Abstract
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.
Cervical cancer remains a significant global health burden, ranking as the fourth most common cancer and a leading cause of cancer-related mortality among individuals worldwide. Preventive strategies, such as effective cervical cancer screening programs and human papillomavirus (HPV) vaccination, have been widely implemented. However, recent stagnation and even slight increase in cervical cancer incidence have been observed, even in countries with well-organized health care systems.1 The disease is primarily attributed to persistent infections with high-risk HPV, which can lead to the development of cervical intraepithelial neoplasia (CIN). The CIN can progress through graded stages (CIN1–3), with surgical treatment (cone biopsy) recommended for most CIN2 or worse (CIN2+) cases.2 Colposcopy with guided biopsies remains a key diagnostic tool for detecting and grading CIN in individuals with positive screening results. However, colposcopy has highly variable sensitivity estimates, with detection rates for CIN2+ lesions ranging from 31%–90%.3,4 A lower sensitivity may result in repeated colposcopy examinations, causing adverse psychological and physical effects,5,6 delayed diagnosis, and an increased risk of missed disease.7
With increasing HPV vaccination coverage and the widespread implementation of HPV-based cervical cancer screening, the landscape of detection cervical disease is shifting.8 Cervical lesions are expected to become smaller and more difficult to visualize during colposcopy, and the overall incidence of CIN is anticipated to decline. This poses challenges in maintaining colposcopist proficiency and accurately distinguishing CIN2+ from insignificant lesions.9 Colposcopy is subjective and prone to intra- and interobserver variability,3 causing diagnostic inconsistencies. Increasing the number of cervical biopsies improves diagnostic accuracy,10 which led the Danish national guidelines to recommend obtaining 4 punch biopsies during colposcopy.11 An alternative approach to improve sensitivity is the use of advanced colposcopy technologies, such as the Dynamic Spectral Imaging System (DSI). The DSI quantifies aceto-white changes on the cervix and generates a color-coded map to guide biopsy site selection. This technology has been shown to improve sensitivity of CIN2+ detection as compared to regular colposcopy.12–20 However, findings across studies are inconsistent and the evidence remains limited, particularly for individuals referred due to positive HPV results and/or low-grade cytology, who represent approximately 75% of colposcopy referrals.21
Therefore, this study aimed to compare the sensitivity of DSI versus regular colposcopy for detecting CIN2+ lesions in individuals referred due to HPV positivity and/or low-grade cytological abnormalities.
METHODS
Setting
In Denmark, individuals aged 23–64 years are invited for cytology or HPV-based cervical cancer screening depending on their age and birth date. Abnormal screening result prompts either retesting or referral for colposcopy, based on the severity of the abnormality.11 In the Central Denmark Region, individuals referred for colposcopy are automatically assigned an appointment at a public gynecology hospital department by a central visitation center. Alternatively, individuals may choose to schedule an appointment at a private gynecology clinic. Cervical cancer screening, follow-up, and treatment, are free of charge at both public hospitals and private gynecological clinics in Denmark. Notably, Denmark implemented a national HPV vaccination program for 12-year-old girls, introducing the quadrivalent vaccine in 2009 and the nine-valent vaccine in 2017.
Study Population and Research Design
This cross-sectional study was conducted between January 2017 and April 2024 at 2 gynecology departments located at Randers Regional Hospital and Horsens Regional Hospital and 1 private gynecology clinic in Aarhus (PGC). Individuals referred for colposcopy with the following criteria were consecutive included: aged ≥18 years and newly referred with a positive HPV test and/or due to low-grade cytology changes, defined as Atypical Squamous Cells of Undetermined Significance (ASC-US) and Low-Grade Squamous Intraepithelial Lesion (LSIL). Exclusion criteria were cervical biopsies taken within the previous 6 months, current or terminated pregnancy within the last 3 months, previous cone biopsy, or prior radiotherapy to the pelvic organs.
Eligible individuals were identified by the colposcopist before the examination, and individuals completed a questionnaire regarding weight, height, smoking habits, contraception use, HPV vaccination status, previous pregnancies, and modes of delivery.
