Unraveling cervical cancer screening dilemmas: histopathological insights from VIA and LEEP at bugando medical centre, Mwanza.

BACKGROUND: The single-visit strategy, also known as the "screen-and-treat" approach, is widely used to screen for cervical cancer in low- and middle-income countries. The screen-and-treat approach leads to unnecessary or inadequate treatment. Thus, a study was conducted to determine the histopathological patterns of aceto-white lesions on visual inspection with acetic acid (VIA) in patients who underwent a Loop Electrosurgical Excision Procedure (LEEP) at Bugando Medical Centre between January 2016 and December 2020. METHOD: A 5-year retrospective cross-sectional case record review was conducted on 329 women who had LEEP at Bugando Medical Centre following a positive VIA cervical screening test. A standard data abstraction form was used to collect patient information. Missing client information records and LEEP without histopathological results were exclusion criteria. For statistical analysis, STATA version 15 was used; in descriptive statistics, frequency, mean, and standard deviation were used. The Chi2 and Fisher's exact tests were used to investigate the relationship between patient characteristics and histopathological patterns, and a P-value of 0.05 was considered statistically significant in multinomial models. RESULTS: This study looked at 329 patients who had LEEP following a VIA positive but were not eligible for cryotherapy. Our study participants had a mean age of 40 ± 8.2 SD. There were 203 (61.7%) patients with benign lesions, including 4 with schistosomiasis and 2 with cervical tuberculosis. The precancerous lesions were discovered in 100 cases (30.4%), and 26 (7.9%) already had invasive cervical cancer. Out of 100 patients with precancerous lesions, 58 (17.6%) and 42 (12.8%) have high- and low-grade squamous intraepithelial (HSIL and LSIL) lesions, respectively. The presence of a precancerous lesion was found to be associated with age 31-40 years (P-value 0.042) and HIV positivity (P-value 0.004). CONCLUSION: Most patients in this study had benign cervical lesions, which do not require LEEP treatment. Nonetheless, a considerable percentage of invasive cervical malignancies and rare benign diseases such as schistosomiasis and cervical tuberculosis were identified. A screen-and-treat approach within well-equipped tertiary hospitals like Bugando Medical Centre should explore alternative options instead of relying solely on straight LEEP.

Leveraging Ecological Momentary Assessment to Examine Bi-directional Associations Between Sleep Quality, Adolescent/Young Adult Alcohol Craving and Use.

BACKGROUND: Alcohol use is common among adolescents and young adults (AYA) and linked to poor sleep quality. Poor sleep quality may also increase alcohol use and alcohol craving, yet bi-directional relations between sleep quality and AYA alcohol use are poorly understood. PURPOSE: This study examined bi-directional associations between sleep quality, alcohol craving, and alcohol use in AYA using ecological momentary assessment (EMA) and explored if biological sex, age, or race moderated these associations. METHODS: This pre-registered secondary analysis pooled EMA data from the baseline, pre-randomization period (M = 8.18 days, range = 1-17) in two double-blind randomized placebo-controlled clinical trials examining medication effects on alcohol use in AYA (N = 115). Each morning, participants reported sleep quality and alcohol consumption (i.e., number of standard drinks) from the previous day, and craving was rated at several random points each day. RESULTS: Multilevel modeling showed that poorer average sleep quality was associated with higher levels of alcohol craving for females but not for males, and better overall levels of sleep quality were associated with decreased likelihood of engaging in alcohol use. No other person- or day-level associations between sleep and alcohol use emerged. CONCLUSIONS: Better sleep quality may be protective against alcohol use in AYA, and female AYA who report poorer sleep quality may experience higher levels of alcohol craving. Research and clinical assessment of AYA sleep quality can contribute to understanding of factors promoting alcohol craving and use.

This study explored how alcohol use among adolescents and young adults influences sleep quality as well as how sleep quality influences alcohol use and alcohol craving. Each morning, for approximately 1 week, participants reported their alcohol use from the prior day and their sleep quality from the prior night. They also rated their alcohol craving several times each day. Results showed that better overall sleep quality was associated with a lower likelihood of alcohol use. Poorer average sleep quality was associated with higher alcohol craving for females but not males. These findings suggest that better sleep quality may protect against alcohol use among youth and serve as a protective factor against alcohol craving for females.

Efficacy of recombinant bovine basic fibroblast growth factor to reduce hemorrhage after cervical loop electrosurgical excision procedure.

