Loop Electrosurgical Excision Procedure Research Articles

Re-Evaluating the Predictive Values of Pap-smear for Diagnosis and LLETZ Margin Status for Management of Precancerous Cervical Lesions

Background: The incidence of HPV infection, precancerous cervical lesions and cervical cancer is relatively high in sub-Saharan African countries. There is significant variability among such countries and worldwide in the accuracy of screening for precancerous cervical lesions and test for cure after excision. Implementation and interval between these procedures also vary. Objective: The aim of this study was to determine the predictive values of Pap-smear for screening and LLETZ for proof-of-cure in a South African hospital setting. Patients and Methods: In the current study, the positive and negative predictive values of Pap-smear screening for the identification of low-grade and high-grade squamous epithelial cervical lesions (LSIL and HSIL, respectively) and Large Loop Excision of the Transformation Zone (LLETZ) procedures for the assessment of residual lesions were determined in a South African hospital setting. Patients referred to the hospital because of abnormal Pap-smear results were included. Results: Pap-smear screening was found to have a positive predictive value of over 90% for HSIL, indicating that this procedure is a reasonable low-cost method of screening for cervical cancer in this setting. Conversely, LLETZ displayed more modest PPV and NPV of 58% and 62%, respectively, for prediction of residual and completely excised lesions. Conclusion: Pap-smear testing had reasonable PPV (>90% for HSIL) to be effectively used as a low-cost screening method in a middle- to low-income South African hospital setting. The predictive values of LLETZ margin status was questionable, justifying careful follow-up after negative margin status. These results justify the consideration of post-LLETZ follow up pap-smear within 3–4 months for both positive and negative margin status, this may prevent under or over treatment of women with precancerous cervical lesions.

Early Mini-Invasive Treatment of Persistent Cervical Dysplasia: Clinical Outcome and Psycho-Relational Impact.

IntroductionAfter the diagnosis of L-SIL, 77. 3% had a persistent infection and anomalous Pap Test results. Many of these patients had highlighted psychological consequences such as anxiety, hypochondria, fear of cancer, and sexual problems. Several studies suggested that the clearance of HR-HPV infection could be accelerated by cervical excisional procedures, especially in L-SIL. In consideration of the psychological implications for HPV infection and related dysplasia in patients with CIN1 at PAP-smear and HR-HPV positivity at least for 6 months, we decided to plan a prospective study where we tried to anticipate excisional cervical using a minimally invasive treatment: thin loop electrosurgical excision procedure (t-LEEP). This study aims to analyze the clearance of HR-HPV after 6 and 12 months, clinical outcomes related to t-LEEP, and the psycho-relational impact at 12 months after t-LEEP.Materials and MethodsWe enrolled patients with the diagnosis of L-SIL at PAP-smear and HR-HPV positivity with a persistent CIN 1 (at least for 6 months), confirmed by cervical biopsy. All enrolled patients underwent t-LEEP. We followed prospectively and performed for all patients the HPV DNA test at 6 (T1) and 12 months (T2) and STAI-Y and FSFI scores at T0 and T2.ResultsWe prospectively enrolled 158 patients, 22 are excluded for the established criteria. Patients with HR-HPV and CIN 1 lesions treated with t-LEEP had an overall clearance of 83.8% at T2. In subgroups analysis at T2, we had a regression: in smoker 71.8%, in contraceptive users 69.5%, in patients aged <25 years 100%, aged 25–30 years 85%, aged 30–35 years 94.4%, aged 35–40 years 92%, and aged ≥40 years 89.1%, in HPV-16 96.4%, in HPV-53 89.5%, in HPV-18 87.5%, in HPV-31 86.6%, and in coinfected 3.5%. STAI-Y and FSFI after t-LEEP (T2) were statistically significant, reducing anxiety status and improving sexual function.ConclusionBased on these results, the use of t-LEEP in patients with persistent CIN 1 and HPV-HR at least for 6 months could be useful for accelerating HPV-HR clearance, in particular, for a subpopulation patient with an increased risk of progression and/or patients with psychological and sexual consequences of carrying an HR-HPV infection.

Adequacy in Endocervical Curettage.

