HPV E6/E7 mRNA combined with thin-prep cytology test for the diagnosis of residual/recurrence after loop electrosurgical excision procedure in patients with cervical intraepithelial neoplasia.

To evaluate the diagnostic value of combining HPV E6/E7 mRNA testing with Thin-Prep cytology (TCT) for residual/recurrence detection, a total of 289 patients who underwent loop electrosurgical excision procedure (LEEP) for high-grade cervical lesions were included. Patients were followed up at different time points, and residual/recurrent lesions were confirmed through vaginoscopy. TCT, HPV-DNA, and HPV E6/E7 mRNA tests were conducted. Diagnostic performance, including sensitivity, specificity, positive predictive value, negative predictive value, and accuracy, was assessed. Among the patients, 76 cases showed residual lesions/recurrence, while 213 cases showed no residual/recurrence. Positive margins in the cervical-vaginal and cervical canal areas were associated with a higher risk of residual/recurrence. The combined HPV E6/E7 mRNA and TCT test showed higher diagnostic efficacy than individual tests at 6-, 12-, and 24-months follow-up. The combined test consistently demonstrated higher specificity and sensitivity, with significantly larger area under the curve (AUC) values compared to the individual tests.

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.

Evaluating a novel 3D printed model for simulating Large Loop Excision of the Transformation Zone (LLETZ).

BACKGROUND: Electrosurgical excisions are common procedures for treating cervical dysplasia and are often seen as minor surgeries. Yet, thorough training of this intervention is required, as there are considerable consequences of inadequate resections, e.g. preterm birth, the risk of recurrence, injuries and many more. Unfortunately, there is a lack of sufficiently validated possibilities of simulating electrosurgeries, which focus on high fidelity and patient safety. METHODS: A novel 3D printed simulator for examination and electrosurgical treatment of dysplastic areas of the cervix was compared with a conventional simulator. Sixty medical students experienced a seminar about cervical dysplasia. Group A underwent the seminar with the conventional and Group B with the novel simulator. After a theoretical introduction, the students were randomly assigned by picking a ticket from a box and went on to perform the hands-on training with their respective simulator. Each student first obtained colposcopic examination training. Then he or she performed five electrosurgical excisions (each). This was assessed with a validated score, to visualize their learning curve. Furthermore, adequate and inadequate resections and contacts between electrosurgical loop and vagina or speculum were counted. Both groups also assessed the seminar and their simulator with 18 questions (Likert-scales, 1-10, 1 = strongly agree / very good, 10 = strongly disagree / very bad). Group B additionally assessed the novel simulator with four questions (similar Likert-scales, 1-10). RESULTS: Nine of 18 questions showed statistically significant differences favoring Group B (p < 0.05). Group B also achieved more adequate R0-resections and less contacts between electrosurgical loop and vagina or speculum. The learning curves of the performed resections favored the novel simulator of Group B without statistically significant differences. The four questions focusing on certain aspects of the novel simulator indicate high appreciation of the students with a mean score of 1.6 points. CONCLUSION: The presented novel simulator shows several advantages compared to the existing model. Thus, novice gynecologists can be supported with a higher quality of simulation to improve their training and thereby patient safety.

Management of Cervical Dysplasia Using Office Loop Electrosurgical Excision Procedure.

Declining cervical cancer rates in the United States highlights the value of prevention and early detection of premalignant cervical disease afforded by the human papillomavirus vaccine and Pap smear. The availability of in-office loop electrosurgical excision procedure affords clinicians with a cost-effective and preferred tool for the excision of high-grade lesions of the cervix with minimal risk for severe adverse outcomes. The most recent American Society for Colposcopy and Cervical Pathology guidelines recommend a risk-based approach for the detection, treatment, and surveillance of cervical disease and specifically focus on the risk of developing cervical intraepithelial neoplasia 3 or worse histology.

Negative loop electrosurgical excision procedure (LEEP) following cervical biopsy diagnosis of high grade squamous intraepithelial lesion.