OBJECTIVE: It has been reported that recombinant bovine basic fibroblast growth factor (rbFGF) may possess possible biological functions in promoting the process of wound healing. Consequently, our study aimed to investigate the hemostatic effect of topically applied rbFGF in patients who underwent a loop electrosurgical excision procedure (LEEP). METHODS: In this retrospective analysis, we meticulously examined clinicopathologic data from a cohort of 90 patients who underwent LEEP at our institution between 2020 and 2021. Subsequently, we conducted inquiries with the patients to ascertain the degree of vaginal bleeding experienced during the postoperative periods of 3 and 6 weeks, comparing it to their preoperative menstrual flow. The magnitude of the menstrual volume alteration was then quantified using a menstrual volume multiplier(MVM). The primary endpoints of our investigation were to assess the hemostatic effect of rbFGF by means of evaluating the MVM. Additionally, the secondary endpoints encompassed the assessment of treatment-related side effects of such as infection and dysmenorrhea. RESULTS: Our findings demonstrated a significant reduction in hemorrhage following cervical LEEP. Specifically, in the per-protocol analysis, the study group exhibited a statistically significantly decrease in MVM after 3 weeks (0 [0-0] vs. 1 [0-1], respectively; p < 0.001) and after 6 weeks (1 [1] vs. 2 [1-3], respectively; p < 0.001) of the procedure. No notable disparities were observed in the remaining outcomes between the two groups. Moreover, a logistic regression analysis was employed to explore the relationship between significant bleeding and rbFGF treatment (p < 0.001, OR = -2.47, 95% CI -4.07 ~-1.21), while controlling for confounding factors such as age, BMI, and surgical specimen. CONCLUSIONS: In conclusion, our study findings highlight that the application of recombinant bovine basic fibroblast growth factorcan effectively mitigate hemorrhage subsequent to cervical loop electrosurgical excision procedure.

Upscaling cervical cancer screening and treatment for women living with HIV at a rural referral hospital in Tanzania: protocol of a before-and-after study exploring HPV testing and novel diagnostics.

BACKGROUND: Cervical cancer (CC) is nearly always caused by persistent human papillomavirus (HPV) infection. It is the most common cancer among women living with HIV (WLWH) and is the leading cause of cancer-related death in women in East Africa, with 10,241 new cases reported in Tanzania in 2020. In 2019, the World Health Organization (WHO) presented a global strategy for the elimination of CC as a public health problem, proposing targets to meet by 2030 for HPV vaccine coverage (90% of all 15-year-old girls), CC screening (70% of all women once at 35 and again at 45 years of age) and treatment delivery, to be scaled at national and subnational levels with a context-sensitive approach. This study aims to evaluate the upscaling of screening and treatment services at a rural referral hospital in Tanzania in order to address the second and third WHO targets. METHODS: This is an implementation study with a before-and-after design performed at St. Francis Referral Hospital (SFRH) in Ifakara (south-central Tanzania). CC screening and treatment services are integrated within the local HIV Care and Treatment Center (CTC). The standard of care, consisting of visualization of the cervix with acetic acid (VIA) and cryotherapy has been up-scaled with self-sampled HPV testing and also involved the introduction of mobile colposcopy, thermal ablation and loop electrosurgical excision procedure (LEEP). Participants are WLWH aged 18 to 65 years. Outcome measures included the percentage of women screened, HPV prevalence and genotype, and adherence to screening, treatment and follow-up plan. Additionally, we will explore the performance of novel diagnostic tests (QG-MPH®, Prevo-Check® and PT Monitor®), which share the features of being manageable and inexpensive, and thus a potential tool for effective triage in HPV high-prevalence cohorts. DISCUSSION: The study will provide relevant information about HPV prevalence and persistence, as well as reproductive and lifestyle indicators in a CC high-risk cohort of WLWH and about upscaling screening and treatment services at the level of a rural referral hospital in Tanzania. Furthermore, it will provide exploratory data on novel assays. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05256862, date of registration 25/02/2022. Retrospectively registered.

Risk factors for recurrence of cervical intraepithelial neoplasia after loop electrosurgical excisional procedure in patients with positive margins.

AIM: Loop electrosurgical excisional procedure (LEEP) is a major treatment method for cervical precancerous lesions. However, recurrence rates were estimated to be 15%, and the risk is increased if a surgical margin is involved by dysplastic cells. This study aimed to identify the risk factors for recurrence of cervical precancerous lesions in patients with positive margins. METHODS: We retrospectively reviewed medical records of patients who underwent LEEP between 2012 and 2014 and had a positive surgical margin. Clinicopathologic factors were collected, including age, parity, menopausal status, smoking, human papilloma virus infection, results of cytology/biopsy/LEEP, and specimen size and volume. RESULTS: A total of 117 patients with positive margins were included, and 26 (22.2%) patients had recurrence. According to a multivariate analysis, the recurrence rates were significantly higher in parous women (adjusted hazard ratio [HR], 2.92; 95% confidence interval [CI], 1.00-8.49), but positive margins at the exocervix (adjusted HR, 0.39; 95% CI, 0.17-0.91) and volume ≥4000 mm3 (adjusted HR, 0.36; 95% CI, 0.16-0.82) showed negative correlation. CONCLUSIONS: The risk of recurrence for cervical precancerous lesions increased in patients with a history of previous delivery, positive margin at the endocervix, and specimen volume of LEEP <4000 mm3 . These results could help gynecologists determine optimal treatment options for patients with positive margins.