Specimen adequacy is an important quality assurance component of a cervical Papanicolaou test. Although consensus exists on minimal acceptable cellularity for cervical Papanicolaou tests, no such criteria exist for endocervical curettage (ECC) specimens. We sought to identify minimum acceptable cellularity for accurate diagnosis of high-grade dysplasia (HGD) on ECC. All patients with HGD diagnosed in a loop electrosurgical excision procedure (LEEP) from May 8, 2018, to December 18, 2019, and an ECC in the preceding 6 months at our institution were included (n = 51). All ECCs performed before the LEEP were evaluated for cellularity of squamous cells using Aperio eSlide Manager (Leica Biosystems). Biopsy results concurrent with the ECC were noted. We compared the number of squamous cells in positive and negative ECC specimens using a t-test. The proportion of ECC specimens and concurrent biopsies undergoing immunohistochemical (IHC) staining for p16 were compared using the χ2 test. P < .05 was considered significant. Endocervical curettage specimens positive for HGD have increased cellularity compared with negative ECC specimens (mean cellularity, 10,165 vs 1,055; P < .05). Further, IHC staining for p16 was more likely to be performed on an ECC specimen positive for HGD than on a negative ECC specimen (50% vs 3%; P < .05). Biopsies performed concurrently with a negative ECC finding were more likely to undergo p16 IHC than biopsies performed concurrently with a positive ECC finding (51% vs 7%; P < .05). Finally, we observed no difference in the proportion of biopsies undergoing IHC staining for p16 when comparing biopsies positive for HGD with negative biopsies (37% vs 46%; P = .33). We find cellularity of approximately 10,000 cells adequate to diagnose HGD in an ECC specimen and cellularity of approximately 1,000 cells to be inadequate. Further, we find p16 IHC commonly used as a "rule-in" test on ECC specimens at our institution. Biopsies accompanying an ECC specimen negative for HGD are more likely to undergo p16 IHC than those accompanying an ECC specimen positive for HGD, but there is no difference in the proportion of biopsies undergoing p16 IHC when comparing positive and negative results in the biopsies themselves. These findings further support the need for adequate cellularity for diagnosis in ECC, especially when a biopsy is technically difficult. Further areas for exploration include investigating laboratory procedures to maximize the cellularity of ECC specimens.

Loop Electrosurgical Excision Procedure and Cold Knife Conization: which is the best? A large retrospective study

Loop Electrosurgical Excision Procedure and Cold Knife Conization: which is the best? A large retrospective study

Cervical cytology: Radiation and other therapy effects

The different treatment options for carcinoma cervix include radiation, chemotherapy, and surgical treatments. Cytological analysis of smears is crucial for patient follow-up to determine response to therapy and to diagnose the persistence or recurrence of malignancy. Anatomical alterations and changes in cell morphology following radiation or chemotherapy make collecting and interpreting cervical cytology samples difficult. These issues can be mitigated by liquid-based cytology. Ionizing radiation is used in radiotherapy (RT) to kill cells. It is important that cytologists are aware of alterations in morphology of the cells. Radiation can cause cytoplasmic and nuclear changes. Cellular enlargement, vacuolation, granularity loss, and other changes linked with cell death are examples of cytoplasmic alterations. Nuclear enlargement and multinucleation are the most frequent nuclear alterations. These changes are determined by the amount of time that has passed since radiation. It should be emphasized that no one characteristic is pathognomonic. Post-irradiation dysplasia is a condition described as abnormal cellular changes in non-neoplastic epithelial cells after RT. Chemotherapy causes comparable alterations as radiation but impacts fewer cells. Busulfan and other chemotherapeutic treatments may produce morphological alterations, which cytologists must be aware of and able to identify. Immunosuppressive treatments, hormonal therapy, and tamoxifen are some of the other drugs that might cause changes in cervical morphology. Surgical methods used in the detection and treatment of cervical cancer may potentially cause alterations as a result of thermal damage and healing. For the treatment of cervical lesions, electrocautery and the loop electrosurgical excisional procedure are available. These procedures employ electric current ablation leading to ischemic changes in the cervical smear. Cytological analysis of smears following treatment with these modalities necessitates a comprehensive history, kind of therapy, and duration of treatment.

