Vibe Munk Bertelsen

Dynamic Spectral Imaging and Regular Colposcopy in CIN2+ Detection for HPV-Positive and/or Low-Grade Cytology Referrals

Objectives Dynamic Spectral Imaging colposcopy (DSI), an AI-driven technology, may improve cervical cancer diagnostics. This study aimed to evaluate the cervical intraepithelial neoplasia grade 2 or worse (CIN2+) sensitivity of DSI compared to regular colposcopy in individuals referred due to human papillomavirus (HPV)-positive and/or low-grade cytology. Methods This multicenter comparative cross-sectional study included individuals aged ≥18 years referred for colposcopy due to HPV positivity and/or low-grade cytology. Participants underwent either DSI or regular colposcopy. Colposcopists first identified the most suspicious area; in the DSI group, this was done before reviewing the DSI color map. The worst colored area was then selected, followed by additional biopsies. All participants had 4 cervical biopsies taken, with the most severe diagnosis as the gold standard. The primary outcome was CIN2+ detection sensitivity comparison between groups using a chi-square test. Results A total of 411 individuals underwent examination with DSI and 308 had regular colposcopy. The sensitivity for detecting CIN2+ with DSI was 69.3% (95% CI = 61.2–76.7) with an average of 1.3 biopsies, comparable to the sensitivity of the regular group when 2 biopsies were taken (68.3%, 95% CI = 58.3–77.2). No significant sensitivity differences were observed between groups when 3 or 4 biopsies were combined. Conclusion The DSI color map did not show a clinically significant improvement in CIN2+ detection sensitivity compared to regular colposcopy. However, multiple biopsies enhanced sensitivity and remained superior for CIN2+ detection in both colposcopy groups.

Improving diagnostic of cervical dysplasia among postmenopausal women aged ≥50 years using local vaginal oestrogen treatment prior to colposcopy: study protocol for a multicentre randomised controlled trial (the IDEAL study)

Introduction Colposcopy is the most important diagnostic tool to detect cervical precancerous lesions and thereby prevention of cervical cancer. Due to age-dependent changes of the cervix, colposcopy is challenging in postmenopausal women, as the majority will have a non-visible transformation zone, resulting in increased risk of missing disease, a diagnostic cone biopsy and prolonged follow-up with repeated colposcopies. This study will be among the first to investigate, if treatment with vaginal oestrogen prior to colposcopy will improve the colposcopy performance, to ensure accurate and timely diagnosis of precancerous cervical lesions among postmenopausal women. Methods and analysis A randomised blinded controlled multicentre study. Enrolment will be performed at gynaecology departments in Central Denmark Region and Region of Southern Denmark. A total of 150 postmenopausal women aged ≥50 years referred for colposcopy due to abnormal cervical screening results will be randomised 1:1 to either pretreatment with vaginal application of Vagifem 30 µg or placebo once a day for 14 days prior to colposcopy. The primary outcome will be to compare the percentage of women in the two groups with a visible transformation zone at colposcopy, and biopsies representative of the transformation zone. Secondary outcomes will be the proportion of detected cervical intraepithelial neoplasia grade 2 or higher in the cervical biopsies; the proportion of diagnostics cone biopsies; the patients’ report on possible side effects and compliance to the pretreatment. Ethics and dissemination The study has been approved by the Central Denmark Region Committee on Biomedical Research Ethics (1-10-72-34-22), the Central Denmark Regions’ Research Unit (1-16-02-72-22) and The Danish Health Authority (Danish Medicine Agency; 2022015030). The study’s EudraCT number is (1-23-456; 2022-000269-42) and it is registered on www.clinicaltrials.gov . The local Good Clinical Practice (GCP) unit will supervise and monitor the study closely before, during and after the study period. Findings will be disseminated in peer-reviewed scientific journals and presented in relevant conferences. Trial registration number NCT05283421 .

Improving Diagnostics in Cervical Dysplasia

Cervical cancer is the fourth most common cancer in women worldwide. It is caused by an infection with human papillomavirus (HPV). A persistent infection with HPV is associated with increased risk of precancerous lesions, which may further develop into cervical cancer. To reduce the disease burden, accurate and timely diagnosis of cervical precancerous lesions are crucial. To identify cervical precancerous lesions, women are referred to colposcopy, which is the most important diagnostic tools to detect cervical precancerous lesions. It allows close visualization of the cervix in order to collect biopsies in the area called transformation zone (TZ), which is where precancerous lesions develop. It is essential for the physician to identify the TZ during colposcopy in order to obtain correct diagnosis. For women aged ≥50 this is often a challenge as TZ naturally with age, will retract further into the cervical canal, making the area for sampling invisible, and thereby the colposcopy inadequate. Consequently, this increases the risk of developing cancer due to diagnostic delay, and the risk of several colposcopy examinations or overtreatment (cone biopsy), before a final diagnosis is achieved. Few studies suggest that pretreatment with local vaginal estrogen prior to colposcopy may improve visualization of the TZ. Thereby, obtaining more accurate biopsies from the cervix, and thus making a more accurate and timely diagnosis in the first outpatient visit. The primary purpose of this study is to evaluate pre-diagnostic treatment with estrogen to improve the diagnosis of women with cervical precancerous lesions, in order to prevent cervical cancer. The study ia s randomized controlled double-blind multicenter study. The investigators will use information from Danish National Patient registry, and data from the Danish Pathology Data Bank. Enrollment will take place at the Departments of Gynecology in Denmark. Eligible women aged ≥ 50 years will be randomized 1:1 to receive local vaginal estrogen or placebo prior to the colposcopic examination. The investigators believe the results will provide the prerequisite for obtaining correct diagnosis, and thereby provide basis for choosing the right individualized examination- and treatment plan. The results will also contribute with important knowledge, that may help reduce the incidence and mortality rate of cervical cancer.