Original Articles – Cervix and HPV
Almost all high-grade neoplastic lesions of the uterine cervix are located within the cervical transformation zone (TZ). Invasive cervical cancer and cervical intraepithelial neoplasia grade 3 (CIN 3) develop from persistent infections with specific high-risk human papillomavirus types. Herfs et al. proposed that a discrete population of squamocolumnar junction (SCJ) cells with a unique morphology and gene expression profile is more sensitive to human papillomavirus–induced oncogenic transformation than well-differentiated squamous or columnar epithelial cells of the uterine cervix.1 On the basis of this concept, precise identification of the SCJ and evaluation of the complete TZ are the most crucial steps in colposcopy. The International Federation for Cervical Pathology and Colposcopy (IFCPC) underlined this view by introducing a classification comprising 3 different types of TZs (see Figure 1).2 This concept was intended to complement the obligatory description of the SCJ as visible or not visible. A type 1 TZ is located entirely on the ectocervix, a type 2 TZ involves the endocervical canal but the SCJ is still visible, while a type 3 TZ shows endocervical involvement without a fully visible SCJ. Colposcopy is considered inadequate in type 3 TZ, whereas adequate colposcopical evaluation is feasible in types 1 and 2 TZ. The latest update on IFCPC colposcopy terminology confirmed classification of the TZ as an obligatory variable, in addition to providing a description of the visibility of the SCJ and stating whether colposcopy is adequate or inadequate, with the reason given.3
Although convincing, the new classification system has not been investigated systematically for clinical utility in daily practice. Therefore, we do not know whether the classification is used uniformly by all colposcopists or is based on subjective criteria with poorly reproducible results.
Here we report the results from a prospective electronic quality assessment by the German Colposcopy Network (G-CONE) that compared the age-dependent distribution of types of TZ between different colposcopy clinics. We hypothesized that the frequency distribution of 3 types of TZ will be similar in different colposcopy clinics if the IFCPC classification system is highly reproducible.
MATERIALS AND METHODS
From February 2012 to February 2013, 8 colposcopy clinics affiliated to G-CONE prospectively collected data from patients referred for colposcopy, mainly because of abnormal screening results and, to a lesser extent, with diseases of the lower genital tract. Data were collected using ODSdysplasie Version 4.0 (asthenis GmbH; available at http://www.asthenis.de), a software specifically developed to document diseases of the lower female genital tract. ODSdysplasie is currently the only colposcopy benchmarking tool certified by the German Society of Cervical Pathology and Colposcopy and provides continuous independent electronic quality assessment of participating colposcopy clinics. ODSdysplasie was developed in close coordination with G-CONE, resulting in comprehensive software specifically designed to organize and document all aspects of diagnosis, treatment, and follow-up, including digital colposcopy images and histologic, cytologic, and virologic data.
All data collected from women referred for colposcopy were anonymously encrypted and stored in a secure relational database located within the clinics’ network. Access to data for all aspects of benchmarking or certification was restricted to registered users.
Women with a history of hysterectomy were excluded from this analysis. Participating colposcopy clinics were not obliged to document all cases seen during the study period; therefore, the numbers of patients reported by individual clinics may not necessarily reflect differences in case load between institutions. All participating colposcopy clinics collected digital colposcopy images of all cases recruited. However, the quality of pictures varied substantially between clinics, and robust external review was not feasible.
The software automatically rejects incomplete data sets from benchmarking analyses. Apart from name, date of birth, date of examination, reason for transfer, screening results, and mode of treatment, further obligatory data include adequacy of colposcopy, type of TZ, colposcopy findings, number and results of biopsies, and, in case of excisional treatment, margin involvement. All complete data sets were included in benchmark analyses to compare the overall distribution of TZ types and age-specific distribution between participating colposcopy clinics. Because it is known that TZs change dynamically during a woman’s lifetime, typically with an ectocervical location of the SCJ in younger individuals and an endocervical location in most postmenopausal women, we predefined 3 different age groups: younger than 30 years, between 30 and 50 years, and older than 50 years. The main objective of the study was to identify possible heterogeneities of TZ classification between the 3 age groups among participating centers. Data were compared using 95% confidence intervals (CIs).
A total of 3,723 patients were included in the analysis. Overall, 2,153 cases (58%) were classified as type 2 TZ, 868 (23%) as type 1 TZ, and 702 (19%) as type 3 TZ (see Figure 2). The most frequently reported TZ abnormality in women 50 years or older was type 3 (70%). We found little difference in the distribution of type 3 TZ between colposcopy clinics in this age group; the 95% CIs overlapped in 7 of 8 clinics (see Figure 3I). Similarly, we found little evidence of heterogeneity between the participating clinics in the frequency of type 3 TZ in women younger than 30 years and those aged 30 to 50 years (see Figure 3C and F). Furthermore, the frequency distribution of type 2 TZ in women 50 years or older was similar between centers (see Figure 3H).