Pregnancy outcome and risk of recurrence after tissue-preserving loop electrosurgical excision procedure (LEEP).

BACKGROUND/PURPOSE: This study aims to investigate whether women with cervical dysplasia after LEEP have an increased risk of pregnancy/childbirth complications or recurrence of dysplasia in an upcoming pregnancy. METHODS: Data from 240 women after LEEP were analysed retrospectively. The reference group consisted of 956 singleton births. Fisher's and Wilcoxon rank tests were used to detect differences between groups. Using logistic regressions, we analysed the effect of surgery-specific aspects of LEEP on pregnancy/childbirth complications and the frequency of CIN recurrences. RESULTS: We found that tissue-preserving LEEP did not lead to premature birth or miscarriage and did not increase the likelihood of CIN recurrence. We did not observe differences regarding preterm birth [< 37 (p < 0.28) < 34 (p < 0.31), < 32 weeks of gestation (p < 0.11)] or birth weight (< 2500 g (p < 0.54), < 2000 g (p < 0.77) between groups. However, women after LEEP exhibit a higher risk of premature rupture of membranes (PROM) at term (p < 0.009) and vaginal infections (p < 0.06). Neither volume nor depth of the removed tissue nor an additional endocervical resection seems to influence the likelihood of premature birth or early miscarriage. Performing an endocervical resection protects against CIN recurrence (OR 0.0881, p < 0.003). CONCLUSIONS: After tissue-preserving LEEP, there is an increased risk of vaginal infections and PROM at term in consecutive pregnancy. LEEP does not affect prematurity or miscarriage. The removal of additional endocervical tissue appears to be a protective factor against recurrence of CIN.

Spontaneous regression of cervical intraepithelial neoplasia 3 in women with a biopsy-cone interval of greater than 11 weeks.

BACKGROUND: Although there is broad consensus that only a subset of CIN3 will progress to cancer, there is currently no surefire way to predict which CIN3 will regress. Understanding the natural history of CIN3 is important, and finding markers for progression or regression could improve treatment strategies. According to the guidelines of the American Society for Colposcopy and Cervical Pathology of 2006, positive CIN3 p16 in women should be managed with excisional treatment (LEEP). For ethical reasons we cannot fail to treat women with CIN3 in order to study their regression capacity so we conducted a retrospective study to evaluate the regression rate of CIN3 diagnosed with a biopsy by studying the histological result of the cone removed by LEEP. We also investigated age, HPV genotypes and biopsy-cone interval distance as possible regression factors. METHODS: We selected 171 women with a histological diagnosis of positive CIN3 p16 as an entry criterion. All patients underwent LEEP / biopsy. A histological diagnosis of the cone of CIN3 or higher was considered as persistence or progression, the diagnosis of CIN1 or lower was considered as regression of the lesion. We used out a logistic model to study the probability of spontaneous regression of CIN3 as a function of the patient's age, the time elapsed between the biopsy and the cone (in weeks) and the HPV genotype. RESULTS: We found that the spontaneous regression rate of CIN3 was 15,8%, which was strongly associated with the biopsy-cone interval > 11 weeks. Genotype 16, the most represented, was present both in cases of regression (77.8%) and in persistence (83.3%). Regarding age, the estimated odds ratio of the probability of observing a regression in women over 25 years of age was 0.0045 times that of women under 25 years of age (CI: 0.00020, 0.036). Neither age nor viral genotype are significant as predictors of regression. CONCLUSION: To wait at least 11 weeks from the biopsy before subjecting the woman to LEEP could prevent unnecessary LEEP procedures, considering also that from CIN3 to carcinoma it takes years before the neoplastic transformation takes place.

Clearance of HR-HPV within one year after focused ultrasound or loop electrosurgical excision procedure in patients with HSIL under 30.