CONTEXT: Loop Electrosurgical Excision Procedure (LEEP) is commonly performed after cervical biopsy diagnosis of high grade squamous intraepithelial lesion (HSIL/CIN2 or CIN 3). Histological and immunohistochemical assessments are made to differentiate reactive and metaplastic changes from dysplastic changes. A Human Papillomavirus (HPV) test is used for prognostic assessment after conization. OBJECTIVE: We retrospectively reviewed cases where the cervical biopsy showed HSIL but the LEEP specimen was negative for high grade dysplasia. Our aim was to determine the cause of miscorrelation. DATA: IRB approval was obtained and a search was made of all LEEP specimens received during 2018. We reviewed 25 of 137 LEEP specimens that did not correlate with the diagnosis of HSIL rendered on the cervical biopsy. These were from women between 25 to 54 years. All cases had positive high-risk HPV with 80% being non16/18 subtype. On review, 8/25 had HSIL with the remainder of cases falling short of HSIL diagnosis. Follow up cytology with HPV test after the LEEP procedure was negative in all but one case of LSIL with persistent non-16/18 HPV. CONCLUSION: The study highlights the diagnostic difficulties of distinguishing HSIL from immature squamous metaplasia. The practical implication is that in cases with non-16/18 high risk HPV which have thin epithelium and fall short of definite morphologic criteria of HSIL, presence of immature squamous metaplasia should be carefully evaluated. The specific role of CK7 and CK17 which highlight squamocolumnar junctional cells and metaplastic cells, respectively, needs to be explored in these cases.

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.

Adenocarcinoma cervical in situ: abordagem na atenção primária e secundária à saúde / Cervical adenocarcinoma in situ: approach in primary and secondary health care

O adenocarcinoma cervical in situ é uma doença rara, totalmente curável, diagnosticada predominantemente por meio de rastreamento cervicouterino seguido de biópsia guiada por colposcopia e/ou conização. O tratamento em pacientes que desejam preservar a fertilidade pode ser realizado num contexto ambulatorial; aquelas com paridade definida deverão ser abordadas em nível terciário.(AU)

Cervical adenocarcinoma in situ is a rare, fully curable disease diagnosed predominantly through cervical-uterine screening followed by colposcopy-guided biopsy and/or conization. Treatment in patients wishing to preserve fertility may be performed in an outpatient setting; those with defined parity should be approached at the tertiary level.(AU)

A comparison study of post-operative infection analysis of cold-knife conization and loop electrosurgical excision procedure for cervical high-grade squamous intraepithelial lesion.

BACKGROUND: High-grade squamous intraepithelial lesion (HSIL) is a premalignant condition of the cervical cancer. Loop electrosurgical excision procedure (LEEP) and cold-knife conization (CKC) were the most effective treatment. Most studies focused on the recurrence rate, positive margin rate, residual disease rate, secondary hemorrhage or cervical stenosis of these two methods. At present, there are few researches about the post-operative infection comparing LEEP with CKC for treating HSIL. METHODS: One hundred and fourteen patients diagnosed as HSIL were underwent cold conization (n=43) or LEEP (n=71), according to 1:2 matching approximately and being divided randomly into two groups. The information, including the post-operational inflammatory complications, the leucorrhea abnormalities, the pathogens isolated from cervical secretions and pathological reports, were collected for comparison. RESULTS: There was no significant difference between them in bleeding, diameter, depth or volume of tissue between two groups. However, the operation time of the CKC group (24.81±11.09) minutes was longer than that of LEEP group (15.79±9.82) minutes. Seventeen patients of the LEEP group were admitted postoperatively as emergencies for secondary-hemorrhage. But it did not happen in CKC group. During the follow-up period, 28 patients (CKC 8 vs. LEEP 20) were diagnosis as reproductive tract infections. Fourteen patients (CKC 6 vs. LEEP 8) had leucorrhea abnormalities. Eighteen patient (CKC 3 vs. LEEP 15) isolated pathogens from their cervical secretions. There was no significant correlation between leucorrhea abnormality and cervical secretion abnormality. The positive rate of cervical secretion infection in the LEEP group was higher than the CKC group (P<0.05). The inflammatory response and process had some pathological difference in post-operation time of two groups, especially in those secondary hemorrhage cases. CONCLUSIONS: These two excision procedures for treating HSIL have their respective advantages and disadvantages. This study indicates that the incidence of persistent cervical infection after the CKC operation with Sturmdorf suturing is lower than that of after LEEP surgery. Clinicians should pay attention to the pathogen isolated from cervical post-operative secretion. It is conducive to find hidden pathogens and control subsequent surgical inflammation.

