIRH group (p < 0.0001). Among the 96 stage IA patients, only 3 (3.1%) experienced recurrence. Among stage IB1 patients, the risk of recurrence, after adjusting for standard prognostic variables, was twofold higher in the MIRH group versus the ARH group (HR 2.73, 95% CI: 1.56-4.80), and the relative difference was similar in terms of risk of cancer-specific survival (CSS) (HR 3.04, 95% CI: 1.28-7.20) and overall survival (OS) (HR 2.35, 95% CI: 1.21-4.59). In stage IB1 ≤ 2 cm patients without conization MIRH was associated with reduced time to recurrence (TTR) (HR 4.00, 95% CI: 1.67-9.57), CSS (HR 3.71, 95% CI: 1.19-11.58) and OS (HR 3.02, 95% CI: 1.24-7.34). Intraperitoneal combined recurrences accounted for 12 of 30 (40.0%) recurrences in the MIRH group but were not identified after ARH (p = 0.0001). CONCLUSIONS: MIRH was associated with reduced TTR, CSS and OS versus ARH in stage IB1 CC patients. The risk of peritoneal recurrence was high, even for tumors ≤2 cm without conization.

Pathologic Determination of Multifocality in pT1a1 Squamous Cell Carcinoma of the Cervix: A Retrospective Analysis.

When more than one focus of stromal invasion is present in a superficially invasive cervical squamous cell carcinoma (SCC), determination of the tumoral lateral extent/horizontal extension, and hence tumor-nodes-metastases (TNM) staging, can be problematic. In recent years, a diagnostic approach to distinguish multifocal pT1a1 from pT1b cases has gained increased attention. These criteria call for classifying SCC as multifocal when invasive foci are separated by blocks of uninvolved cervical tissues, and/or are located on separated cervical lips in a tumor that is discontinuous, and/or are situated far apart (≥2 mm) from each other. In this study, we assess our experience with multifocal stage pT1a1 cervical SCC that was retrospectively classified as such using these criteria. Slides from the loop electrosurgical excision or conization specimens, comprising 212 pT1a1, 173 pT1a2, and 206 pT1b cases, were reviewed. Twenty-four (11%) of the 212 pT1a1 cases were classified as multifocal after review. The 24 multifocal pT1a1 cases were compared with the 188 unifocal pT1a1 cases regarding a variety of clinicopathologic parameters. Notably, these 2 groups showed no significant differences regarding all parameters that were evaluated, including patient age, recurrence rate, primary tumoral features in the primary excision specimen (rate of positive margins, median depth of stromal invasion, frequency of lymphovascular invasion), and frequency of residual disease in additional excisions. In summary, we demonstrate comparably favorable patient outcomes in both unifocal and multifocal cases of pT1a1 SCC of the cervix, and, accordingly, we conclusively affirm the validity of the aforementioned criteria for establishing multifocality.

Preoperative Conization and Risk of Recurrence in Patients Undergoing Laparoscopic Radical Hysterectomy for Early Stage Cervical Cancer: A Multicenter Study.

STUDY OBJECTIVE: To investigate the factors associated with poorer oncologic outcomes in patients undergoing laparoscopic radical hysterectomy (LRH) for early stage cervical cancer. DESIGN: Multicenter retrospective study. SETTING: Three gynecologic oncology referral centers. PATIENTS: Patients with International Federation of Gynecology and Obstetrics 2009 stage IA (positive lymphovascular space invasion)-IB1 cervical cancer between January 2006 and June 2018. INTERVENTIONS: LRH (Piver type II-III hysterectomies). Lymph-node dissection was accomplished according to the tumor characteristics. MEASUREMENTS AND MAIN RESULTS: Surgical and oncologic outcomes were analyzed. Overall, 186 patients met the inclusion criteria, 16 (8.6%) experienced a recurrence, and 9 (4.8%) died of the disease (median follow-up period 37.9 months). Surgery-related complications did not influence disease-free survival. All the recurrences (16/16; 100%) occurred in patients with stage IB1 disease (p = .02), and 15 (93.7%) in cases involving tumors ≥2 cm. No association between positive lymph node and recurrence was detected (p =.82). Patients who had a preoperative diagnosis through conization (93; 50%) had a significantly lower rate of recurrence than those who underwent cervical biopsy (93; 50%): 1/93 (1.1%) vs 15/93 (16.1%); p <.001). The subanalysis of patients with International Federation of Gynecology and Obstetrics stage IB1 cervical cancer showed that patients undergoing preoperative conization (vs cervical biopsy) were less likely to experience a recurrence (odds ratio 0.09; 95% confidence interval 0.01-0.55). CONCLUSION: We confirmed that LRH was associated with a recurrence rate similar to that reported in the Laparoscopic Approach to Cervical Cancer trial. Tumor size ≥2 cm represents the most important risk factor influencing disease-free survival. However, we found that preoperative conization plays a potentially protective role in patients with an IB1 tumor.