Colposcopy Examination
According to Danish national guidelines, 4 cervical biopsies are taken during colposcopic examination for all individuals, regardless of referral indications, screening history, or colposcopic findings, including cases with or without visible signs of CIN.11
The included individuals were examined with a DSI colposcope (DySIS V3) at Randers Regional Hospital, and with a regular colposcope at Horsens Regional Hospital (Leisegang colposcope) and at the PGC clinic (Olympus colposcope). For all colposcopic examinations, the clinical background of the colposcopist was either trained colposcopy nurses, a resident doctor, or a consultant. In addition, information regarding the colposcopic impression was recorded, including the visibility of the squamous columnar junction (SCJ) and the presence of visible signs of dysplasia.
In the regular colposcopy group, acetic acid (3%) was applied to the cervix prior to the colposcopic examination. The colposcopists were instructed to take the first biopsy from the most abnormal-looking area. Two to three additional biopsies were then taken, either from abnormal-looking area(s) or randomly, ensuring representation from all 4 cervical quadrants. These were not graded in order.
In the DSI group, acetic acid was applied using a built-in applicator system on the DSI colposcope. The DSI technology assesses the intensity of aceto-white changes on the cervix over approximately 120 seconds and generates a color-coded map overlaid on the cervical image, highlighting biopsy-relevant cases. In the DSI group, the colposcopist conducted a regular colposcopy while the DSI system analyzed the cervix. The colposcopist first marked the most abnormal area for the colposcopy-directed biopsy (CDB) prior to viewing the DSI map. The second biopsy was then selected based on the most abnormal area indicated by the DSI map. The colposcopist recorded whether the CDB and DSI-determined locations were the same or different. If the locations matched, 1 biopsy was taken from that site, followed by 3 additional biopsies and if the locations differed, 2 additional biopsies were taken.
Histopathological Evaluation
Each biopsy was placed in separate containers labeled 1–4 for individual histopathological evaluation. Biopsies from Randers and Horsens Regional Hospitals (92.2%) were assessed at the Department of Pathology in Randers, whereas those from PGC (7.8%) were evaluated at the Department of Pathology in Aarhus. Biopsies from Randers and Horsens were examined by 4 gynecological pathologists, with 1 pathologist evaluating 50%–75% of the biopsies. The pathologists were blinded to the biopsy origin (CDB site or the DSI-guided site).
Histopathological evaluation included the CIN grading system and assessment of the presence of the transformation zone (TZ),22 categorizing results as no dysplasia (including inflammation and unspecific reactive changes), CIN1, or CIN2+ (including ungradable CIN, adenocarcinomas in situ (AIS) and squamous cell carcinoma (SCC)). For multiple diagnosis, the most severe histopathological diagnosis was used. Data were obtained from the nationwide Danish Pathology Register.23
Statistical Methods
To test for differences between the 2 independent colposcopy groups, the chi-square test was used for categorical data, while the Mann-Whitney U-test (Wilcoxon rank-sum test) was applied for continuous data. The sensitivity estimates evaluated the ability of individual biopsies to detect CIN2+, using the combined histological diagnosis from all 4 biopsies as the reference standard, which is assumed to provide the most accurate approximation of the true cervical dysplasia severity10. Sensitivities were reported with 95% confidence intervals (CIs) and differences between groups as the primary outcome were compared using a chi-square test. A p-value of ≤ .05 was considered statistically significant. The relative improvements in CIN2+ detection rates between groups were calculated as the percentage increase, determined by dividing the DSI's detection rate by that of the regular colposcopy.
According to unpublished data obtained from Denmark, we expected 35% of individuals referred for colposcopy due to a positive HPV test and/or ASC-US/LSIL cytology would be diagnosed with CIN2+ using regular colposcopy. An improvement of minimum 33% in CIN2+ detection was anticipated with the DSI colposcopy18 compared to regular colposcopy. To achieve a power of 80% with an alpha of 5%, a total of at least 283 individuals was required in each group.
Statistical analyses were performed using STATA 18.0 (Stata Corp LP, College Station, TX) and data were stored in the Research Electronic Data Capture (REDCap) system.24,25
Ethics
All participants provided oral and written informed consent. The study was approved by the national Data Protection Agency (reference number 1–16–02-534-16, dated September 29, 2016). The relevant Committees on Biomedical Research Ethics determined that ethical approval was not required for this project (reference number 1–10–72-262-16, dated November 17, 2016). ChatGPT (OpenAI, San Francisco, CA) was used for language clarity and grammatical accuracy in certain sections of this manuscript.