Residual lesions in uterine specimens after loop electrosurgical excision procedure in patients with CIN.

OBJECTIVE: To identify the risk factors for residual lesion in hysterectomy specimens after loop electrosurgical excision procedure (LEEP) for cervical intraepithelial neoplasia (CIN). METHODS AND RESULTS: We retrospectively analyzed the clinical data of 594 patients who underwent total hysterectomy after LEEP for CIN at the International Peace Maternity and Child Health Hospital affiliated to Shanghai Jiaotong University between July 2006 and June 2015. Among the 594 patients, there were no residual lesions in uterine specimens of 409 (68.9%) patients; residual CIN1 was found in 24 (4%) patients, CIN2 and CIN3 in 142 (23.9%) patients, and cervical cancer in 19 (3.2%) patients. On univariate analysis age, menopausal status, margin involvement, lesion grade, abnormal endocervical curettage (ECC) result, and persistent human papillomavirus (HPV) infection post operation were significantly associated with residual lesions after LEEP (P < 0.05). Multivariate regression analysis using the logistic regression model showed abnormal ECC result and persistent HPV positivity to be independent risk factors for residual lesions after LEEP. LEEP with positive margins and persistent HPV infection were also associated with high risk of invasive cervical cancer in CIN2+ patients. CONCLUSIONS: Abnormal ECC result and post-treatment HPV infection are predictors of residual lesion after LEEP. In combination, they could be useful for risk stratification and selection of the management approach. Postmenopausal CIN2+ patients with positive margins and persistent postoperative HPV infection may have high risk of cervical invasive cancer.

El método CONO-UC: un protocolo integrado de toma de decisión y manejo de lesiones pre-invasoras del cuello uterino útil para especialistas jóvenes / The CONO-UC method: an integrated protocol for decision-making and management of pre-invasive cervical lesions useful for young specialists

OBJETIVOS: En la actualidad, existe una alta tasa de sobre-tratamiento de lesiones precursoras cervicales, la cual, en su causalidad, depende de la inexperiencia del operador que toma las decisiones. El objetivo del presente trabajo fue desarrollar un método estandarizado de ponderación/juicio de variables diagnósticas y tratamiento útiles de ser usadas por especialistas jóvenes a fin de minimizar el riesgo de manejo inadecuado. MATERIALES Y MÉTODOS: Se incluyeron 471 pacientes referidos por citología anormal y tratados mediante asa de LEEP. Se calcularon la sensibilidad, la especificidad, los valores predictivos y las relaciones de probabilidad para el diagnóstico de NIE2+ para cada uno de los métodos de diagnóstico. A cada residente se le enseñó un protocolo estandarizado de tratamiento mediante asa. Una vez identificados los mejores predictores, se construyó una escala de puntaje que ponderaba las variables y se definió mediante curva ROC el major punto de corte para la predicción de NIE2+. Las diferencias entre los grupos se compararon mediante Chi-cuadrado, ANOVA o t-test. Se construyó curva de fallas mediante el método de 1-Kaplan Meier. RESULTADOS: La prevalencia de NIE2+ en esta cohorte fue 66%. La concordancia entre las pruebas diagnósticas fue baja, teniendo la colposcopia el peor valor predictivo positivo y el mayor riesgo de sobre-tratamiento. Para la escala de puntaje se incluyeron la edad, la citología, la colposcopia (estratificación basada en la extensión de compromiso por cuadrantes), la biopsia por mascada y la concordancia entre pruebas diagnósticas. Un puntaje≥ 9 asociado al uso de un protocolo estandarizado, obtuvo tasas de sobre-tratamiento <15%, de recurrencias de NIE2+ <5% a 5 años y una baja tasa de procedimientos sub-óptimos o con complicaciones (<2 %). CONCLUSIONES: El método CONO-UC al combinar un sistema de puntaje integrado (punto de corte) con un protocolo estandarizado de excisión, permite minimizar el riesgo de sobretratamiento o tratamiento inadecuado, por parte de especialistas jóvenes, de lesiones preinvasoras del cuello uterino, reduciendo además el número de procedimientos indicados innecesariamente y manteniendo una alta tasa de éxito terapéutico.