Ultrasound differential diagnosis between amniotic fluid sludge and blood clot from placental edge separation

A 32-year-old G3P1011 patient was followed for a history of loop electrosurgical excision procedure and short cervix in a previous pregnancy. Early transvaginal cervical length at 16 weeks was within normal limits. During a transvaginal ultrasound at 18 weeks of gestation, cervical length was noted to be 3.5 cm. Behind the cervix, amorphous particulate matter was visualized in the amniotic fluid. The matter appeared heterogeneous, wispy, and adjacent to the internal cervical os, but also abutting the edge of the posterior low-lying placenta (Figure, A, yellow arrow; Video).

Epstein-Barr Virus-positive Mucocutanous Ulcer of the Uterine Cervix: Report of a Rare and Evolving Entity.

Epstein-Barr virus (EBV)-positive mucocutaneous ulcer (EBVMCU) is a newly described lymphoproliferative lesion characterized by the proliferation of EBV-positive atypical B cells in a variable inflammatory background associated with mucosal or cutaneous ulcers. Commonly involved sites include the oropharyngeal tract, skin, and gastrointestinal tract, with emerging reports describing EBVMCU of genitalia. To date, no lesions have been described of the uterine cervix. Herein, we report the first cervical EBVMCU incidentally discovered at large loop excision of the transformation zone performed for treating human papillomavirus induced high-grade squamous intraepithelial lesion. The patient was a 35-yr-old, human immunodeficiency virus-positive woman with a history of pulmonary tuberculosis. Histologic and immunohistochemical findings showed classic Hodgkin lymphoma-like features. Systemic lymphoproliferative disease was excluded by appropriate clinical and imaging modalities. This case report highlights the prototypical histologic features of cervical EBVMCU. We emphasize the importance of clinicopathologic correlation to avoid overtreatment of a lesion that can otherwise meet histologic criteria for a lymphoma. Clinicians and pathologists should familiarize themselves with this entity, as this indolent, pseudomaligant lesion typically occurs in immunocompromised patients and spontaneously regresses when the cause for the immunosuppression is addressed.

Literature Review of Cervical Regeneration after Loop Electrosurgical Excision Procedure, and Study Project (CeVaLEP) Proposal.

Objective: To compile existing knowledge on the level of cervical regeneration (detected by ultrasound) after loop electrosurgical excision procedure (LEEP) and to suggest research protocol for further studies. Methods: We conducted a literature search of Medline, Web of Science, Scopus, and Cochrane databases using the keywords “cervix” and “regeneration” without year restrictions. Our eligibility criteria included studies that analysed cervical volume and length regeneration using ultrasound. A literature review was conducted following PRISMA guidelines and registered in PROSPERO (reg. no. CRD42021264062). Information about the studies was extracted from each analysed study on an Excel datasheet and the average regeneration with standard deviation was calculated. All included studies’ possible biases were assessed by the National Institutes of Health’s (NIH) quality assessment tool. Results: The literature search identified 802 papers and four trials (n = 309) that met our criteria. They investigated cervical length and volume regeneration after LEEP using ultrasound, concluding that there is a profound regeneration deficit. Average cervical length regeneration after 6 months was 83.4% (±10.8%) and volume regeneration was 87.4% (±6.1%). All analysed studies had their biases; therefore, based on the conducted studies’ protocols, we present a CeVaLEP research protocol to guide high-quality studies. Conclusion: After LEEP, there is a cervical regeneration deficit. There is a lack of high-quality studies that assess cervical volume regeneration and its relation to obstetrical outcomes. There is a gap in the field and more research is needed to define the prenatal risks related to cervical regeneration.

Loop Electrosurgical Excision Procedure under Propofol Intravenous Anesthesia Combined with Nano-Silver Gel in the Treatment of Cervicitis.

It was aimed at the therapeutic value of loop electrosurgical excision procedure (LEEP) under propofol intravenous anesthesia combined with nano-silver gel in chronic cervicitis. 100 patients with chronic cervicitis were selected and randomly divided into the control group with 50 cases (LEEP under intravenous anesthesia with fentanyl) and the experimental group with the other 50 cases (LEEP under propofol intravenous anesthesia combined with the nano-silver gel). It was suggested from the results that the mean arterial pressure (MAP) and heart rate (HR) (76.88±5.65mmHg, 75.45±5.06beats/min) of patients in the experimental group at T1 time were better than those of the control group (83.76±5.43mmHg, 68.31±5.28beats/min). Visual analogue scale (VAS) (1.85±0.73 points), onset time of anesthesia (0.56±0.21min), time to open eyes (2.45±1.38min) and time of consciousness recovery (5.22±1.42min) were all lower than those of the control group (2.83±0.79 points, 0.93±0.25min, 4.33±1.45min, and 7.15±1.34min, respectively). The incidence of adverse reactions, the effective rate of treatment, the time of wound healing, and the incidence of complications (6%, 94%, 23.83±2.05 days, and 6%, respectively) were all better than those of the control group (24%, 70%, 29.25±2.16 days, and 6%) (P<0.05). All in all, intravenous anesthesia with propofol was beneficial to perform LEEP better, and the combination of LEEP combined with nano-silver gel had an important value in the treatment of chronic cervicitis and was worthy of clinical promotion.