RESULTS
A total of 905 individuals fitted the inclusion criteria and were enrolled in the study. After study exclusions, 719 (79.4%) individuals were included in the final analysis. Of these, 411 individuals (57.2%) were examined using DSI colposcopy (study group) and 308 (42.8%) individuals underwent regular colposcopy (control group) (Figure 1).
FIGURE 1.
Flow diagram of individuals included in the study.
Baseline characteristics are presented in Table 1. Differences were observed between the 2 groups in terms of referral status, age at inclusion, HPV vaccination status, and parity. In both groups, most individuals were vaccinated against HPV (60.3% vs 72.7%), used contraception (oral or IUD: 59.8% vs 60.4%), and were nonsmokers (56% vs. 66.9%).
TABLE 1.
Baseline Characteristics
| DSI colposcopy n = 411 | Regular colposcopy n = 308 | p | |
|---|---|---|---|
| Referral status | |||
| Referral result, n (%)a | 0.001 | ||
| ASC-US | 91 (22.1) | 49 (16.0) | |
| LSIL | 108 (26.3) | 90 (29.3) | |
| HPV+ with normal cytology | 92 (22.4) | 101 (32.9) | |
| HPV+ with ASC-US or LSIL | 120 (29.2) | 67 (21.8) | |
| Personal information | |||
| Age at inclusion, median (IQR) | 31.4 (24.8–41.2) | 29.3 (24.4–37.0) | 0.006 |
| BMI, median (IQR) | 23.0 (20.9–26.1) | 22.5 (20.7–25.2) | 0.030 |
| Previous positive screening test, n (%)a | |||
| Yes | 155 (37.7) | 121 (39.4) | 0.22 |
| No | 256 (62.3) | 186 (60.6) | |
| Smoking, n (%) | 0.017 | ||
| No | 230 (56.0) | 206 (66.9) | |
| Current | 86 (20.9) | 45 (14.6) | |
| Previous | 94 (22.9) | 55 (17.9) | |
| Unknown | 1 (0.2) | 2 (0.6) | |
| HPV vaccination status, n (%) | 0.003 | ||
| Not vaccinated | 150 (36.5) | 81 (26.3) | |
| Vaccinated | 248 (60.3) | 224 (72.7) | |
| Ongoing | 8 (2.0) | 2 (0.7) | |
| Unknown | 5 (1.2) | 1 (0.3) | |
| Contraception use, n (%) | 0.14 | ||
| Oral | 137 (33.3) | 103 (33.4) | |
| IUD | 109 (26.5) | 83 (27.0) | |
| Condom | 14 (3.4) | 8 (2.6) | |
| Other | 10 (2.5) | 4 (1.3) | |
| None | 138 (33.6) | 101 (32.8) | |
| Unknown | 3 (0.7) | 9 (2.9) | |
| Parity, n (%) | 0.001 | ||
| No previous pregnancies | 182 (44.3) | 178 (57.8) | |
| Previous births | 125 (30.4) | 76 (24.7) | |
| Previous abortions | 21 (5.1) | 16 (5.2) | |
| Both | 82 (20.0) | 34 (11.0) | |
| Unknown | 1 (0.2) | 4 (1.3) |
The percentages (%) represent column percentages, calculated vertically within each column.
aIn the regular colposcopy group, 1 value is missing due to a referral from Italy for suspected moderate cervical cell changes.
Colposcopy-related information is summarized in Table 2. The distribution of the number of colposcopists, their professional background, visibility of SCJ and visible cervical changes differed significantly between the 2 groups. Visible changes were observed in 87.6% of cases in the DSI group and 60.0% in the regular group.
TABLE 2.