GOALS: Currently, there is a high rate of over-treatment of precursor cervical lesions, which, in their causality, depends on the inexperience of the decision-making operator. The objective of the present study was to develop a standardized method of weighting / judgment of diagnostic variables and treatment useful to be used by young specialists in order to minimize the risk of improper handling. MATERIAL AND METHODS: We included 471 patients referred by abnormal cytology and treated by LEEP. Sensitivity, specificity, predictive values and likelihood ratios for the diagnosis of CIN2+ were calculated for each of the diagnostic methods. Each resident was taught a standardized protocol to carry out a LEEP procedure. Once the best predictors were identified, a scoring scale was constructed that weighted the variables and the best cut-off point for the prediction of CIN2+ was defined by ROC curve. Differences between groups were compared using Chi-square, ANOVA or t-test. Failure curves were built up using the 1-Kaplan Meier method. RESULTS: The prevalence of CIN2+ in this cohort was 66%. The agreement between the diagnostic tests was low, with colposcopy having the worst positive predictive value and the highest risk of over-treatment. Age, cytology, colposcopy (stratification based on the extent of compromise by quadrants), punch biopsy, and agreement between diagnostic tests were included for building the scoring scale. A score ≥ 9 in association with the use of a standardized protocol obtained rates of over-treatment <15%, recurrences of CIN2+ <5% at 5-year follow-up and a low rate of suboptimal procedures or complications (<2%). CONCLUSIONS: The UC-CONE method, by combining an integrated scoring system with a standardized excision protocol, minimizes the risk of over-treatment or inadequate treatment of pre-invasive cervical lesions by young specialists, reducing the number of procedures indicated unnecessarily and maintaining a high rate of therapeutic success.

Impact of anaesthesia mode on evaluation of LEEP specimen dimensions.

OBJECTIVES: To study the influence of anaesthesia (local by cervical block vs. general or spinal anaesthesia) on height and volume of resection specimens in case of conization treatment for cervical intraepithelial neoplasia (CIN). METHODS: Prospective observational study of all patients who underwent a first treatment by loop electrosurgical excision procedure (LEEP) for CIN. Height of fresh resection specimens was first measured by the operator and then by the pathologist after formaldehyde fixation. Volume of fresh specimens was measured in a measuring cylinder by fluid displacement. RESULTS: One hundred patients were included and 35% of LEEP were performed under local anaesthesia. There was a significant difference in height of specimens depending on anaesthesia mode: after fixation, the average height was 11.2mm in the general or spinal anaesthesia group vs. 8.8mm in the local anaesthesia group (P=0.002). There was also a difference in terms of volume depending on anaesthesia mode: 1.6mL in local anaesthesia group vs. 2.3mm in general and spinal anaesthesia group (P=0.01). CONCLUSIONS: Anaesthesia mode has an impact on height and volume of LEEP specimens. In our experience, local anaesthesia could reduce LEEP specimen height.

Risk factors for residual disease after cervical conization in patients with cervical intraepithelial neoplasia grades 2 and 3 and positive surgical margins.