Shear wave elastography: the relationship of the cervical stiffness with gestational age and cervical length- a feasibility study

Objectives To standardize the measurement of shear wave elastography for assessment of cervical stiffness and its relationship with gestational age and cervical length. Methods A prospective cross-sectional study was conducted from September 2017 to March 2019. Data from 125 unselected women (at 11–13 + 6, 18–22 and 24–28 weeks’ gestation) and 55 high-risk women were analyzed for the study. Six regions of interest were evaluated for cervical elastography in the mid-sagittal position by transvaginal ultrasound. Statistical analyses were performed using R statistical language in R-studio. Delivery outcomes were recorded for each patient. Results The shear wave elastography was feasible with good intraoperator and interoperator reproducibility. The endocervical canal and anterior lip internal position had the highest reproducibility (ICC-0.82, 0.75). Shear wave speed was significantly higher in all internal os regions than the external os. There was a statistically significant negative linear relationship of shear wave speed with the gestational age. There was a weak positive relationship between shear wave speed and cervical length. There was no difference between pregnancies with and without spontaneous preterm delivery in shear wave speed measurements and cervical length, although numbers were small for statistical analysis. The internal os of the large loop excision of the transformation zone group was stiffer than the normal population. Conclusion Cervical elastography is feasible and effectively evaluates the tensile properties of the cervix during pregnancy. The most reproducible measurements were obtained at the anterior lip of the internal cervical os. Combining evaluation of cervical elasticity and length might further improve the identification of women at risk of preterm delivery. Currently, technical issues hinder the practical application of shear wave elastography in the clinical setting and require further research and development of the imaging modality.

A Six-Year Gynecological Follow-Up of Immunosuppressed Women with a High-Risk Human Papillomavirus Infection.

Immunocompromised women are at an increased risk of developing malignancies, especially those that are viral-induced, such as invasive cervical cancer caused by the human papillomavirus (HPV). The aim of the study was to describe gynecological follow-up of women undergoing chronic immunosuppressive therapy for various reasons (e.g., kidney/liver transplant, systemic lupus erythematosus), diagnosed with a high-risk HPV (hrHPV) infection based on a self-sampling test. Twenty-six hrHPV-positive women were invited to take part in a gynecological follow-up, including a visual assessment of the anogenital region, two-handed gynecological examination, and cervical cytology as well as a colposcopy and cervical biopsy when necessary. Four women declined taking part in the study. Over six years of observation, low-grade squamous intraepithelial lesions (LSIL) were detected at least once in 7/22 women (31.8%), and a cervical intraepithelial lesion 1 (CIN 1) histopathologic result was obtained five times in 3/22 women. No cases of high-grade squamous intraepithelial lesions, CIN 2/3, or invasive cervical cancers were observed. Loop electrosurgical excision procedure (LEEP) was performed in three patients. As immunocompromised women are prone to persistent hrHPV infections, they should be under strict gynecological supervision because only vigilant surveillance enables fast detection and treatment of early dysplasia and, therefore, provides a chance for the reduction of the cervical cancer burden.