OBJECTIVE: To compare the clearance rate of high-risk human papillomavirus (HR-HPV) in patients with a high-grade squamous intraepithelial lesion (HSIL) 12 months after focused ultrasound (FUS) or loop electrosurgical excision procedure (LEEP), and analyze the influencing factors. METHODS: A retrospective cohort was established in HSIL patients with HR-HPV infection treated with FUS or LEEP from 2015 to 2019. The cohort consisted of 321 patients under 30 years of age, of which 119 patients received FUS and 202 patients received LEEP. The Cox regression model was used to identify the influencing factors for HR-HPV clearance. Kaplan-Meier method was applied to estimate the efficacy of FUS and LEEP in HR-HPV clearance, and the log-rank test was used to compare the efficacy difference between FUS and LEEP. RESULTS: Multivariate Cox regression analysis showed that both FUS and LEEP were independent influencing factors for HR-HPV clearance. HR-HPV cleared faster in the FUS group than in the LEEP group [the median time to HR-HPV clearance: 6 months in the FUS group (95% CI: 5.492-6.508) and 6 months in the LEEP group (95% CI: 5.734-6.266), p = 0.021]. The HR-HPV clearance rates at 6 and 12 months were 54.6% and 94.1% respectively in the FUS group, and 50.5% and 79. 2%, respectively in the LEEP group (p = 0.001 at 6 months, p = 0.000 at 12 months). CONCLUSIONS: For HPV-positive HSIL patients under 30, FUS had a better HR-HPV clearance effect than LEEP 1 year after treatment. FUS may be a viable modality for the treatment of young HSIL patients.

Video colposcopy versus headlight for large loop excision of the transformation zone (LLETZ): a randomised trial.

PURPOSE: To compare resected cone mass and resection margin status when performing Large Loop Excision of the Transformation Zone (LLETZ) using video colposcopy (LLETZ-VC) versus a headlight (LLETZ-HL) in women with cervical dysplasia. METHODS: Prospective, randomised trial (monocentric) at a specialised cervical dysplasia unit in a University Hospital. Women with a biopsy-proven CIN2 + or persisting CIN1 or diagnostic LLETZ were recruited and randomised. LLETZ was performed either under video colposcopic vision or using a standard surgical headlight. The primary endpoint was resected cone mass. Secondary endpoints were the rate of involved margins, fragmentation of the specimen, procedure time, time to complete haemostasis (TCH), blood loss, pain, intra- and postoperative complications, and surgeon preference. RESULTS: LLETZ-VC and LLETZ-HL (109 women each) had comparable cone masses (1.57 [0.98-2.37] vs. 1.67 [1.15-2.46] grams; P = 0.454). TCH was significantly shorter in the LLETZ-VC arm (60 [41-95.2] vs. 90 [47.2-130.2] seconds; P = 0.008). There was no statistically significant difference in involved resection margins (6/87 [6.5%] vs. 16/101 [13.7%], P = 0.068) and postoperative complications (13/82 [13.7%] vs. 22/72 [23.4%], P = 0.085). Patient-reported outcomes favoured LLETZ-VC with a lower use of analgesics (6/80 [7.0%] vs. 17/87 [16.3%]; P = 0.049). However, LLETZ-VC was more difficult to perform with significantly lower ratings for handling (7 [5-9] vs. 9 [8-10]; P < 0.001) and general satisfaction (7.5 [5-9] vs. 10 [8-10]; P < 0.001). CONCLUSION: Intraoperative video colposcopy for LLETZ has minimal benefits at the cost of surgeons' satisfaction. CLINICAL TRIAL REGISTRATION: NCT04326049 (ClinicalTrials.gov).

Identifying risk factors for post-operative bleeding in women undergoing loop electrosurgical excision procedure for cervical dysplasia.

BACKGROUND: Loop electrosurgical excision is a procedure utilised in the treatment of high-grade squamous intraepithelial lesion (HSIL) of the cervix. Post-operatively women may experience immediate and/or delayed per vaginal bleeding. AIMS: The objective of this prospective pilot study was to assess the feasibility of identifying and quantifying patients' subjective experiences of post-operative bleeding following a loop electrosurgical excision procedure (LEEP) for HSIL. In addition, an analysis of demographical, lifestyle and surgical factors was undertaken to assess for any statistically significant correlation with post-operative bleeding. MATERIALS AND METHODS: This study included 110 patients who underwent a LEEP for biopsy-proven or suspected HSIL between 2017 and 2020. Subjective data were collected from weekly post-operative surveys and correlated with procedural data. Primary outcome assessed was the subjective rate of bleeding experienced. Baseline demographics were age, body mass index (BMI), specimen size, human papilloma virus variant and histopathology. Other variables of interest collected were exercise intensity, and alcohol intake. RESULTS: No association of statistical significance was discovered between age, BMI, or day of menstrual cycle. There was a statistically significant association between exercise intensity or specimen size (greater than the median) and increased bleeding, primarily in the first 2 weeks. CONCLUSIONS: Women who undergo intense or prolonged exercise in the post-operative period may experience heavier bleeding particularly in the first 2 weeks post-LEEP. Heavy bleeding was also associated with a larger specimen size. There was no correlation between BMI, age or any other demographical factor.