OBJECTIVE: To evaluate risk factors for the persistence of cervical intraepithelial neoplasia (CIN) grade ≥2 following repeat surgical procedures in patients with CIN grades 2 and 3 and positive surgical margins. STUDY DESIGN: This study included patients with CIN grades 2 and 3 and positive surgical margins following loop electrosurgical excision procedures (LEEP), who had undergone additional surgery between 2007 and 2014. Factors associated with CIN grade ≥2 on biopsy results after the second operation were assessed by multiple logistic regression analysis. Factors considered included patient age, parity, menopausal status, smoking, referral cytology, initial LEEP pathology, time interval between LEEP and surgical procedures, presence of disease on endocervical sampling, endocervical surgical margins, glands, disease surrounding ≥50% of the cervical circumference and requirement for multiple sweeps on initial LEEP to excise a lesion. The forward likelihood ratio method was used and significance was set at p<0.05. RESULTS: Repeat surgical procedures were performed in 104 patients, 75 with CIN 2 and 29 with CIN 3, with 43 (41.3%) reported as normal or CIN 1. However, 57 (54.8%) patients had CIN ≥2 lesions and four (3.8%) had previously undiagnosed cervical cancer. Factors associated with CIN ≥2 lesions included requirement for multiple sweeps (vs. a single sweep; odds ratio [OR] 5.967; 95% confidence interval [CI] 2.183-16.311, p<0.001) and involvement of ≥50% of the cervical circumference (vs. <50%; OR 5.073; 95% CI 1.501-17.146, p=0.009). CONCLUSION: As lesions requiring multiple sweeps for excision and/or surrounding ≥50% of the cervical circumference during initial conization are associated with recurrent CIN ≥2 lesions, attention should be paid during resection to prevent margin positivity. If surgical margins are positive, however, repeat surgical procedures should be considered in patients with CIN 2 and CIN 3 lesions and these risk factors.

Association between human papillomavirus type 16 E6 and E7 variants with subsequent persistent infection and recurrence of cervical high-grade squamous intraepithelial lesion after conization.

The study aimed to detect the variants of human papillomavirus (HPV) type 16 E6 and E7 in patients with cervical high-grade squamous intraepithelial lesion (HSIL), and to determine the existence and recurrence of persistent infection after treatment with loop electrosurgical excision procedure (LEEP). Preoperatively collected cervical exfoliated cells from 100 HPV 16 positive HSIL patients enrolled in the study were used to test for E6 and E7 variants. Follow-ups which included TCT, HPV test, and colposcopy were performed every 3 months after the operation, and colposcopic biopsy and endocervical curettage were performed for patients with abnormalities. Patients were followed for 2 years, and recurrence was defined as detecting low-grade squamous intraepithelial lesion (LSIL) or relapse of HSIL in 1 year. In 81% of patients, the E6 variant was the Asian prototype (As.P), 14% of patients had the European variant, 2% had the European prototype (EP), and 3% had the African 1 variant (Af1). The HPV16 could be easily cleared by LEEP in patients with As.P. Persistent infection or recurrence was very rare in this group. The patients with European variants T350G or A442C had a significantly higher incidence of persistent and recurring HPV16 infection. In conclusion, (i) in most cases, As.P caused HSIL. (ii) The European variant E6 T350G/A442C may be associated with higher rates of recurring and persistent HPV16 infection after the LEEP. (iii) The E7 gene mutation may not be a risk factor for recurring HSIL caused by HPV16 or persistent infection. J. Med. Virol. 88:1982-1988, 2016. © 2016 Wiley Periodicals, Inc.

[Impact of the loop electrosurgical excision procedure for cervical dysplasia on sexual function]. / Impact de la conisation cervicale à l'anse diathermique sur la qualité de vie sexuelle.

OBJECTIVE: To assess the consequences of loop electrosurgical excision procedure (LEEP) on the quality of sexual life. MATERIAL AND METHODS: A prospective observational study in two university hospital departments in Marseille, France, including women requiring a LEEP. Sexual quality of life was assessed before LEEP and three months after the procedure with a self-administered validated questionnaire: the Brief Index of Sexual Functioning for Women (BISF-W). RESULTS: Among the 100 women included, 69 filled both questionnaires. Among the 69 women whose outcomes were available, composite BISF-W score was significantly lower before LEEP than three months after LEEP (28.3±13 vs 30.1±13.2; P=0.01). The items scores concerning desire (D1) and orgasm (D5) were significantly improved after LEEP (4.3±2.3 vs 5±2.2 [P<0.001] and 4.3±2.5 vs 4.7±2.6 [P<0.001]). CONCLUSIONS: This study found an improved quality of sexual life after LEEP. These findings suggest that the psychological impact of HPV infection on sexual function is greater than the anatomical and functional impact of LEEP.

HPV genotyping among women treated for high-grade cervical intraepithelial neoplasia with no lesion in the conization specimen.