In contrast to the relatively homogenous distribution of type 3 TZ, the frequency of types 1 and 2 TZs in women younger than 50 years showed a considerable heterogeneity. Figure 3E shows the 95% CIs for the frequency of type 2 TZs in women aged 30 to 50 years among the participating clinics. Three clinics reported type 2 TZ in 62% to 78% of women aged 30 to 50 years, whereas 4 clinics classified findings as type 2 TZ in less than 50% of cases (see Figure 3E). Similar heterogeneity was observed for type 1 TZ in women younger than 30 years and 30 to 50 years (see Figure 3A and D) and for type 2 TZ in women younger than 30 years (see Figure 3B).
We observed consistent distribution of type 3 TZ among all participating colposcopy clinics in this prospective multicenter study. As expected, type 3 TZ was found in the majority of postmenopausal women, whereas the frequency of this TZ type was evenly low in the age group 30 to 50 years (21%) and rare in those younger than 30 years (5%). It is encouraging that, in this real-life multicenter study, more than 80% of referred patients had TZs classified as type 1 or 2 and were therefore deemed fully satisfactory for colposcopic evaluation.
Participating clinics were not obliged to include all patients in this analysis, but we found no evidence of a selection bias. Data documentation is a time-consuming process, and occasionally, some clinics did not include patients because of lack of available staff resources, but there is no evidence to suggest that subjects were selectively excluded or included on the basis of patient characteristics. Similarly, it is very unlikely that rejection of incomplete data sets by the software caused a bias. This step in the software ensures that the rate of complete documentation is high, and individual clinics are informed automatically about incomplete data sets. Overall, 57% of cases were classified as type 2 TZ. It was the most frequent type in women aged 30 to 50 years and those younger than 30 years (58%). The latter finding is surprising because we expected type 1 TZ to be the most common type in this age group. The heterogeneity in the classification of types 1 and 2 TZs in women younger than 50 years observed between participating clinics is most likely explained by uncertainties about the correct anatomic definition of the endocervical canal. When we discussed reasons for the observed differences among the participating clinics, it became clear that some institutes classified only TZs that were located entirely on the ectocervix and did not approach the external orificium of the cervical canal as type 1, whereas others defined any TZ without endocervical involvement as type 1. The area of uncertainty between types 1 and 2 TZ is marked with a circle in Figure 4. On the basis of such uncertainty, it could be argued that a 2-tier classification could be preferred to the 3-tier IFCPC classification. This concept is analogous to the classification of CIN, which was revised from a 3- to a 2-grade classification because of the low reproducibility of CIN 2. However, all participating colposcopists agreed that classification of TZ according to the 3 types defined by the IFCPC results in a more thorough colposcopic evaluation and a more appropriate excisional therapy compared with the simple judgment about whether or not the SCJ is fully visible. We propose a more precise definition of the external os to improve the utility of the new IFCPC classification. As shown in Figure 4, we propose that the external os is defined as the beginning of the endocervical canal and demarcates the ectocervix and endocervix. The external os is marked by the bold red line in Figure 4. In nulliparous and postmenopausal women, the external os is usually easily recognizable as the narrow opening of the endocervical canal. In these cases, type 2 TZ can usually be recognized only by endocervical evaluation with endocervical specula or other instruments. In premenopausal women who have given birth to 1 or more children vaginally, the external os may be relatively wide and, therefore, it is more difficult to define the narrowest point of the cervical lips. Furthermore, when the SCJ is near, it may be confused with the os itself. We therefore recommend: first, defining the external os; and second, locating the SCJ.
This multicenter analysis of real-life data showed that independent electronic quality assessment of colposcopy clinics is feasible and that the classification of TZ in 3 types improved reporting of colposcopic procedures. Furthermore, we found that the majority of referred patients had type 1 or 2 TZ and were fully eligible for colposcopic evaluation, which underlines the utility of colposcopy in daily practice. However, while the distribution of type 3 TZ between different age groups was homogenous among participating colposcopy clinics, we observed significant heterogeneity in the classification of types 1 and 2 TZ. A more precise anatomic distinction between types 1 and 2 TZ in the IFCPC terminology could clarify this issue and lead to standardized universal reporting of colposcopy findings.
1. Herfs M, Yamamoto Y, Laury A, Wang X, Nucci MR, Laughlin-Drubin ME, et al. A discrete population of squamocolumnar junction cells implicated in the pathogenesis of cervical cancer. Proc Natl Acad Sci U S A
2012; 109: 10516–21.
2. Walker P, Dexeus S, De PG, Barrasso R, Campion M, Girardi F, et al. International terminology of colposcopy
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Keywords:Copyright © 2015 by the American Society for Colposcopy and Cervical Pathology
colposcopy; transformation zone; screening