The relationship of human papillomavirus infection with endocervical glandular involvement on cone specimens in women with cervical intraepithelial neoplasia.

OBJECTIVE: The aim of study was to evaluate the association of endocervical gland involvement (EGI) on histological samples with high risk (HR) human papillomavirus (HPV) infection and with the persistence/recurrence rate of cervical intraepithelial neoplasia (CIN) after treatment. METHODS: A total of 1301 subjects who had conization procedures after cervical punch biopsies (533 persistent CIN1, 768 CIN2+ including 20 microinvasive cervical cancer) were enrolled in the study. HPV genotypes were identified using the INNO-LiPA HPV genotyping assay on cervical scraping. Logistic regression and Cox regression analyses were used to evaluate the association of EGI on the persistence/recurrence rate of CIN after treatment. RESULTS: The rate of EGI on final histology was 46.3% (602/1301). HPV 16 was the only HR-HPV significantly associated with increasing rates of EGI (231/602 as compared to 211/699, p = 0.002). EGI was also associated with an excess of multiple HR-HPV infections (237/602 as compared with 225/699, p = 0.006). After correction for confounders, the odds ratio of EGI among women infected by HPV 16 was 1.41 (95% CI = 1.12-178). CIN2+ lesions were diagnosed in 40.5% (283/699) of EGI negative subjects and 86.7% (522/602, p < 0.001 compared to negative subjects) of EGI positive subjects.After a median of 25 months of follow-up (IQR = 15-47) of 1090 treated women, the persistence of HPV 16 during follow-up was 38.1% (93/217, p = 0.03 compared to EGI negative) among EGI positive and 32% (58/181) among controls. After corrections for potential confounders, the odds ratio of CIN2+ persistence and or recurrence was higher among EGI positive (OR = 2.35, 95% CI = 1.16-4.77) than negative controls. CONCLUSION: EGI on histological samples is associated with increased rates of HPV 16, multiple high risk-HPV infections and CIN2+ lesions. EGI positive subjects also had an increased CIN recurrence/persistence after treatment compared to controls.

Pathologic and clinical tumor size discordance in early-stage cervical cancer: Does it matter?

OBJECTIVE: The objective of this study was to assess the rate of discordance between clinical and pathologic tumor size for women with stage IB1 cervical cancer (FIGO 2009 criteria), assess risk factors for discordance, and determine the impact of discordance on oncologic outcomes. METHODS: This was a secondary analysis of a prior multi-institutional retrospective review of patients diagnosed with stage IB1 (FIGO 2009 staging) cervical cancer undergoing radical hysterectomy between 2010 and 2017. Demographic, clinicopathologic, and oncologic data were collected. Pathologic upstaging was defined as having a preoperative diagnosis of stage IB1 cervical cancer with pathology demonstrating a tumor size >4 cm. Demographic and clinicopathologic data was compared using chi-square, fisher exact or 2-sided t-test. Survival was estimated using the Kaplan-Meier method. RESULTS: Of the 630 patients, 77 (12%) were upstaged. Patients who were upstaged had lower rates of preoperative conization (p < .001) or preoperative tumor sizes ≤2 cm (p < .001). Upstaged patients had increased odds of deep stromal invasion, lymphovascular space invasion, positive margins and positive lymph nodes. Almost 88% of upstaged patients received adjuvant therapy compared to 29% of patients with tumors ≤4 cm (odds 18.49, 95% CI 8.99-37.94). Finally, pathologic upstaging was associated with an increased hazard of recurrence (hazard ratio [HR] 1.95, 95% CI 1.03-3.67) and all-cause death (HR 2.31, 95% CI 1.04-5.11). CONCLUSIONS: Pathologic upstaging in stage IB1 cervical cancer is relatively common. Upstaging is associated with an 18-fold increased risk of receipt of adjuvant therapy. Patients undergoing preoperative conization and those with tumors <2 cm had lower risks of upstaging. Improvement in preoperative assessment of tumor size may better inform primary treatment decisions.