OBJECTIVE: To evaluate whether specific HPV genotypes or multiple HPV infection are associated with absence of cervical intraepithelial neoplasia (CIN) in the conization specimen. METHODS: In a retrospective study, data were reviewed for women treated by conization at a center in Barcelona, Spain, between 2008 and 2011. Women whose pretreatment biopsy showed CIN2/3 with positive p16 staining but had no lesions in the conization specimen were included in the study group if material was sufficient for HPV genotyping. Age-matched control patients who had CIN2/3 in the conization specimen were selected. HPV genotyping was conducted on all histologic specimens. RESULTS: Both groups contained 43 patients. High-risk HPV genotypes were identified in the conization specimens of 14 (33%) women in the study group and of 42 (98%) in the control group (P<0.001). HPV16/HPV18 was detected in the pretreatment biopsy samples of 27 (63%) women in the study group and 25 (58%) in the control group (P=0.413). Multiple HPV infections were detected pretreatment in 8 (19%) women in the study group and 9 (21%) in the control group (P=0.50). CONCLUSION: No association was found between HPV genotype or multiple HPV infection and absence of lesion in the conization specimen.

Influence of a loop electrosurgical excision procedure (LEEP) on levels of cytokines in cervical secretions.

Over the past decade, there has been heightened interest in determining if there is an increased risk of adverse reproductive outcomes among women who had a loop electrosurgical excision procedure (LEEP) to remove cervical intraepithelial neoplasia (CIN). The objective of this exploratory study was to determine if the treatment of CIN with a LEEP is associated with changes in cervical soluble immune markers. Cervical cytokine concentrations were measured in women treated with LEEP and a control group of women who had colposcopy only and did not undergo LEEP. Cytokines were examined in cervical secretions collected in Merocel(®) sponges at study entry and at 6-month follow-up. Cytokines were measured using a Luminex 18-plex cytokine bead assay. The mean cytokine levels were not significantly changed from baseline to follow-up in either group, with the exception of TNF-α, which decreased among women who underwent a LEEP. When the mean levels of cytokines of the treated and untreated groups at baseline or follow-up were compared, cytokine levels tended to be lower in the treated group (particularly IFN-γ, IL-6, IL-8, and MCP-1). Findings from adjusted repeated measures analyses revealed no differences between the two groups with regard to changes in cytokine levels over time. Overall, women undergoing a LEEP showed few changes in the cervical microenvironment relative to untreated women. Future studies with additional cervical environment markers and larger sample sizes are needed to determine if a LEEP is associated with dysregulation of the cervical microenvironment.

Influence of knowledge of human immunodeficiency virus serostatus on accuracy of cervical cytologic diagnosis.

BACKGROUND: Women who are infected with the human immunodeficiency virus (HIV) are at high risk of human papillomavirus-persistent infections. Invasive cervical cancer is listed among the illnesses associated with the acquired immunodeficiency syndrome. The objective of the current study was to investigate whether, in South Africa, the accuracy of abnormal cytology confirmed by a histological diagnosis using loop electrosurgical excision procedure (LEEP) is affected by knowledge of the woman's HIV serostatus. METHODS: Of 7648 biopsy specimens, 941 were LEEPs indicated by a cytology report of low-grade squamous intraepithelial lesion or high-grade squamous intraepithelial lesion. A total of 618 specimens (65.7%) were from HIV-uninfected women and 323 specimens (34.3%) were from HIV-infected women. Those women with an unknown pre-LEEP cytological diagnosis were excluded from the study. RESULTS: The total prevalence of HIV infection among the 7648 patients was 18.6%, reflecting its prevalence in the general population of women aged 15 to 49 years. The rate of HIV infection among 3462 women with invasive cervical cancer was 10.7%. The overall prevalence of preinvasive lesions was 73.9% in HIV-infected women compared with 50.3% in women not infected with HIV (P<.0001). The concordance and discordance rates between cytology and histology were similar in uninfected and infected women (P =.93 and P =.18, respectively). Among HIV-infected women, 79.1% of discordant results were due to cytological overdiagnosis; among HIV-negative women, 86.5% of discordant results were due to underdiagnosis (P<.0001). CONCLUSIONS: It appears that the finding of a higher prevalence of preinvasive lesions combined with the knowledge of a patient's HIV-positive serostatus prompts more cytological overdiagnosis, thereby resulting in avoidable LEEP interventions.

Cervical excisional treatment of young women: a population-based study.

