Sequential Application of Lugol’s Iodine Test after Acetic Acid for Detecting Cervical Dysplasia: A Prospective Cohort Study

Abstract

Applying Lugol’s iodine solution to the cervix followed by colposcopic assessment is an established standard test to identify low grade/high grade squamous intraepithelial lesions (LSIL/HSIL). Here, we assessed the performance of Lugol’s iodine test during colposcopy using a standardized protocol with 5% acetic acid followed by 5% Lugol’s iodine solution and recording the most severe acetowhite (MSAWL) and iodine-negative (MSINL) lesions in a prospective cohort of consecutive women referred to our specialized colposcopy unit. The primary study endpoint was the sensitivity/specificity of MSINL for the detection of LSIL/HSIL. Secondary endpoints were the time to first appearance of the MSINL, MSINL staining intensity, and fading of MSINL. Three hundred and twenty women were included. The sensitivity and specificity of MSINL for the detection of LSIL/HSIL was 81.4 (95%—confidence interval (CI) 77.3–85.0)% and 29.5 (24.2–35.5)%, respectively. Ninety-six MSINL were identified exclusively by Lugol’s iodine test (no pathology, n = 46; LSIL, n = 29; HSIL, n = 21) (number needed to biopsy to identify one additional LSIL/HSIL = 1.9). In 17/320 (5.3%) patients, the clinical management was changed based on the result of Lugol’s iodine test. Video analysis showed an instant appearance of the MSINL within 10 s in 100% of cases. Intensity of MSINL significantly correlated with the presence/absence of LSIL/HSIL (Spearman rank order correlation; p < 0.0001). Fading of iodine-induced staining intensity over time was not observed. Thus, Lugol’s iodine showed moderate sensitivity and poor specificity, but changed clinical management in 5% of cases when used in addition to acetic acid.

Innovative Diagnostic and Therapeutic Interventions in Cervical Dysplasia: A Systematic Review of Controlled Trials

“…Using the remaining 37 citations, cross reference searching identified two further appropriate citations. Thus, in summary, 39 citations reporting on diagnostic and therapeutic interventions in women with cervical dysplasia within a controlled trial setting were included in this review [ 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 ]. Among them, we found 5 PCTs [ 13 , 14 , 15 , 16 , 17 ] and 28 RCTs [ 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , …”

“…We identified 12 studies. In total, 8 studies with 1390 participants were RCTs [ 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 ] and 4 studies with 893 participants were PCTs [ 13 , 14 , 15 , 16 ]. In 7 RCTs, interventions aimed at reducing pain during colposcopy and colposcopically-controlled cervical biopsies were evaluated [ 18 , 20 , 21 , 22 , 23 , 24 , 25 ].…”

“…One RCT looked at bleeding control after colposcopically-controlled biopsies by use of Monsel’s solution demonstrating that Monsel’s solution was efficacious in reducing blood loss and duration after biopsies [ 19 ]. Two PCTs evaluated the optimal use of the acetowhite acid test [ 14 ] and Lugol’s iodine test [ 16 ]. The best time to identify acetowhite lesions was 1 min after the application of acetic acid with fading of acetowhite lesions being common and time-dependent supporting a recommendation of not prolonging colposcopy beyond 3 min [ 14 ].…”

“…The best time to identify acetowhite lesions was 1 min after the application of acetic acid with fading of acetowhite lesions being common and time-dependent supporting a recommendation of not prolonging colposcopy beyond 3 min [ 14 ]. Lugol’s iodine showed moderate sensitivity and poor specificity, but it changed the clinical management in 5% of cases when used in addition to acetic acid [ 16 ]. Finally, one PCT found that 4 random cervical biopsies at the squamocolumnar junction resulted in an optimal yield of cervical intraepithelial neoplasia (CIN) 2+ lesions in women with a cytology of LSIL or Atypical Squamous Cells of Undetermined Significance (ASCUS) who had a normal colposcopic impression [ 15 ].…”

“…Therefore, evidence-based diagnostic and therapeutic interventions for LSIL/HSIL are an important worldwide medical need. In order to clarify what progress has been made in this field during the last decade, we systematically searched the literature between 2012 and 2021 and identified 39 high-quality controlled trials, RCTs, and PCTs, reporting on diagnostic and therapeutic interventions in women with cervical dysplasia [ 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 ]. Among them, we found 5 PCTs [ 13 , 14 , 15 , 16 , 17 ] and 28 RCTs [ 18 , 19 , 20 , 21 , 22 , 23 , 24 , ...…”