Predictors of recurrence following laparoscopic radical hysterectomy for early-stage cervical cancer: A multi-institutional study.

OBJECTIVE: To assess predictors of recurrence following laparoscopic radical hysterectomy (LRH) for apparent early stage cervical cancer (CC). METHODS: This is a retrospective multi-institutional study reviewing data of consecutive patients who underwent LRH for FIGO 2009 stage IA1 (with lymphovascular space invasion (LVSI)), IA2 and IB1(≤4 cm) CC, between January 2006 and December 2017. The following histotypes were included: squamous, adenosquamous, and adenocarcinoma. Multivariable models were used to estimate adjusted odds ratio (OR) and corresponding 95% CI. Factors influencing disease-free survival (DFS) and disease-specific survival (DSS) were also explored. RESULTS: 428 patients were included in the analysis. With a median follow-up of 56 months (1-162) 54 patients recurred (12.6%). At multivariable analysis, tumor size (OR:1.04, 95%CI:1.01-1.09, p = .02), and presence of cervical residual tumor at final pathology (OR: 5.29, 95%CI:1.34-20.76, p = .02) were found as predictors of recurrence; conversely preoperative conization reduced the risk (OR:0.32, 95%CI:0.11-0.90, p = .03). These predictors remained significant also in the IB1 subgroup: tumor size: OR:1.05, 95%CI:1.01-1.09, p = .01; residual tumor at final pathology: OR: 6.26, 95%CI:1.58-24.83, p = .01; preoperative conization: OR:0.33, 95%CI:0.12-0.95, p = .04. Preoperative conization (HR: 0.29, 95%CI: 0.13-0.91; p = .03) and the presence of residual tumor on the cervix at the time of surgery (HR: 8.89; 95%CI: 1.39-17.23; p = .01) independently correlated with DFS. No independent factors were associated with DSS. CONCLUSIONS: In women with early stage CC the presence of high-volume disease at time of surgery represent an independent predictor of recurrence after LRH. Conversely, preoperative conization and the absence of residual disease at the time of surgery might play a protective role.

Loop Electrosurgical Excision Procedure or Cervical Conization to Exclude Cervical Cancer Before Simple Hysterectomy.

OBJECTIVE: The aim of the study was to determine which women require loop electrosurgical excision procedure (LEEP) or cervical conization (cone) to exclude cervical cancer after colposcopy for evaluation of abnormal cervical cancer screening tests yet before simple hysterectomy. MATERIALS AND METHODS: Review of electronic medical records from colposcopy clinics followed by chart review of women with cervical cancer was conducted. RESULTS: Of 18,537 cervical colposcopies for evaluation of abnormal cervical cancer screening tests, 0.6% (103/18,537) had cervical cancer; of 103 women with cervical cancer, 57 had neither cervical biopsy nor endocervical curettage (ECC) showing cancer or rule-out cancer (occult cancers) and were diagnosed by subsequent LEEP (n = 22), cone (n = 31), failed cone (n = 1), or hysterectomy (n = 3). The relative risk of occult cervical cancer at colposcopy for ECC of cervical intraepithelial neoplasia (CIN) 2 or CIN 3 versus ECC not CIN 2 or CIN 3 was 51.5 (5.0% vs 0.1%), for cervical biopsy of CIN 3 versus not CIN 3, was 34.5 (3.9% vs 0.1%), and for colposcopic impression of CIN 2, CIN 3, or cancer (CIN 2+) versus impression not CIN 2+, was 8.5 (1.9% vs 0.2%). If the 10.9% (2,018/18,537) of colposcopies with ECC of CIN 2 or CIN 3, cervical biopsy of CIN 3, or colposcopic impression of CIN 2+ had subsequent LEEP or cone, 96.5% (55/57) of occult cervical cancers would be detected before hysterectomy. CONCLUSIONS: After colposcopy, women with ECC of CIN 2 or CIN 3, cervical biopsy of CIN 3, or colposcopic impression of CIN 2+ require LEEP or cone before simple hysterectomy.

Post-conization follow-up of patients with CIN 2/3 with different amount of distance to negative cone biopsy margin: a retrospective cohort study.