OBJECTIVE: Assessment of cytology and biopsy results preceding cervical excisional treatment and their association with excisional histology, to evaluate compliance with treatment recommendations and the potential effect of revisions in cervical histology terminology and usage. METHOD: Data from a unique statewide population-based screening registry was used to describe the use and histologic outcomes of cervical excisional procedures in the year following an abnormal cervical screening cytology. RESULTS: From 2007 to 2011, LEEP rates decreased 87%, 45%, and 16% for women aged 15-20, 21-24, and 25-29 years, respectively. Reductions were attributable to an overall decline in cervical screening and colposcopy, and a decrease in LEEP following a diagnosis of less than cervical intraepithelial neoplasia grade 2 (0.7) for women aged 30-39 years. Irrespective of age, CIN2 was the most common histologic antecedent of excisional treatment (42%), with most (80%) preceded by

Human papillomavirus type-specific persistence and recurrence after treatment for cervical dysplasia.

Human papillomavirus (HPV) infection is a necessary factor in the cervical cancer development. Also after treatment for cervical dysplasia, HPV can be present and promote the recurrence of cervical disease. In the present study, the aim was to perform a long-term follow-up on the ability of HPV testing with genotyping, as compared with cytology, to predict recurrence of high-grade cervical intraepithelial neoplasia and to evaluate the effectiveness of treatment with loop electrosurgical excision procedure (LEEP) conization. Cervical samples for HPV DNA testing and cytological analysis were obtained from 178 women with abnormal smears referred for treatment with LEEP conization. These women were scheduled for HPV DNA testing and Pap smears before and 3, 6, 12, 24, and 36 months after treatment. Three years after treatment 3.1% (N = 4) of women were still persistently HPV-positive with the same type as had been detected at treatment. Recurrent or residual cervical intraepithelial neoplasia II+ in histopathology was found among 9 (5.1%) women during follow-up. All of these women had type-specific HPV-persistence (sensitivity 100% [95% CI 63-100%] and specificity 94.7% [89.8-97.4%]), but only 7/9 had abnormal cytology (sensitivity 77.8% [40.2-96.1%] and specificity 94.7% [89.8-97.4%]). No recurrent or residual disease was found among women with any other patterns of HPV positivity (e.g., type change or fluctuating positivity) (sensitivity 0% [95% CI 0-37.1%] and specificity 80.5% [73.5-86.0%]). In conclusion, only type-specific HPV persistence predicted recurrent or residual disease, and HPV genotyping appears useful to improve the specificity when using HPV testing in post-treatment follow-up.

The accuracy of cervical cancer and cervical intraepithelial neoplasia diagnosis with loop electrosurgical excisional procedure under colposcopic vision.

OBJECTIVE: The colposcopic vision guided loop electrosurgical excisional procedure (LEEP) was studied for the effective diagnosis of cervical cancer and cervical intraepithelial neoplasia (CIN). METHODS: A total of 199 patients participated in this study. Individual cases were from gynecologic outpatients at Thammasat University Hospital, Thailand. These had diagnoses for CIN and were selected for treatment with colposcopic guided LEEP. The average age of patients in this study was 45. Menopausal women represented 31%, (61/199) of the patients. The most frequently found Pap smear result among these women (44%, 88/199), was that of high-grade squamous intraepithelial lesion. The next most frequent Pap smear result (32%, 64/199) was low-grade squamous intraepithelial lesion. Patients' medical records and outcomes were evaluated for consistency of pathological examination between colposcopic directed biopsy and LEEP. Discrepancies between initial diagnosis and the final diagnosis were also analyzed. RESULTS: The colposcopic guided LEEP accurately determined 100% of the cervical cancer cases and 84.8 % of the high-grade squamous intraepithelial lesion cases. Involvement of the ectocervical or endocervical margin regions was found to be 5% and 10% respectively, in this study. Excessive bleeding complication, either during the excision and/or postoperative recovery was found in 3% and 6% of cases, respectively. CONCLUSION: LEEP under colposcopic vision is a recommended technique for ambulatory management of precancerous lesion and early diagnosis of cervical cancer. This technique significantly reduces rate of positive ectocervical cone margin involvement.