Patient expectations and experiences with loop electrosurgical excision procedure in inpatient and outpatient settings.

BACKGROUND: Loop electrosurgical excision procedure (LEEP) for high-grade squamous intraepithelial lesion is performed in both an inpatient setting under general anaesthesia and an outpatient setting under local anaesthesia. Efficacy and safety are comparable and outpatient LEEP may save time and cost in the Australian setting. AIMS: We aim to compare patient satisfaction with inpatient LEEP compared to outpatient LEEP for Australian best practice. MATERIALS AND METHODS: This was a prospective quantitative and qualitative cohort study. An online questionnaire was sent to patients undergoing inpatient and outpatient LEEP to assess satisfaction with the procedure. Further histopathological and demographic data were also collected from the medical records. Groups were compared using Fischer's exact test and pain scores were compared using non-parametric tests. RESULTS: Ninety-three outpatients and 52 inpatients responded to the survey. No difference was found between groups with regard to rate of positive histopathological margins or number of passes required. Outpatients found the procedure to be more convenient than inpatients (P = 0.007), and experienced more pain during the procedure than the inpatient group (P < 0.001). There was no significant difference in pain scores following the procedure or post-procedure anxiety. CONCLUSIONS: Outpatient LEEP is an acceptable and well-tolerated procedure, comparable to inpatient LEEP. Regardless of the option chosen, patients are highly likely to be satisfied with their choice. Increased efforts should be made to reduce pre-procedural anxiety, which may in turn reduce expectations and experiences of pain.

Human Papillomavirus Vaccination Prior to Loop Electroexcision Procedure Does Not Prevent Recurrent Cervical High-grade Squamous Intraepithelial Lesions in Women Living With Human Immunodeficiency Virus: A Randomized, Double-blind, Placebo-controlled Trial.

BACKGROUND: Women living with human immunodeficiency virus (HIV), especially in sub-Saharan Africa, are at high risk for cervical high-grade squamous intraepithelial lesions (HSIL) and cervical cancer. These women have high HSIL recurrence rates after loop electroexcision procedure (LEEP). Retrospective studies suggest that human papillomavirus (HPV) vaccination improves response to treatment of cervical HSIL. METHODS: We performed a double-blind, randomized clinical trial enrolling 180 women living with HIV in Johannesburg, South Africa, diagnosed with cervical HSIL by colposcopic biopsy. Women received quadrivalent HPV vaccine or placebo (1:1) at entry, week 4, and week 26. LEEP was performed at week 4. Colposcopic-directed biopsies and cervical cytology were performed at weeks 26 and 52. The primary endpoint, cervical HSIL by histology or cytology at either week 26 or 52, was compared between arms using χ 2 analysis. RESULTS: Participant characteristics included median age of 39 years and median CD4 count 489 cells/µL, and 94% had HIV suppression. One hundred seventy-four women completed the vaccine/placebo series and had evaluable results at week 26 or 52. The proportion experiencing the primary endpoint was similar in the vaccine and placebo groups (53% vs 45%; relative risk, 1.18 [95% confidence interval, .87-1.6]; P = .29). HSIL recurrence was associated with a LEEP biopsy result of HSIL and detection of HSIL at the margins of the LEEP sample. CONCLUSIONS: This study did not support HPV vaccination to prevent recurrent HSIL after LEEP in women living with HIV. Recurrent HSIL was high despite virologic suppression. Improved treatments are needed for HSIL to reduce the burden of cervical cancer among women living with HIV. CLINICAL TRIALS REGISTRATION: NCT01928225.

Chemical composition of surgical smoke produced during the loop electrosurgical excision procedure when treating cervical intraepithelial neoplasia.

BACKGROUND: As LEEP (loop electrosurgical excision procedure) is being increasingly used for the diagnosis and treatment of uterine cervical intraepithelial neoplasia, surgical smoke during LEEP has become an inevitable health issue. Therefore, in this study, exposure to the chemical substances in surgical smoke produced during LEEP was assessed. METHODS: Smoke samples from patients with high-grade cervical intraepithelial neoplasia undergoing LEEP were collected by smoke-absorbing devices situated 1 m away from the operating table and near the nose of the operator during LEEP. Each plume sample was collected after 5 patients underwent LEEP, requiring 5 min for smoke collection for each patient. The chemicals of exposure to surgical smoke were assessed, and the hazard classes of these chemical components were evaluated by the International Agency for Research on Cancer. RESULTS: Qualitative analysis of the smoke produced during LEEP revealed a variety of potentially toxic chemicals under standard detection, such as benzene, toluene, xylene, ethylbenzene, styrene, butyl acetate, acrylonitrile, 1,2-dichloroethane, phenol, chlorine, cyanide, hydrogen cyanide and carbon monoxide. Additionally, the average concentration of carbon dioxide was 0.098 ± 0.015% during surgery and was higher than that before surgery (0.072 ± 0.007%, P < 0.001), and the concentration of formaldehyde was significantly higher during surgery (0.023 ± 0.009 mg/m3, P < 0.05) than before surgery (0.012 ± 0.001 mg/m3, P < 0.05). CONCLUSIONS: Most of the detected chemical concentrations in smoke generated during LEEP were below the exposure limits when local exhaust ventilation procedures were efficiently used. However, the concentrations of carbon dioxide and formaldehyde found in smoke were significantly higher after surgery. Wearing a high-filtration mask and using evacuation devices routinely and consistently when performing LEEP are recommended to protect perioperative personnel.