Colposcopy Information
| DSI colposcopy n = 411 | Regular colposcopy n = 308 | p | |
|---|---|---|---|
| Different colposcopists, n | 32 | 39 | <0.001 |
| Colposcopy performed, n (%) | <0.001 | ||
| Trained colposcopy nurse | 265 (64.5) | 56 (18.2) | |
| Resident | 115 (28.0) | 90 (29.2) | |
| Consultant | 31 (7.5) | 162 (52.6) | |
| Visible SCJ, n (%) | <0.001 | ||
| Yes, fully | 291 (70.8) | 265 (86.0) | |
| Yes, partially | 120 (29.2) | 43 (14.0) | |
| Visible cervical changes, n (%)a | <0.001 | ||
| Aceto-white | 349 (84.9) | 139 (45.1) | |
| Atypical vessels | 40 (9.7) | 29 (9.4) | |
| Punctuations | 42 (10.2) | 41 (13.3) | |
| Mosaic | 57 (13.9) | 45 (14.6) | |
| No visible changes | 51 (12.4) | 123 (40.0) |
The percentages (%) represent column percentages, calculated vertically within each column.
aIn this the column, the percentages represent a dichotomous variable indicating whether changes were judged to be present (yes) or not (no). A patient may present with more than 1 visible change.
SCJ indicates squamous columnar junction.
Table 3 presents the sensitivity of individual biopsies in detecting CIN2+ and CIN3+ when the final diagnosis was determined by combined results of all 4 biopsies. In the DSI group, a total of 147 individuals (35.8%, 95% CI = 31.1–40.6) were diagnosed with CIN2+ (90 CIN2, 54 CIN3, 2 AIS, 1 SCC) (data not tabulated). In the regular group, 101 individuals (32.8%, 95% CI = 27.6–38.4) were diagnosed with CIN2+ (65 CIN2, 35 CIN3, 1 SCC (data not tabulated). This represents an improvement of 8.4% for DSI. The sensitivity of the CDB for detecting CIN2+ lesions in the first biopsy was 61.9% (95% CI = 53.5–69.7) in the DSI group, compared with 49.5% (95% CI = 39.4–59.6) in the regular group (p < .000). Adding the DSI-directed biopsy to the CDB increased the sensitivity to 69.3% (95% CI = 61.2–76.7%). This sensitivity was based on an average of 1.3 biopsies per individual because the colposcopists and the DSI colormap agreed on the most abnormal area in 64.7% of the cases. Adding the DSI-directed biopsy improved the CIN2+ by 12% compared with the CDB alone in the DSI group (69.3% vs 61.9%) and by 40% compared with the CDB in the regular group (69.3% vs 49.5%).
TABLE 3.
Sensitivity of Biopsies, Along With Their Respective 95% Confidence Intervals (CIs), in Detecting CIN2+ and CIN3+, Were Calculated Using the Combined Results of All 4 Biopsies as the Gold Standard
| Each biopsy, CIN2+ cases | DSI colposcopy, n = 411 | Regular colposcopy, n = 308 | p | Improvement (%) in CIN2+ detection | ||
|---|---|---|---|---|---|---|
| Total cases, n | Sensitivity, n = % (CIs) | Total cases, n | Sensitivity, n = % (CIs) | |||
| Biopsy 1 CDB | 91 | 61.9 (53.5–69.7) | 50 | 49.5 (39.4–59.6) | <0.001 | 25.1 |
| DSI-directed biopsy | 91 | 61.9 (53.5–69.7) | — | — | <0.001a | 25.1a |
| Combination of CDB and DSIb | 102 | 69.3 (61.2–76.7) | — | — | <0.001a | 40.0a |
| Combined biopsies | ||||||
| Biopsy 1 + 2 | 114 | 77.5 (69.9–84.0) | 69 | 68.3 (58.3–77.2) | 0.010 | 13.5 |
| Biopsy 1 + 2 + 3 | 132 | 89.7 (83.7–94.1) | 87 | 86.1 (77.8–92.2) | 0.13 | 4.2 |
| Biopsy 1 + 2 + 3 + 4 | 147 | 100 | 101 | 100 | NA | NA |
| Each biopsy, CIN3+ cases | ||||||
| Biopsy 1 CDB | 34 | 59.6 (45.8–72.4) | 16 | 44.4 (27.9–61.9) | <0.001 | 34.2 |
| DSI-directed biopsy | 33 | 57.9 (45.8–72.4) | — | — | <0.001a | 30.4a |
| Combination of CDB and DSIa | 37 | 64.9 (51.1–77.1) | — | — | <0.001a | 46.2a |
| Combined biopsies | ||||||
| Biopsy 1 + 2 | 42 | 73.7 (60.3–84.5) | 24 | 66.7 (49.0–81.4) | 0.040 | 10.5 |
| Biopsy 1 + 2 + 3 | 50 | 87.7 (76.3–94.9) | 33 | 91.7 (77.5–98.2) | 0.08 | −4.3 |
| Biopsy 1 + 2 + 3 + 4 | 57 | 100 | 36 | 100 | NA | NA |
aBased on a comparison of the sensitivity for Biopsy 1 in the Regular group.