The aim of this study was to investigate whether patients with CIN 2/3 with different amount of distance to negative cone biopsy margin differ in terms of post-conization follow-up results. Cold-knife cone specimens with a negative surgical margin with a diagnosis of CIN-2/3 were selected. The minimum distance between the margin and lesion was categorised as less than 2 mm (Group-1), 2-5 mm (Group-2), or more than 5 mm (Group-3). There were no statistically significant differences between groups in terms of postoperative cone-biopsy results (p = .61). Furthermore, there were no statistically significant differences between groups in terms of cytology at 6 months and 12 months (p = .33 and p = .80, respectively). Results of the present study indicate that the amount of distance of lesion to cone biopsy margin seems to have no effect on follow-up results in patients with negative surgical margin.Impact StatementWhat is already known on this subject? Negative surgical margins on conization are associated with lower rates of lesion recurrence. Only the efficacy of volume and size of cone biopsy specimens have been analysed on lesion recurrence. However, there is no clear definition of the minimum distance of a negative margin during cone biopsy.What do the results of this study add? To the best of our knowledge, this is the first study describing the post-conization follow-up of patients with CIN 2/3 with different amount of distance to negative cone biopsy margin. Patients who underwent surgical treatment with a wider cone biopsy margin and narrower cone biopsy margin demonstrated similar follow-up results.What are the implications of these findings for clinical practice and/or further research? The present study provides valuable information to guide physicians performing conizations with an appropriate amount of negative surgical margin. Future studies investigating the effect of different amount of distance to negative cone biopsy margin on gynaecologic and obstetrics complications such as stenosis, bleeding, and preterm labour, low birth weight, and perinatal mortality are needed to show the benefits of a narrower distance to negative cone biopsy margin.

Colposcopic and histopathologic evaluation of women with HPV persistence exiting an organized screening program.

BACKGROUND: Human papillomavirus-based screening has a higher sensitivity for precursors of cervical cancer compared with cytology-based screening. However, more evidence is needed on optimal management of human papillomavirus-positive women. OBJECTIVE: The objective of the study was to compare the risk of histopathologically confirmed cervical intraepithelial lesions grade 2 or worse after 1 and 3 years of human papillomavirus persistence, respectively, and evaluate the clinical management of human papillomavirus-positive women in the 56-60 year age group. STUDY DESIGN: This was a randomized health care policy offering human papillomavirus screening to 50% of resident women aged 56-60 years in the Stockholm/Gotland region of Sweden during January 2012 through May 2014. Women who were human papillomavirus positive/cytology negative at baseline were referred for a repeat test after 1 or 3 years. In case of human papillomavirus persistence, women were referred for colposcopy, including biopsies and endocervical sampling. RESULTS: The human papillomavirus prevalence was 5.5% (405 women of 7325 attending). Among the 405 human papillomavirus-positive women, 313 were reflex test cytology negative at baseline and were referred for a repeat human papillomavirus test, 176 women after 1 year and 137 women after 3 years. After 1 year, 91 of 176 (52%) were persistently human papillomavirus positive and after 3 years 55 of 137 (40%) (P = .042). In repeat cytology, 10 of the 91 (12%) were positive after 1 year and 15 of 55 (33%) after 3 years (P = .005). The attendance rates for colposcopy were similar: 82 of 91 (90%) in the 1 year group and 45 of 55 (82%) in the 3 year group. All women attending colposcopy were postmenopausal, and endocervical sampling and punch biopsies were performed to facilitate colposcopic management, with a positive predictive value of 43-50% and 28-31%, respectively. Histopathologically confirmed cervical intraepithelial lesions grade 2 or worse was found in 19 of 82 women (23%) and 9 of 45 women (20%) in the 1 year and 3 year groups, respectively, and registry linkage follow-up found no cancers in either group. Human papillomavirus genotyping was predictive of cervical intraepithelial lesions grade 2 or worse, and human papillomavirus 16 was the most common genotype at human papillomavirus persistence, occurring in 18% of the cases in the 1 year group and 20% in the 3 year group. CONCLUSION: It was safe to postpone repeat human papillomavirus tests for 3 years in postmenopausal women attending the organized cervical screening program. There was a high risk for cervical intraepithelial lesions grade 2 or worse at follow-up and noteworthy yields from human papillomavirus genotyping as well as endocervical sampling and random biopsies in the absence of visible colposcopic lesions.

Maternal History of Cervical Surgery and Preterm Delivery: A Retrospective Cohort Study.