Real-world study of 191 cases with cervical cancer who were diagnosed by loop electrosurgical excision procedure

Real-world study of 191 cases with cervical cancer who were diagnosed by loop electrosurgical excision procedure

294. Abdominal radical trachelectomy as a fertility-sparing treatment for early-stage cervical cancer; a single institution experience

Introduction and aims of the study: The recommended surgical treatment for FIGO stage IA2–IB1 cervical cancer is radical hysterectomy with bilateral pelvic lymphadenectomy. Unfortunately, this procedure leads to loss of fertility. Abdominal Radical Trachelectomy (ART) is a procedure that preserves the uterus without increasing the risk of recurrence while retaining childbearing potential. We describe the surgical, oncologic, and fertility outcomes of patients treated with ART. Methods: We conducted a retrospective analysis of patients undergoing fertility-sparing ART with pelvic lymphadenectomy for early-stage cervical cancer at our institution from 2002 to 2016. Results: A total of 80 patients who underwent ART with pelvic lymphadenectomy were followed for 2–106 months. Thirty-two patients had undergone conization before surgery. The characteristics of the patients included tumor diameter of 8–32 mm (stage IA2 = 10, stage IB1 [b3.2 cm] = 70), average age of 29.5 years (range, 26–43 years), mean operative time of 185 min (range, 142–245 min), and average blood loss of 350 mL (range, 150– 750 mL). Uterine arteries were identified at their origin from the internal iliac artery and gently preserved in 76 cases. There were two recurrences in the paraaortic area treated with chemoradiation (n = 1) and radical hysterectomy (n = 1). Three patients developed high-grade squamous intraepithelial lesions and were successfully treated by loop excision. Forty-five women attempted to conceive, and 34 successful pregnancies were recorded (75%). All of the pregnancies resulted in live births, with a preterm delivery rate of 17.6% (6/34). Conclusions: Our study is one of the largest series of ART to date. Our results show that radical abdominal trachelectomy is feasible and can be performed safely in well-selected patients with cervical cancer who wish to preserve their fertility.

Construction and Evaluation of a Clinical Prediction Scoring System for Positive Cervical Margins Under Colposcopy.

IntroductionCurrently, the commonly used surgical methods for cervical lesions include loop electrosurgical excision procedure (LEEP) and cold knife conization (CKC). However, the positive rate of surgical margins after LEEP is relatively high, which leads to disease recurrence and places further demand on clinical treatment. This study investigated factors related to positive margins after LEEP and established a scoring system to enhance preoperative risk assessment and surgical selection.Materials and MethodsA retrospective analysis of the clinical data of 411 patients undergoing LEEP surgery for cervical lesions in the First Affiliated Hospital of University of Science and Technology of China (USTC), from January 2016 to March 2021, was performed. Cases were divided into a negative margin group (349 cases) and a positive margin group according to postoperative pathology. In the positive group (62 cases), single-factor and multi-factor analyses screened influencing factors; a logistic and additive scoring system was established; furthermore, a ROC curve was used to evaluate scoring effectiveness.ResultsThe positive rate of resection margins after LEEP was 15.1%. Univariate analysis indicated a relationship to patient age, menopause, preoperative ThinPrep Cytology Test (TCT) results, lesion quadrant number under colposcopy, cervical biopsy, and the result of endocervical curettage (ECC). Multivariate analysis showed that age >35 y, menopause, preoperative TCT being high-grade squamous intraepithelial lesion (HSIL), four quadrants being involved under colposcopy, and ECC being HSIL were all independent influencing factors of positive margins after LEEP (P < 0.05). These were included with the above factors to establish a logistic and additive scoring system. When the logistic score was 17, the sensitivity and specificity of predicting positive margins after LEEP were 80.6 and 61.6%, respectively. When the additive score was 6, the sensitivity and specificity were 74.2 and 66.2%, respectively. Both scoring systems had good predictability (area under the curve AUC >0.75).ConclusionsThis study quantified factors influencing positive margins after LEEP and established a scoring system for evaluating patients before surgery to provide a basis for individualized treatment and selection of surgical methods.

Remission of HPV infection after LEEP-conization - a retrospective study.

Human papillomavirus (HPV) infection is one of the most common sexually transmitted diseases. Long-term exposure to the HPV is a known cause of squamous intraepithelial lesions that consequently lead to cervical cancer development. The loop electrosurgical excision procedure (LEEP) conization is an established early cervical cancer treatment method. We aim to assess the remission of HPV infection after LEEP in non-vaccinated patients with pre-cancerous cervical lesions and establish the efficacy of cervical cancer prophylaxis. We analyzed 31 LEEP conizations performed due to low and high-grade squamous intraepithelial lesions in 2019-2020. We obtained molecular test samples and detected DNA of 37 different HPV genotypes. After a six-month follow-up, each patient underwent subsequent high-risk HPV testing and genotyping. We observed that 54.8% of qualified patients were infected with HPV 16. We discovered complete viral remission in 64.5% of cases. After surgery, margins were negative in 71% of the patient's samples. During the follow-up, six patients got infected with new strains of HPV. We found that a correctly performed LEEP conization may contribute to the remission of persistent HPV infection; a more extended follow-up period might be recommended due to a high rate of post-surgery HPV infections.