bThis sensitivity was based on an average of 1.3 biopsies per individual.
In both groups, the sensitivity for CIN2+ increased with each additional biopsy. When analyzing 2 biopsies, the sensitivity was 77.5% (95% CI = 69.9–84.0) in the DSI group and 68.3% (95% CI = 58.3–77.2) in the regular group, showing an increase of 13.5%.
For the CIN3+ endpoint, the same tendencies were observed.
The results, stratified by examiner, are shown in Table 4. Trained colposcopy nurses (63.1% vs 41.6%, p = < .001) and consultants (83.3% vs 49.0%, p = < .001) achieved significantly higher CDB sensitivities for CIN2+ in the DSI group compared to the regular group. Combining 2 or 3 biopsies also significantly improved sensitivity for nurses using the DSI colposcope (79.6% vs 58.3%, p = < .001 and 92.2% vs 79.1%, p = .001), respectively.
TABLE 4.
Subanalyses Stratified by Colposcopist: Sensitivity of Biopsies, Along With Their Respective 95% CIs, in Detecting CIN2+ Were Calculated Using the Combined Results of All 4 Biopsies as the Gold Standard
| Each biopsy, CIN2+ cases | DSI colposcopy, n = 411 | Regular colposcopy, n = 308 | p | Improvement (%) In CIN2+ detection |
||
|---|---|---|---|---|---|---|
| Total cases, n | Sensitivity, n = % (CIs) |
Total cases, n | Sensitivity, n = % (CIs) |
|||
| Biopsy 1 | ||||||
| Nurse | 65 | 63.1 (53.0–72.4) | 10 | 41.6 (22.1–63.3) | <0.001 | 51.7 |
| Resident | 21 | 55.2 (38.2–71.3) | 15 | 57.6 (36.9–76.6) | 0.73 | −4.2 |
| Consultant | 5 | 83.3 (35.8–99.5) | 25 | 49.0 (34.7–63.4) | <0.001 | 70 |
| DSI-directed biopsy | ||||||
| Nurse | 64 | 62.1 (52.0–71.5) | — | — | 0.010a | 49.3a |
| Resident | 22 | 57.8 (40.8–73.6) | — | — | 0.98a | −0.4a |
| Consultant | 5 | 83.3 (35.8–99.5) | — | — | <0.001a | a |
| Combination of CDB and DSIb | ||||||
| Nurse | 72 | 69.9 (60.0–78.5) | — | — | <0.001a | 68.0a |
| Resident | 25 | 65.7 (48.6–80.3) | — | — | 0.24a | 14.1a |
| Consultant | 5 | 83.3 (35.8–99.5) | — | — | <0.001a | 41.2a |
| Combined biopsies | ||||||
| Biopsy 1 + 2: | ||||||
| Nurse | 82 | 79.6 (70.5–86.9) | 14 | 58.3 (36.6–77.8) | <0.001 | 36.5 |
| Resident | 27 | 71.0 (54.0–84.5) | 19 | 73.0 (52.2–88.4) | 0.75 | 2.7 |
| Consultant | 5 | 83.3 (35.8–99.5) | 36 | 70.5 (56.1–82.5) | 0.14 | 18.2 |
| Biopsy 1 + 2 + 3: | ||||||
| Nurse | 95 | 92.2 (85.2–96.5) | 19 | 79.1 (57.8–92.8) | 0.001 | 16.6 |
| Resident | 32 | 84.2 (68.7–93.9) | 24 | 92.3 (74.8–99.0) | 0.08 | −8.8 |
| Consultant | 5 | 83.3 (35.8–99.5) | 44 | 86.2 (73.7–94.2) | 0.67 | −3.4 |
| Biopsy 1 + 2 + 3 + 4 | 100 | 100 | NA | NA | ||
| Nurse | 103 | 24 | ||||
| Resident | 38 | 26 | ||||
| Consultant | 6 | 51 | ||||
aBased on a comparison of the sensitivity for Biopsy 1 in the Regular group.
bThis sensitivity was based on an average of 1.3 biopsies per individual.
