Three-Dimensional Transperineal Ultrasound Assessment of the Anal Sphincter Immediately After Vaginal Birth: An Exploratory Study.

OBJECTIVES: To assess the feasibility of acquiring adequate transperineal ultrasound (TPUS) volumes of the anal sphincter (AS) immediately after vaginal birth, the reproducibility of its measurements, and detecting defects therein. METHODS: Secondary analysis of TPUS volumes of the AS, acquired immediately after vaginal birth with a transversely oriented convex probe. Two independent experts ranked off-line image quality as "inadequate," "adequate," or "ideal" using the Point-of-Care Ultrasound Image Quality scale. On "adequate" and "ideal" quality volumes, the length of the external AS at 6 and 12 o'clock, and the volume of the external and internal AS were measured. Additionally, volumes were screened for AS defects on tomographic ultrasound imaging. Subsequently, we rated the intra- and interrater agreement on those findings. RESULTS: Of 183 volumes, 162 were considered "adequate" or of "ideal" quality (88.5%). Reasons for "inadequacy" were shadow artifacts (16/21), poor resolution (3/21), incomplete acquisition (1/21), or aberrant AS morphology (1/21). The intrarater reliability of two-dimensional (2D) and three-dimensional (3D) measurements was excellent, whereas interrater reliability was fair to good for 2D measurements and good for 3D measurements. In those tomographic ultrasound imaging (TUI) sequences including AS defects, the intra- and interrater reliability of the defect measurement were excellent [intraclass correlation coefficient (ICC) = 0.92 (0.80-0.94)] and moderate [ICC = 0.72 (0.63-0.79)]. In this cohort, there were only few (4/48; 8.3%) AS defects. However, grading them was poorly reproducible between experts. CONCLUSION: TPUS of the AS immediately after vaginal birth yields adequate image quality and allows for reproducible measurements. In the few patients with AS defects, there was good agreement on the presence, but it was poor for the extent of defects.

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

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

p16/Ki-67 dual stain, PAP cytology and HR-HPV test results prior to and 6 months after a LLETZ procedure: a prospective observational cohort study.

OBJECTIVES: To investigate the effect of a LLETZ procedure on p16/Ki-67 dual stain, PAP cytology and HR-HPV test results on cervical cytology samples obtained prior to and 6 months after the procedure. Secondary aims are to assess dependency between test results at the time of follow-up and explore dual stain positivity rates according to known risk factors for persistence/recurrence of cervical intra-epithelial neoplasia (CIN). STUDY DESIGN: Prospective observational cohort study conducted in the Department of Gynaecology at the University Hospitals of Leuven, Belgium. All patients referred for a LLETZ procedure were invited to participate. A cervical cytology sample was obtained just prior to and 6 months after the procedure. Every sample was used for PAP staining (cytology), p16/Ki-67 dual staining (dual stain test, DST) and HR-HPV genotyping. Test results were compared between both timepoints using the McNemar test. Dependency was assessed cross-sectionally at the time of follow-up using a chi-squared test. RESULTS: From the 110 participants originally included, 83 attended follow-up (75.5%). Mean duration of follow-up was 187.91 days (SD 21.47) and mean age was 41.4 years (SD 11.08). DST positivity rates were 70.9 and 30.1% prior to and 6 months after the procedure (p < 0.001). HR-HPV testing (positive or negative) and abnormal PAP cytology (evaluated at an ASCUS or worse threshold) showed a similar significant reduction in positivity rates (84.5 vs 42.2% and 72.7 vs 28.9%, respectively, p < 0.001). Results of all three assays showed high dependency at the time of follow-up (DST and PAP, PAP and HR-HPV test, DST and HR-HPV test-p values < 0.001). The highest proportion of positive DST results was seen in patients carrying HPV16 (84.6%), followed by any HR-HPV type (60%), those treated for CIN2 + (27.3%) and those with positive margins on the cone specimen (26.7%). CONCLUSION: A LLETZ procedure results in a significant decrease in abnormal DST, PAP cytology and HR-HPV test results in this diverse cohort of patients. The highest proportion of abnormal DST results was seen in patients carrying HR-HPV at the time of follow-up, especially HPV 16.

The use of p16/Ki-67 dual staining technology on cervical cytology of patients undergoing a LLETZ procedure.

OBJECTIVES: The main objective of this prospective observational study was to investigate the diagnostic performance of the p16/Ki-67 dual stain technique (DST) for detecting CIN 2+ in a LLETZ referral setting. Test performances were compared with HR-HPV testing and Pap cytology. METHODS: All patients referred for a LLETZ procedure were candidates for participation in this trial. A total of 110 patients were enrolled between October 2016 and March 2017. From each participant, a cervical cytology sample was obtained before the onset of the LLETZ procedure. On each sample, the dual stain technique (Roche CINtec PLUS ® test), Pap cytology and an HPV DNA assay (identifying 17 different HPV types) were performed. RESULTS: The overall disease prevalence of CIN 2+ was 56%. The mean age was 41 years, with 38% of patients being younger than 35 years. The overall sensitivity and specificity of the dual stain technique for detecting CIN 2+ was 94% (95% CI: 84.30-98.21%) and 58% (95% CI: 43.21-72.93%) respectively with a PPV of 74% (95% CI: 67.34-80.31%) and a NPV of 88% (95% CI: 72.48-94.90%). HR-HPV testing results in a similar sensitivity of 92% (95% CI: 82.17-97.33%) but considerable lower specificity of 21% (95% CI: 11.17-33.35%) compared to the dual stain technique. At an ASCUS or worse threshold, Pap cytology had the lowest sensitivity of 89% (95% CI 78.11-95.34%) compared to dual staining and HR-HPV testing. Specificity was better (48% with 95% CI of 33.29-62.81%) than that of HR-HPV testing but not as good as the DST. CONCLUSION: p16/Ki-67 dual staining provides high sensitivity and improved specificity compared to HR-HPV testing and Pap cytology for detecting CIN 2+, making it an interesting tool for identifying relevant disease in patients referred for a LLETZ procedure.