Adjuvant VACcination against HPV in surgical treatment of Cervical Intra-epithelial Neoplasia (VACCIN study) a study protocol for a randomised controlled trial.

BACKGROUND: Cervical cancer is caused by Human Papilloma viruses (HPV) and is preceded by precursor stages: Cervical Intraepithelial Neoplasia (CIN). CIN is mostly found in women in their reproductive age and treated with a Loop Electrosurgical Excision Procedure (LEEP). The recurrence or residual disease rate after treatment is up to 17%. These women have a lifelong increased risk of recurrent CIN, cervical cancer and other HPV related malignancies. Furthermore, LEEP treatments are associated with complications such as premature birth. Limited data show that prophylactic HPV vaccination at the time of LEEP reduces recurrence rates, therefore leading to a reduction in repeated surgical interventions and side effect like preterm birth. The primary study objective is to evaluate the efficacy of the nonavalent HPV vaccination in women with a CIN II-III (high-grade squamous intraepithelial lesion (HSIL) lesion who will undergo a LEEP in preventing recurrent CIN II-III after 24 months. METHODS: This study is a randomised, double blinded, placebo controlled trial in 750 patients without prior HPV vaccination or prior treatment for CIN and with histologically proven CIN II-III (independent of their hrHPV status) for whom a LEEP is planned. Included patients will be randomised to receive either three injections with nonavalent (9 HPV types) HPV vaccine or placebo injections (NaCL 0.9%) as a comparator. Treatment and follow-up will be according the current Dutch guidelines. Primary outcome is recurrence of a CIN II or CIN III lesion at 24 months. A normal PAP smear with negative hrHPV test serves as surrogate for absence of CIN. At the start and throughout the study HPV typing, quality of life and cost effectiveness will be tested. DISCUSSION: Although prophylactic HPV vaccines are highly effective, little is known about the effectivity of HPV vaccines on women with CIN. Multiple LEEP treatments are associated with complications. We would like to evaluate the efficacy of HPV vaccination in addition to LEEP treatment to prevent residual or recurrent cervical dysplasia and decrease risks of repeated surgical treatment. TRIAL REGISTRATION: Medical Ethical Committee approval number: NL66775.078.18. Affiliation: Erasmus Medical Centre. Dutch trial register: NL 7938. Date of registration 2019-08-05.

Recurrence rate after loop electrosurgical excision procedure (LEEP) and laser Conization: A 5-year follow-up study.

OBJECTIVE: Conization aims to remove pre-neoplastic lesions of the uterine cervix. Several techniques for conization have been compared, but evidence regarding the most effective therapeutic option is scant. Here, we aimed to compare the recurrence rate following laser conization and loop electrosurgical excision procedure (LEEP) in patients with high-grade cervical dysplasia (HSIL/CIN2+). METHODS: This is a retrospective multi-institutional study. Medical records of consecutive patients with HSIL/CIN2+ undergoing conization between 2010 and 2014 were retrieved. A propensity-score matching (PSM) was applied in order to reduce allocation bias. The risk of developing recurrence was estimated using Kaplan-Meir and Cox hazard models. RESULTS: Overall, 2966 patients had conization over the study period, including 567 (20%) and 2399 (80%) patients having laser conization and LEEP, respectively. Looking at predictors of recurrence, diagnosis of CIN3 (HR:3.80 (95%CI:2.01,7.21); p < 0.001) and HPV persistence (HR:1.81 (95%CI:1.11,2.96); p < 0.001) correlated with an increased risk of recurrence. After applying a PSM we selected 500 patients undergoing laser conization and 1000 undergoing LEEP. Patients undergoing LEEP were at higher risk of having positive surgical margins in comparison to patients undergoing laser conization (11.2% vs. 4.2%). The risk of having persistence of HPV was similar between the two groups (15.0% vs. 11.6%;p = 0.256). Five-year recurrence rate was 8.1% and 4% after LEEP and laser conization, respectively (p = 0.023). HPV persistence was the only factor associated with [5-]year recurrence after both laser conization (p = 0.003) and LEEP (p = 0.001). CONCLUSIONS: HPV persistence is the only factor associated with an increased risk of recurrence after either laser conization or LEEP. Owing to the lack of data regarding obstetrical outcomes, we are not able to assess the best therapeutic option for women with cervical dysplasia.