Introduction: Our aim was to investigate whether cervical conization and/or loop electrosurgical excision procedure (LEEP) increases the risk of preterm delivery. Materials and Methods: We conducted a retrospective cohort study of singleton deliveries at our institution from 2010 to 2015. Women aged 16-49 years were included in our study. Univariate and logistic regression were used for statistical analyses. An interaction test was used to assess whether maternal human papillomavirus (HPV) positivity within the 3 years before delivery (referred to as maternal HPV status in this study) is an effect modifier. Results: Of 3933 women who delivered at our institution, 19.8% (n = 792) delivered prematurely. Of these women, 9.1% (n = 362) had a history of cervical surgery, including cervical conization and/or LEEP. Notably, a history of cervical surgery was not associated with current HPV status based on the most recent Pap smear results (p > 0.05). In univariate analysis, a history of cervical surgery was associated with preterm delivery (odds ratio [OR] = 1.54, 95% confidence interval [CI]: 1.26-1.88). This effect was the same among mothers positive (OR = 1.95, 95% CI: 1.16-3.28) and negative (OR = 1.91, 95% CI: 1.10-3.30) for HPV. Pregnancy-induced hypertension, preterm premature rupture of membranes, bacterial vaginosis infection, HPV infection, placenta previa, placental abruption, ethnicity, maternal body mass index, nulliparity, and smoking or drug use were also associated with preterm delivery (p < 0.05). In multivariable analysis, history of cervical surgery remained associated with preterm delivery (OR = 1.75, 95% CI: 1.31-2.33). There was no interaction (p = 0.91) between maternal HPV status and history of cervical conization or LEEP. Discussion and Conclusions: Maternal history of cervical conization and/or LEEP increases the risk of preterm delivery irrespective of concurrent maternal HPV positivity within the 3 years preceding delivery. Maternal HPV status does not modify the effect of history of cervical conization and/or LEEP on preterm delivery.

Incidence and costs of cervical intraepithelial neoplasia in the Korean population.

OBJECTIVE: The purpose of this study was to assess the incidence rate of cervical intraepithelial neoplasia (CIN) and cervical cancer, and their costs according to age. METHODS: We collected data on annual incidence and medical costs of CIN and cervical cancer from 2010 until the end of 2014 from the Health Insurance Review and Assessment (HIRA) service. The CIN was classified into CIN3 (high-grade) requiring conization and CIN1/2 (low-grade) requiring observation. RESULTS: Incidence rates of CIN3 and cervical cancer are reducing over time, whereas CIN1/2 is increasing significantly (p for trend: <0.001). The peak ages of incidence were 25-29, 30-34, and 70-74 years old for CIN1/2, CIN3, and cervical cancer, respectively. The crude incidence of CIN1/2 increased by approximately 30% in 2014 compared to 5 years ago and demonstrated an increasing trend in all age groups. The CIN3 showed a significantly increasing trend in the age group of 30-39 years old, the cervical cancer was significantly reduced in all ages, except the 35-39 years old. The treatment for cervical cancer costs $3,342 per year, whereas the treatment for CIN3 and CIN1/2 cost $467 and $83, respectively. CONCLUSION: The crude incidence rate of cervical cancer is currently decreasing among Korean women, but the incidence rates and medical costs of CIN and cervical cancer are increasing in women in their 30s in Korea. These findings suggest that different strategies by age will be required for prevention of cervical cancer in Korea.

Nomogram-based prediction of cervical dysplasia persistence/recurrence.