Conization was performed in 15.7% (n = 113/719) of all eligible individuals (data not tabulated). In the DSI group, 17.0% (n = 70/411) underwent conization, with 88.6% (n = 62/70) diagnosed with CIN2+. In the regular group, 14.0% (n = 43/308) underwent conization, with 93.3% (n = 41/43) diagnosed with CIN2+. The histological diagnosis from the conization specimens was fully concordant with previous cervical biopsy results in the regular group (100% agreement). In the DSI group, histological findings were comparable in 91.2% of cases, whereas 8.8% of cervical biopsies overestimated the severity of lesions. No cases of CIN2+ were missed in cervical biopsies in either group.
DISCUSSION
Our main findings demonstrated that the first CDB biopsy in the DSI group achieved higher sensitivity for detecting CIN2+ compared to the regular colposcopy group. Adding a DSI-directed biopsy further increased sensitivity, resulting in a 12% improvement within the DSI group and a significantly 40% relative increase compared to the regular group. The sensitivity of the DSI-directed biopsy (69.3%) was comparable to that of the first 2 biopsies combined in the regular group (68.3%). With 2 biopsies combined, the DSI group achieved significantly higher sensitivity than the regular group (77.5% vs 68.3.3%, p = .01); however, this difference diminished with additional biopsies, leading to comparable sensitivity between groups when 3 biopsies were performed. Overall, the DSI colposcopy improved the CIN2+ detection rates by 8.4%, substantially below the expected 33%.
These findings contrast with previous studies reporting higher sensitivity for DSI colposcopy among individuals referred with low-grade cytology.12,15,20,26,27 Additionally, the CIN2+ sensitivity in our study was considerably lower than that observed in the ESTAMPA multicentric screening study conducted in LMIC, reporting 90.4% for CIN2+.4 Variations in procedural approaches such as study design and the number of biopsies obtained, however, may limit direct comparisons. Budithi et al.20 observed a significant increase for CIN2+ detection from 27.3% to 86.4% in a prospective study where patients served as their own controls. Louwers et al.26 similarly reported improved detection rates for CIN2+ using DSI (82%) versus regular colposcopy (44%).26 Harris et al.15 reported a 70.9% increase in CIN3+ detection using DSI in a prospective arm compared to a retrospective arm with regular colposcopy. While histological findings from conization specimens are the gold standard, most studies compare colposcopic impressions to biopsy results, which assess individual skills rather than overall procedure performance. This difference may explain the lower increase in CIN2+ detection in our study compared to others.
Our findings indicated that while DSI colposcopy may initially improve sensitivity, this advantage may reflect advancements in optics and imaging quality rather than a true diagnostic benefit of DSI color map. This is supported by the modest increase in sensitivity for the first biopsy when the DSI map was added (61.9% vs 69.3%) and the higher frequency of reported visible aceto-white changes in the DSI group (84.9% vs 45.1%). Similar results were found by Booth et al.,28 though others differed.19
The DSI is designed to assist colposcopists in identifying areas of concern, not as a stand-alone diagnostic method. Therefore, this study evaluated DSI in combination with CDB rather than as an independent diagnostic tool. Sensitivity for CIN2+ detection, stratified by colposcopists' clinical background, showed minor, nonsignificant increases with DSI-directed biopsies for trained nurses and resident doctors. Consultants, however, achieved similar sensitivity regardless of DSI use and performed better than residents and nurses, consistent with previous studies.29 Frequent turnover among residents and colposcopy-trained nurses, as well as limited training, may explain these differences, reflecting a learning curve for colposcopy and underscoring the need for consistent training. However, these findings should be interpreted with caution due to the relatively low number of CIN cases in the stratified analyses.