Experiences and preferences towards collecting a urine and cervicovaginal self-sample among women attending a colposcopy clinic

The effectiveness of cervical cancer screening is hampered by low attendance rates. The collection of a urine sample is hypothesized to engage non-attenders in cervical cancer screening. The aim of this prospective cohort study was to evaluate experiences of women on urine collection and cervicovaginal self-sampling in a home-based setting and preferences for future cervical cancer screening. This study included 140 women, with a median age of 40 years, who were planned for a large loop excision of the transformation zone (LLETZ) procedure. All women collected a urine sample using conventional urine cups and a cervicovaginal self-sample prior to the LLETZ in a home-based setting. Following sample collection, women filled in a questionnaire. Results showed that the instructions of urine collection and cervicovaginal self-sampling were considered clear (95%, 95%CI: 88–98; 92%, 95%CI: 83–96, respectively). Women considered urine collection compared to cervicovaginal self-sampling to be more acceptable (p < 0.001), and to provide more reliable results (p < 0.001). The three highest reported preferred sampling methods for future cervical cancer screening were: urine collection (n = 39, 28%, 95%CI: 19–39), clinician-taken cervical scrape (n = 32, 23%, 95%CI: 15–34), and equal preference for urine collection, clinician-taken cervical scrape and cervicovaginal self-sampling (n = 30, 21%, 95%CI: 14–32). In conclusion, urine collection and cervicovaginal self-sampling are acceptable sampling methods, considered easy to collect in a home-based setting, and moreover, considered trustworthy. Although these results are promising, more research is required to determine if urine collection also lowers the barrier for non-attendees and, thereby, increases the attendance rates of cervical cancer screening.

A uterine cervix supporting device (Con-CapTM) for reducing canal stenosis after Loop Electrosurgical Excisional Procedure.

Cervical stenoses are one of the main long-term consequences after conization of the uterine cervix. The purpose of this study was to evaluate the safety and efficacy of a uterine cervix supporting device (Con-CapTM) in reducing uterine cervical stenosis after Loop Electrosurgical Excisional Procedure (LEEP). We enrolled 112 patients who underwent LEEP between March 2017 to May 2019. Con-CapTM was inserted into the uterine endocervical canal for 4 weeks after LEEP. Laboratory values and clinical symptoms were evaluated. The presence of uterine cervical narrowing was determined at 2 weeks after removal of the Con-CapTM. Data were analyzed using the two-sample t test and χ2 test. A total of 78 women completed the 6-week study period. Thirty-four patients did not complete the study period. The diameter of the uterine cervical canal was significantly greater at postoperative 6 weeks than preoperatively (Hegar dilator No, 2.10 ± 0.56 vs. 3.21 ± 0.71, P< 0.01). The complications were acceptable. Con-CapTM can be used to reduce uterine cervical stenosis safely and effectively after conization of uterine cervix.

Topical imiquimod compared with conization to treat cervical high-grade squamous intraepithelial lesions: Multicenter, randomized controlled trial

ObjectiveIn a previous phase II trial, we showed that topical imiquimod (IMQ) therapy is an efficacious treatment for high-grade squamous intraepithelial lesion (HSIL). Aim of the present study was to investigate the non-inferiority of a 16-week topical, self-applied IMQ therapy compared to large loop excision of the transformation zone (LLETZ) in patients diagnosed with HSIL. MethodsPhase III randomized, controlled, multicenter, open trial performed by Austrian Gynecologic Oncology group. Patients with histologically proven cervical intraepithelial neoplasia (CIN)2 (30 years and older) or CIN3 (18 years and older) and satisfactory colposcopy were randomized to topical IMQ treatment or LLETZ. Successful treatment was defined as negative HPV high-risk test result 6 months after start of the treatment. Secondary endpoints were histological outcome and HPV clearance rates. ResultsWithin 3 years 93 patients were randomized, received the allocated treatment and were available for ITT analysis. In the IMQ group negative HPV test at 6 months after treatment start was observed in 22/51 (43.1%) of patients compared to 27/42 (64.3%) in the LLETZ group on ITT analysis (rate difference 21.2%-points, 95% two-sided CI: 0.8 to 39.1). In the IMQ group histologic regression 6 months after treatment was observed in 32/51 (63%) of patients and complete histologic remission was observed in 19/51 (37%) of patients. Complete surgical resection was observed in 84% after LLETZ. ConclusionIn women with HSIL, IMQ treatment results in lower HPV clearance rates when compared to LLETZ. LLETZ remains the standard for women with HSIL when treatment is required.Clinical Trial Registration: ClinicalTrials.gov Identifier: NCT01283763, EudraCT number: 2012-004518-32.

Posttreatment monitoring by ASCL1/LHX8 methylation analysis in women with HIV treated for cervical intraepithelial neoplasia grade 2/3

Women with HIV (WWH) have an increased risk to develop recurrent cervical intraepithelial neoplasia grade 2/3 (rCIN2/3) after treatment compared with HIV-negative women. Therefore, appropriate posttreatment monitoring of WWH is important. This study evaluates the performance of ASCL1 and LHX8 methylation analysis as posttreatment monitoring test in WWH treated for CIN2/3, as alternative to cytology or human papillomavirus (HPV) as follow-up test. Prospective observational cohort study. WWH treated for CIN2/3 by large loop excision of the transformation zone (LLETZ) (n = 61) were invited for follow-up study visits at 1, 2.5 and 4 years after baseline. Baseline and follow-up cervical scrapes were tested for cytology, HPV and DNA methylation of ASCL1 and LHX8 genes. The performance of these strategies for the detection of rCIN2/3 was evaluated in the first follow-up cervical scrape. Thirteen (21.3%) rCIN2/3 lesions were detected within 4 years of follow-up. In women without rCIN2/3 in follow-up, methylation levels of ASCL1 and LHX8 decreased significantly after LLETZ treatment (P = 0.02 and 0.007, respectively). In women with rCIN2/3, methylation levels remained high after LLETZ treatment. The 4-year rCIN2/3 risk was 4.9% (95% CI: 0.6-16.5) for ASCL1/LHX8-negative women, 8.1% (95% CI: 1.7-21.9) for HPV-negative women and 7.7% (95% CI: 2.1-18.5) for cytology-negative women. A negative ASCL1/LHX8 methylation test in follow-up is associated with a low rCIN2/3 risk and could serve as an objective test of cure and well tolerated alternative for HPV and/or cytology screening in the posttreatment monitoring of WWH.

Role of Dual-Staining p16/Ki-67 in the Management of Patients under 30 Years with ASC-US/L-SIL.

Patients diagnosed with low-grade squamous intraepithelial lesion ((L-SIL) or atypical squamous cells of undetermined significance (ASC-US) are subjected to additional investigations, such as colposcopy and biopsy, to rule out cervical intraepithelial neoplasia 2+ (CIN 2+). Especially in young patients, lesions tend to regress spontaneously, and many human papilloma virus (HPV) infections are transient. Dual-staining p16/Ki-67 has been proposed for the triage of patients with ASC-US or L-SIL, but no prospective study addressing only this subgroup of patients has been conducted so far. We performed a prospective study including all eligible patients referred for a loop electrosurgical excision procedure (LEEP) in the Department of Obstetrics and Gynecology of Timișoara University City Hospital. HPV genotyping and dual-staining for p16/Ki-67 were performed prior to LEEP, at 6 and 12 months after LEEP. A total of 60 patients were included in the study and completed the follow-up evaluation. We analyzed the sensitivity and specificity for biopsy-confirmed CIN2+ using the 95% confidence interval (CI) of high-risk human papilloma virus (HR-HPV), dual-staining p16/Ki-67, colposcopy, and combinations of the tests on all patients and separately for the ASC-US and L-SIL groups. Dual-staining p16/Ki-67 alone or in combination with HR-HPV and/or colposcopy showed a higher specificity that HR-HPV and/or colposcopy for the diagnosis of biopsy confirmed CIN2+ in patients under 30 years. Colposcopy + p16/Ki-67 and HR-HPV + colposcopy + p16/Ki-67 showed the highest specificity in our study.