The widespread introduction of screening methods allow to identify cervical dysplasia before having invasive cancer. The risk of developing cervical dysplasia persistence/ recurrence following conization represent a major health issue. Although several studies tried to identify predictors for cervical dysplasia persistence/recurrence, no previous study has been conducted to develop a risk calculator. The current study aimed to identify predictors of cervical dysplasia persistence/recurrence among women undergoing primary conization. We aimed to build nomograms estimating the risk of developing cervical dysplasia recurrence. Data of consecutive women with diagnosis of high-risk human papillomavirus (HPV) undergoing conization were retrospectively evaluated (1503 patients). The risk of developing cervical dysplasia persistence/recurrence was assessed with Kaplan-Meier and Cox's hazard models. Additionally, two nomograms were built to estimate likelihood of cervical dysplasia recurrence: the first based on baseline and operative parameters and the second focusing on type-specific HPV detected. The performance of the above nomograms was assessed using concordance index. A total of 1503 patients were analyzed. After a mean (SD) follow-up of 48.6 ( ± 17.5) months, 84 (5.6%) patients required secondary conization. By multivariate analysis, HIV infection [hazard ratio (HR): 7.78; 95% confidence interval (CI): 2.77-21.81; P < 0.001], positive margins (HR: 26.2; 95% CI: 14.1-48.71; P < 0.001) and persistence of HPV (HR: 6.82; 95% CI: 4.15-11.21; P < 0.001) correlated with cervical intraepithelial neoplasia 2+ persistence/recurrence. The importance of those variables was corroborated by our first nomogram. The second nomogram suggested the impact of type-specific HPV infection in predicting cervical dysplasia persistence/ recurrence. HPV16, HPV18, HPV33, HPV35 and HPV45 were the HPV types most commonly associated with cervical dysplasia persistence/recurrence. The concordance index was greater than 0.70 for both nomograms, thus suggesting the reproducibility of our models. We developed the first two nomograms predicting this risk. The findings of this study require external validation. Once validated our data might be useful to plan a tailored postoperative surveillance of women receiving primary conization.

The risk factors of residual lesions and recurrence of the high-grade cervical intraepithelial lesions (HSIL) patients with positive-margin after conization.

The aim of this study was to illuminate risks factors of residual lesions, and recurrence of the high-grade cervical intraepithelial lesions (HSIL) patients with positive margin who underwent cervical conization.A retrospective cohort study of 218 patients with positive margin after conization, including cold knife conization (CKC) and loop electrosurgical excisional procedure (LEEP), and follow-up from 2013 through 2016. The diagnosis of residual disease and recurrence were established and confirmed by biopsy. We evaluate the correlations among residual rate, recurrence rate, and clinical parameters, such as age, menopausal status, gravity, parity, glandular involvement, thinprep cytologic test (TCT), and human papillomavirus (HPV) results. We also detect the difference between CKC and LEEP.There was statistical difference between the positive margin rate of CKC group and LEEP regarding the surgery methods (5.8% and 12.09% separately, P < .001). Residual disease was found in 53.66% cases where 41 patients received second surgery after conization. Besides, age (P = .027), menopausal status (P = .006), and HPV infection (P = 0.018) were significantly associated with residual lesion. Among 177 cases with histopathologic follow-up, 15.91% women relapsed from 4 to 27 months. As for recurrence we found it was more frequent with HPV infection and glandular involvement (P < .001). TCT was also an independent factor in patients with recurrence of lesion. No evidence shows difference between CKC and LEEP for recurrence rate (P = .918).The factors related to rate of residual lesion were age, menopausal status, and HPV infection. HPV infection, TCT, and glandular involvement were associated with HSIL recurrence. LEEP was as effective as CKC with regard to recurrence rate. Further large-scale studies are needed to confirm our findings.

Risks of cervical intraepithelial neoplasia grade 3 or invasive cancers in ASCUS women with different management: a population-based cohort study.

OBJECTIVE: To investigate the progression risk of atypical squamous cells of undetermined significance (ASCUS) with different clinical managements. METHODS: Women with their first diagnosis of ASCUS cytology were retrieved from the national cervical cancer screening database and linked to the national health insurance research database to identify the management of these women. The incidences of developing cervical intraepithelial neoplasia grade 3 and invasive cervical cancer (CIN3+) were calculated, and the hazard ratios (HRs) were estimated using a Cox proportional hazards model. This study was approved by the Research Ethics Committee of the National Taiwan University Hospital and is registered at ClinicalTrials.gov (Identifier: NCT02063152). RESULTS: There were total 69,741 women included. Various management strategies including colposcopy, cervical biopsies and/or endocervical curettage, and cryotherapy, failed to reduce the risk of subsequent CIN3+ compared with repeat cervical smears. Loop electrosurgical excision procedure/conization significantly decreased risk of subsequent CIN3+ lesions (HR=0.22; 95% confidence interval [CI]=0.07-0.68; p=0.010). Women in their 40s-50s had an approximately 30% risk reduction compared to other age groups. Women with a previous screening history >5 years from the present ASCUS diagnosis were at increased risk for CIN3+ (HR=1.24; 95% CI=1.03-1.49; p=0.020). CONCLUSION: In women of first-time ASCUS cytology, a program of repeat cytology can be an acceptable clinical option in low-resource settings. Caution should be taken especially in women with remote cervical screening history more than 5 years.