Adjunctive colposcopy technologies, such as DSI, are proposed to potentially reduce the number of biopsies required, minimizing patient discomfort while maintaining high diagnostic sensitivity. However, our findings show that the sensitivity difference between DSI and regular colposcopy diminishes with additional biopsies. Although DSI colposcopy may be advantageous in settings favoring fewer biopsies, taking at least 4 biopsies per case seems to equalize sensitivity for CIN2+ between methods. Notably, in this study, no cases of CIN2+ were missed in either group when comparing cervical biopsy results to conization histology. These findings highlight the importance of multiple biopsies for improving CIN2+ detection, consistent with previous studies.10,30 In studies with fewer biopsies,4,20,26 for example, where sampling was limited to visible abnormal areas, the true disease status of nonbiopsied tissue remains unknown. This may introduce verification bias and potentially underdiagnosing in both groups. This issue also helps explain the difference in sensitivities observed in our study compared to the ESTAMPA study.4 However, obtaining 4 biopsies may not be feasible in all settings due to economic constraints and pathological workload.
Strengths and Limitations
The well-established cervical cancer screening program and high adherence to the HPV vaccination program in Denmark provide an ideal setting for evaluating adjunctive technologies like the DSI colposcope, which could aid in identifying significant abnormalities in early or minimally developed lesions.
A key strength of this study was its unique possibility to prospectively include patients in a real-world clinical setting over 7 years. This approach ensured a large and diverse patient cohort and involved a broad range of colposcopists (n = 32–39), enhancing the generalizability. In addition, the routine collection of 4 cervical biopsies minimized verification bias and enhanced diagnostic accuracy by providing a close approximation to the true gold standard (conization). However, achieving a true gold standard in this context was not possible because it would require conization for all individuals. Therefore, no false-positive results were reported.
The absence of randomization introduces potential confounding as reflected in patient characteristics (Table 1). The lack of a national accreditation program for colposcopists in Denmark may have contributed to variability in training levels, may also have influenced findings. In addition, the varying set-ups across examination sites during 7 years of inclusion, including differences in the distribution of examinations among colposcopist groups, may complicate attributing the results solely to the diagnostic methods. Furthermore, additional biopsies were not graded in order, making it unclear whether improved detection was due to the DSI map specifically or increased biopsy sampling alone.
CONCLUSIONS
Among individuals referred with positive HPV and/or low-grade cytology, this study revealed that the DSI color-coded map did not provide a clinically significant improvement in CIN2+ sensitivity compared to regular colposcopy. An initial improvement was observed with DSI colposcopy in this study; however, this improvement seems to stem more from the advanced optics and imaging quality of the DSI colposcope rather than from to the DSI color map itself. It highlights the importance of colposcopy quality as a crucial factor in improving the CIN2+ detection rate. Importantly, taking multiple biopsies remained superior for CIN2+ detection in both colposcopy groups.
ACKNOWLEDGMENTS
The authors thank the project inclusion sites and involved pathology departments. In addition, a special thanks to: Tonje Johansen, Department of Pathology, Randers Regional Hospital, Denmark. Henrik Mertz, Department of Pathology, Randers Regional Hospital, Denmark. Eva Hauge, Department of Gynecology and Obstetrics, Randers Regional Hospital, Denmark.
Footnotes
The authors have declared they have no conflicts of interest.
IRB status: All participants provided oral and written informed consent. The study was approved by the Danish Data Protection Agency (reference number 1-16-02-534-16, dated September 29, 2016). The Central Denmark Region's Committees on Biomedical Research Ethics determined that ethical approval was not required for this project (reference number 1-10-72-262-16, dated November 17, 2016) (document in attached file).
Contributor Information
Vibe Munk Bertelsen, Email: vibebert@rm.dk.
Berit Bargum Booth, Email: berit.booth@auh.rm.dk.
Mette Tranberg, Email: mettrani@rm.dk.
Christina Blach Kristensen, Email: chissore@rm.dk.
Mary Holten Bennetsen, Email: maryhans@rm.dk.
Lone Kjeld Petersen, Email: lone.kjeld.petersen@rsyd.dk.
Pinar Bor, Email: isipinbo@rm.dk.
REFERENCES
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