Conservative management of CIN2 p16 positive lesions in women with multiple HPV infection.

BACKGROUND: According to the 2006 American Society for Colposcopy and Cervical Pathology guidelines, positive CIN2 p16 in women over the age of 25 should be managed with excisional treatment. However, excisional treatment is associated with physical, psychological and obstetric morbidity and can have a negative impact on sexual function. In our study we sought to identify a clear management strategy, addressing the impact of routine use of p16 immunohistochemistry in this population and identify appropriate criteria for patient selection with the aim of reducing over-treatment. METHOD: We studied the medical records of 130 patients who had undergone laser therapy for CIN2. Each patient underwent colposcopy, biopsy and HPV test and were tested for p16 protein,. Patients were divided based on HPV infection into: single infections, multiple infections. All patients underwent ZTA laser therapy with follow-up (2-year follow-up). STATISTICAL ANALYSIS: Contingency tables were created to evaluate the correlation between single, multiple and CIN2+ infections. Values with p < 0.05 were considered statistically significant. RESULTS: Single infections had a histological regression of 61.8% (21/34) and a histological persistence rate of 35.3% (12/34), which was greater than the multiple infection rate. The common characteristic that the women with persistence and progression had was the dimension of the lesion and the genotype 16. Ten cases of histological persistence and the only case of progression had one lesion greater than three quarters of the cervix. CONCLUSIONS: With the progress of our understanding of the natural history of infection from human papillomavirus and the increasing use of colposcopy, thanks to the addition of HPV genotyping and the technique of immunohistochemistry, conservative management of these lesions is now possible.

Defining the short-term disease recurrence after loop electrosurgical excision procedure (LEEP).

BACKGROUND: The goal of cervical cancer screening is to identify dysplastic lesions for subsequent excision in order to prevent invasive disease. There is clinical equipoise, on how to best follow women for disease surveillance after treatment with some Canadian provinces exclusively performing colposcopy and some utilizing Human Papilloma Virus (HPV) testing in addition to cervical cytology. Loop Electrosurgical Excision Procedure (LEEP) is used to treat pre-invasive HPV-mediated disease and patients are typically followed for 12 months after disease excision. This study aims to quantify the prevalence of high-grade disease at the time of the second follow-up colposcopy visit, in a practice setting that utilizes laser ablation in addition to LEEP. METHODS: In a retrospective cohort study, consecutive patient charts were accessed through the electronic medical record system, ARIA, at the Tom Baker Cancer Centre, in Calgary, Alberta, from January 2010 to December 2015. Data was extracted and a REDCap database was used to compile pertinent information from charts meeting inclusion criteria. Descriptive and analytic statistics were performed. RESULTS: Of the 303 patients identified, 221 patients met inclusion criteria. 86% of these patients met discharge criteria from colposcopy after the second follow up visit. 31 (14%) were seen in a subsequent visit for abnormal findings. Of these, 7 (3.2%) underwent further treatment for high-grade disease/Cervical Intraepithelial Neoplasia (CIN 2/3). Of the 31, 23 (10.6%) had a third - negative - visit, resulting in discharge from colposcopy. One patient had a repeat LEEP for persistent Low-Grade Squamous Intraepithelial Lesion (LSIL). CONCLUSION: In summary, our data demonstrates a prevalence of 3.2% of high-grade disease at the time of a second colposcopic follow up visit after treatment, in a setting which frequently utilizes laser ablation in combination with LEEP, for large lesions. This recurrence rate is consistent with most published literature on recurrence rates of CIN2/3.

A standardized simulation training program to type 1 loop electrosurgical excision of the transformation zone: a prospective observational study.

PURPOSE: To evaluate a simulation-based standardized training program for type 1 loop electrosurgical excision procedure (LEEP) under direct colposcopic vision in postgraduate teaching. METHODS: Seventeen participants (five experienced and 12 novice surgeons) performed 170 simulated cervical excisional procedures. Each participant performed 10 type 1 (cone length between 8 and 10 mm) excisional procedures under direct colposcopic vision on a low-fidelity simulator. Length of specimen was measured after each excision allowing the surgeons a subsequent resection to ensure a cone length of more than 8 mm. Main outcome measures were cone length, specimen fragmentation, and a self-developed score (LEEP score), which allowed the simultaneous evaluation of both measured parameters. RESULTS: The precision of the excision showed statistically significant improvement in the novice group during the training procedures after five procedures [LEEP score 1.61 (SD 1.34) vs. 0.46 (SD 0.58); p = 0.023], while experts showed consistently high performance. Inexperienced surgeons performed more frequently cuts that were too deep than experienced surgeons (33/120, 27.5% vs. 4/50, 8%; p = 0.003). CONCLUSIONS: Low-fidelity simulation training seems to be an effective method for learning the accurate cone length for a type 1 excision for novice surgeons. As excessive excisions are related with high risk for premature delivery in subsequent pregnancies, in our opinion, LEEP should be practiced in simulation training, especially before performing in woman of reproductive age.

Can we predict surgical margin positivity while performing cervical excisional procedures?

We designed this study to evaluate any factors associated with positive surgical margin in conisation specimens and to determine the optimal cone size. The medical records of patients who had undergone a loop electrosurgical excision procedure (LEEP), cold-knife conisation (CKC) and needle excision of the transformation zone (NETZ) procedure were reviewed retrospectively. Two hundred and sixty eight women fulfilled the inclusion criteria. Univariate analyses showed that 'postmenopause', 'HSIL on smear', 'previous colposcopic examination revealing HSIL in endocervical curettage (ECC) material and in two or more ectocervical quadrants' and 'managing with LEEP' were significant predictors of surgical margin positivity. Nulliparous patients showed significantly lower rate of surgical margin positivity. 'Postmenopause', 'previous colposcopic examination revealing HSIL in ECC material and in two or more ectocervical quadrants' and 'HSIL on smear' were identified as independent predictors of surgical margin positivity according to multivariate analyses.IMPACT STATEMENTWhat is already known on this subject? Previous studies demonstrated 'menopause', 'Age ≥50', 'managing with LEEP', 'disease involving >2/3 of cervix at visual inspection', 'training level of the surgeon', 'cytology squamous cell carcinoma' and 'mean cone height' as factors associated with positive surgical margin in conisation specimens.What do the results of this study add? In our study, univariate analyses showed that 'postmenopause', 'HSIL on smear', 'previous colposcopic examination revealing HSIL in endocervical curettage material and in two or more ectocervical quadrants' and 'managing with LEEP' were associated with surgical margin positivity. On the other hand, nulliparous women showed significantly lower rate of surgical margin positivity compared with parous women. Multivariate analyses showed that 'postmenopause', 'previous colposcopic examination revealing HSIL in endocervical curettage material and in two or more ectocervical quadrants' and 'HSIL on smear' were independent predictors of surgical margin positivity in conisation specimens.What are the implications of these findings for clinical practice and/or further research? We can predict high-risk patients with regard to surgical margin positivity. Prediction of high-risk patients and management with a tailored approach may help minimise surgical margin positivity rates.

HPV16 persistent infection and recurrent disease after LEEP.

BACKGROUND: About 23% of patients develop CIN2+ after LEEP treatment due to residual or recurrent lesions. The majority of patients with HPV infection were HPV negative before treatment, but 16,4% were still HPV 16 positive after treatment, indicating that conization do not necessarily clear HPV infection rapidly. The aim of this retrospective study was to evaluate the possible correlation existing between the appearance of recurring high-grade lesions and the viral genotype 16, and other risk factors such as residual disease. METHODS: One hundred eighty-two HPV positive patients underwent LEEP for CIN2+. The follow-up post treatment was carried out every 6 months. Abnormal results during follow-up were confirmed histologically and considered recurrent high-grade intraepithelial cervical lesions (CIN2/CIN3 or CIS). Statistical analysis was performed by using the SPSS software package for Windows (version 15.0, SPSS, Chicago, IL, USA). Descriptive statistics are expressed as frequency, arithmetic mean, standard deviation (S.D.) and percentages. We calculated significance (P < 0.5) with the Easy Fischer Test. We calculated the Odds Ratio (OR) of women with peristent HPV 16 infection and positive margin, to have a recurrence. RESULTS: In our study, the rate of persistent infection from HPV 16, after LEEP, was 15.9% (29/182) with 94% (17/18) of the recurring disease occurring within 18 months of follow up. From this study it was found that the persistence of genotype 16 is associated with a greater rate of relapse post-conization of CIN 2+ lesions, with respect to other genotypes. Our study further supports those studies that demonstrate that the risk for residual disease or relapse is not to be overlooked, also when the margins are negative, but persistent HPV infection is present. In our case study, 40% of relapses were in women with negative margin, but with persistent HPV 16 infection. Even more so, the margins involved in HPV16 positive subjects is another prediction factor for relapse. CONCLUSIONS: Our results show the importance of genotyping and that persistent HPV 16 infection should be considered a risk factor for the development of residual/recurrent CIN 2/3.