Natural History of Squamous Intraepithelial Lesions in Pregnancy and Mode of Delivery.

BACKGROUND: Numerous studies have addressed the impact of mode of delivery on the natural history of squamous intraepithelial lesions (SIL) in pregnant women. However, the literature is still contradictory. PATIENTS AND METHODS: In the course of a retrospective analysis, data of 63 pregnant women with abnormal cervical smears who were referred to our Outpatient Department for pre-invasive lesions of the cervix were analyzed. The study was conducted at the General Hospital in Vienna, Austria, between 2010 and 2015. Data collection included demographics, delivery route and diagnostic results of cervical lesions by cytology, colposcopy, human papilloma virus (HPV) testing, histological report of punch biopsy and, if applicable, cone biopsy. RESULTS: Among 63 women who met the inclusion criteria, 40 (63%) delivered vaginally and 23 (37%) underwent caesarean section. Postpartum regression of cervical dysplasia was documented in 15 women delivering vaginally and in 10 who had a caesarean section (p=0.641). Among those women who delivered vaginally, three had progression and in 22 women the lesions persisted postpartum. In the group of women with caesarean section, one had progression and the lesions of 12 women persisted after delivery. No woman had progression to invasive disease. CONCLUSION: The mode of delivery does not significantly influence the natural history of cervical dysplastic lesions in pregnant women. The numbers of spontaneous regressions to normal cervical cytology during pregnancy were similar in both groups.

Cervical cancer screening and subsequent procedures in women under the age of 25 years between 2007 and 2013 in France: a nationwide French healthcare database study.

Cervical cancer screening in young women may lead to the detection of lesions with a high potential for spontaneous regression and no benefit of surgery. French guidelines recommend initiating cervical cancer screening by the Pap test from the age of 25 years. To date, no French nationwide study has assessed cervical cancer screening in young women and the related subsequent work-up and surgical procedures among screen-positive women. Using data from the French national healthcare databases (around 50 million beneficiaries), annual and 3-year Pap test screening rates were calculated among women aged 15-24 years between 2007 and 2013. Cervical excisional procedures were assessed during the 15-month period following a first Pap test in women aged 20-24 years in 2007 and 2012. About 10% of the almost six million women aged 15-65 years with at least one annual Pap test were under the age of 25, mainly women aged 20-24 years, in whom the 3-year screening coverage was 35.5% in 2013. In screened women aged 20-24 years, human papillomavirus testing rates increased markedly over the study period (+105%) and surgical management became less conservative with an increased rate of both conization (+16.5%) and other excisional treatments (+74.5%). Nevertheless, because of the overall decrease in screening coverage, the absolute yearly number of women who underwent conization decreased from 1974 to 1766 between 2007 and 2012. Higher adherence to guidelines is needed to reduce the burden of surgical treatment that is potentially associated with adverse obstetric outcomes among women under the age of 25 years.

Long-term risk of cervical cancer following conization of cervical intraepithelial neoplasia grade 3-A Danish nationwide cohort study.

Using nationwide Danish registries we examined the long-term risk of cervical cancer in women diagnosed with cervical intraepithelial neoplasia grade 3 (CIN3) (including adenocarcinoma in situ (AIS)) on the cone compared to women with a normal cytology test. Initially, we identified women born 1918-1990, who were recorded as living in Denmark between January 1, 1978 and December 31, 2012. From the Pathology Data Bank information on CIN3 on the cone, margins status, histological type of CIN3 and cervical cytology results was extracted. Cox proportional hazard model was used to estimate the relative risk of subsequent cervical cancer. We included 59,464 women with CIN3 on the cone and 1,918,508 women with a normal cytology test. Overall, women diagnosed with CIN3 had a higher risk of subsequent cervical cancer compared to women with normal cytology (HR = 2.06; 95%CI: 1.81-2.35). Analyses according to time since conization showed elevated risks in all time periods, and 25 years or more after conization the relative risk was significantly increased (HR = 2.56; 95%CI: 1.37-4.77). Twenty years or more after conization, also women with negative margins had an increased relative risk (HR = 2.49; 95%CI: 1.12-5.57). In addition, the long-term relative risk of cervical cancer varied with the different histological types of CIN3 and was highest for AIS (HR = 7.50; 95%CI: 1.87-30.01, 10-14 years after conization). In conclusion, women diagnosed with CIN3 on the cone have a long-lasting increased risk of cervical cancer even when the margins on the cone are negative.