Clinical trial NCT05870787: IMproving the DIagnostics and Treatment of CeRvical Precancer
Official title: IMproving the DIagnostics and Treatment of CeRvical Precancer
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Cervical Dysplasia
Cervical Disease
Cervical Lesion
Cervical Cancer
Cervical Neoplasm
Lead sponsor: University of Aarhus
Sponsor class: OTHER
First posted: 2023-05-23
Enrollment: 1299
Sex: FEMALE
Minimum age (years): 23
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Women with abnormal smear (HPV-genotype and cytology) referred to colposcopy, visibel transformation zone (type 1 or 2) and where cervical biopsies has been sent to pathology examination.

Brief summary: Cervical cancer screening is important as it enables identification of women at increased risk of the disease, but high-quality diagnostics of screen-positive women and effective treatment of those with precancer are critical in preventing progression to cancer. With the current transition from cytology-based to primary human papillomavirus (HPV)-screening and a growing proportion of HPV-vaccinated women, diagnostics of screen-positive women will become more challenging in the decades to come. Thus, there is a need to explore how to improve diagnostics while ensuring a low number of unnecessary procedures such as colposcopy and the collection of multiple cervical biopsies.

The overall purposes are:

Purpose 1: To investigate the diagnostic accuracy of cervical precancer when using a colposcopic scoring system in the diagnostic work-up of screen-positive women.

Purpose 2: To investigate the performance of a colposcopic scoring system to identify women without cervical precancer in whom collection of biopsies can be safely omitted.

Detailed description: Introduction Cervical cancer is the fourth most common cancer in women worldwide. Every year, 375 women are diagnosed with cervical cancer in Denmark, and approximately 90 women die from the disease. Cervical cancer is caused by the sexually transmitted virus, human papillomavirus (HPV). When infected about 85-90 % clear the virus within a year or two. The remaining women develop a persistent HPV infection, which is associated with an increased risk of cervical intraepithelial neoplasia (CIN), which may progress to cancer if left untreated. Cervical cancer can be prevented through prophylactic HPV vaccination and screening. In Denmark, women aged 23 - 64 years are invited to the screening program. Women who do not participate in regular screening have an increased risk of cervical cancer, however up to 55% of cervical cancers are diagnosed in women who have attended screening. Hence, the performance of diagnostics is crucial.

Diagnostics Women with abnormal screening results may undergo repeat testing or be referred for colposcopy. Colposcopy allows the colposcopist to magnify and visualize the cervix with the transformation zone, where cervical cancer and cervical lesions typically arise. The aim is to make a colposcopic diagnosis and select the most severe area for biopsies, which undergo histopathological examination. Studies have shown considerable inter- and intra-observer variability even among experienced colposcopists, and a variable sensitivity of colposcopy as low as 55-57%. These findings suggest a need to improve the detection rate of CIN2+. A validated colposcopic scoring system, the Swede score, has been designed to improve the detection of high-grade cervical lesions, specified as cervical intraepithelial neoplasia grade 2 or worse (CIN2+) by providing an systematic approach to the colposcopy examination. The Swede score includes five variables (degree of 1) acetowhitening, 2) margins and surface, 3) vessels, 4) lesion size, and 5) iodine staining by using Lugols iodine) with a score from 0 - 2. Conventional colposcopy only utilizes acetic acid. In the original study, the Swede score had a high sensitivity and specificity for detecting high-grade cervical lesions (CIN2+), with an area under the receiver operating characteristics (ROC) curve of 0.87. Even so, the Swede score is endorsed by the International Agency for Research on Cancer (IARC/WHO) and by the European Federation for Colposcopy (EFC), it has not yet been implemented in Denmark. As previous studies have mostly evaluated the use of the Swede score among expert colposcopists, it is important to assess whether the score may be a valuable tool among non-experts. In Denmark, colposcopy is mostly performed by non-experts gynecologists. As a result of the low performance of colposcopy, and because several studies have shown that the CIN2+ detection rate increases with the number of biopsies collected, the Danish national guidelines recommend that all women should have a minimum of 4 biopsies collected. Biopsies should be collected from abnormal areas of the cervix and, if no lesion is detected, random biopsies should be taken. Our neighboring Scandinavian countries, for example Sweden and Finland, do not recommend collection of random biopsies. If biopsies could be omitted without increasing the risk of missing disease and reducing the harms with pain, bleeding and discomfort, this would benefit the women.

Aim

The project aims to explore whether the implementation of a systematic colposcopic scoring system, the Swede score, can:

Pupose 1: Improve diagnostic accuracy of cervical lesions with detection of CIN2+ in a Danish clinical setting.

Purpose 2: Evaluate whether the Swede score can be used to assess cervical lesions with \<CIN1, so random biopsies can be safely omitted.

Data Characteristics of the women will be collected from medical records (previous gynecological historic, parity, smoking status, HPV-vaccination status, hormone use or immunosuppressive treatment). From the Danish Pathology Databank, we will collect data on previous screening history, result of the referral screening test, result of current and subsequent cervical biopsies and/or cervical excision.

Eligibility criteria: Inclusion Criteria:

* Women referred to colposcopy due to abnormal smear (HPV-genotype and cytology) in Central Denmark Region or Southern Denmark Region.

Exclusion Criteria:

* Allergic to iodine.
* Tranformationzone not visible (type 3).
* Atrophy of cervical epithelium.
* Women referred to colposcopy with no cervical biopsies taken or invalid cervical biopsies.
* Women with previous cone biopsy, hysterectomy or without a cervix due to cervical cancer will be excluded.
* Pregnant women.

Primary outcomes:
measure: Purpose 1: Diagnosis of collected targeted cervical biopsies
timeFrame: When the histological report is available - typically within 12 weeks after the biopsy was taken
measure: Purpose 2: Diagnosis of collected random cervical biopsies
timeFrame: When the histological report is available - typically within 12 weeks after the biopsy was taken
Secondary outcomes:
Other outcomes:
Locations:
city: Fredericia
country: Denmark
facility: Guldberg Kvindeklinik
city: Herning
country: Denmark
facility: Gødstrup Regional Hospital
city: Horsens
country: Denmark
facility: Horsens Gynækologisk Klinik
city: Horsens
country: Denmark
facility: Horsens Regional Hospital
city: Odense
country: Denmark
facility: Odense Univeristy Hospital
city: Randers
country: Denmark
facility: Randers Regional Hospital
city: Viborg
country: Denmark
facility: Viborg Regional Hospital
Study officials:
affiliation: University of Aarhus
name: Anne Hammer, MD, as.prof
role: STUDY_CHAIR
affiliation: Aalborg University Hospital
name: Ulrik Schiøler Kesmodel, MD, prof
role: STUDY_CHAIR
affiliation: Randers Regional Hospital
name: Berit Bargum Booth, MD, Ph.d.
role: STUDY_CHAIR
affiliation: Aarhus University Hospital
name: Line Winther Gustafson, MD, Ph.d.
role: STUDY_CHAIR
References: