Objective
The objective of the study was to assess the screening history of women with cervical cancer and review normal cervical smears 5 years preceding the diagnosis.
Study Design
Cytological and histological results of 401 women treated for invasive cervical cancer between 1991 and 2008 at the Radboud University Nijmegen Medical Center were studied. Ninety-eight normal smears were reviewed.
Results
Of the 401 women, 269 (67%) received at least 1 invitation for the national screening program for cervical cancer (NCSP). One- third fell outside the target age of the NCSP. Seventeen percent never responded to the invitation(s). Twenty-one percent had 1 or more normal smears within 5 years preceding the diagnosis. After review, only 39% of those smears were reviewed as a normal smear.
Conclusion
Half of the women with cervical cancer were never screened because of the limited target age range or nonattendance. Twenty-one percent had a normal smear within 5 years preceding the diagnosis, caused by interpretation and/or sampling errors.
A national screening program for cervical cancer (NCSP) was introduced in The Netherlands in 1988. Women between the ages of 35 and 53 years were invited for a cervical smear every 3 years. The NCSP was reorganized in 1996 to improve the effectiveness and efficiency of the screening. Therefore, the age range of the target population was extended to 30-60 years, and the screening interval increased from 3 to 5 years. From 1990 to 2006, the incidence and mortality rate for cervical cancer in The Netherlands decreased by 28% and 42%, respectively.
Despite organized screening in The Netherlands, around 600-700 women are still diagnosed with cervical cancer annually. Factors influencing these numbers are the target age range of the screening program, the frequency of screening, and nonattendance to the screening program. Important factors in women diagnosed with cervical cancer despite adequate screening are problems with sampling, interpretation, and consistent clinical follow-up. However, a small number of rapidly developing cancers (interval cancers) cannot be ruled out.
The Papanicolaou smear has been a remarkably effective tool in cancer prevention. However, cytological smears have been associated with a significant rate of sampling and/or interpretation errors, resulting in a sensitivity of approximately 60-70%. False-negative results may have a great impact because cervical abnormalities might be missed and therefore left untreated. Smears within normal limits (WNL) preceding cervical cancer and confirmed by cytological review may be either an indication for a sampling error or suggestive for a rapidly progressive form of cervical cancer. A study of WNL smears preceding cervical cancer may show to what extent improving interventions might be possible.
The aim of this study was to determine how many women diagnosed with cervical cancer in the Nijmegen region had been screened according to the national guidelines and, if screened properly, why screening did not prevent these cases?
Materials and Methods
Data collection
Between 1991 and 2008, 421 women were diagnosed with invasive cervical cancer and treated at the Radboud University Nijmegen Medical Center (RUNMC), Nijmegen, The Netherlands. Data concerning cervical cytology and histology were retrieved from the Dutch nationwide registry of histo- and cytopathology (PALGA). This database has national coverage from 1991 onward, enclosing all surgical specimens and cervical smears ever taken from each patient, both by the general practitioner and medical specialists. Twenty patients who were initially diagnosed in a foreign country or had incomplete data were excluded, leaving 401 patients opting for evaluation.
The cytological results were registered according to the diagnostic categories of Papanicolaou and/or CISOE-A (Composition, Inflammation, Squamous epithelium, Other and endometrium, Endocervical columnar epithelium, Adequacy of the smear), which is easily translatable to the Bethesda 2001 (TBS 2001) classification. Only cytological smears performed within the framework of the screening program were registered. Diagnostic smears leading to the diagnosis of cervical cancer, performed as a consequence of symptoms, were not included. Analysis has focused on smears within the screening program, prior to the diagnosis.
Patient and tumor characteristics (eg, stage/type) were obtained from the hospital medical records. All histological types were included in our analysis to properly evaluate the current screening program. According to the date of birth, we assessed whether women had ever been invited for the national screening program. Women within the age category of the national screening program constituted our target group for further study. They had been invited at least once.
Women who were younger or older than the target cohorts were not further analyzed with respect to their screening history because the aim of the study was to evaluate women who were eligible for cervical cancer screening.
In the collected data, women were scored as regularly screened, irregularly screened, or never screened. A patient was scored as regularly screened when screened according to the guidelines of the national screening program on cervical cancer (responded to all invitations of the national screening program, every 5 years from the age of 30 years until 60 years). A deviation in screening interval of 10% was accepted. Patients were scored as never screened if they never had a smear taken (nonresponders). Otherwise, the patients were scored as irregularly screened. This group responded to at least 1 of the invitations of the screening program but not to all, or the frequency and/or timing was not adequate (interval longer than 5 years).
All normal cervical smears within 5 years before the diagnosis of cervical cancer were requested from pathology laboratories around the country. All smears were made anonymous before sending them to 2 expert cytotechnologists (CTs) (M.R.J.S.-v.d.P. and J.E.M.V.) for review. Both CTs scrutinized the smears for abnormal cells with full knowledge of the study, using a review protocol, noting the CISOE-A classification, the quantity and nature of the cells, and the extent of certainty about their judgment. The aim was not to repeat a normal screening setting but to scrutinize the smears for abnormal cells to distinguish interpretation errors from sampling errors/progressive forms of cancer.
After an extensive search for abnormal cells, all cervical smears were provided with a new diagnosis, according to the 2001 Bethesda System. In case the judgments of the 2 CTs were discordant, they reassessed the smear together and came to concordance.
Statistical analysis
The Statistical Package for Social Sciences (SPSS version 16.0; SPSS, Chicago, IL) was used to perform the analyses. Patient characteristics and tumor characteristics were compared using nonparametrical tests (χ 2 and Mann-Whitney). We considered P ≤ .05 as statistically significant.
The study was exempt from institutional review board approval because data were gathered retrospectively and subsequently made anonymous.
Results
Of the 401 eligible women, 269 (67%) had been invited at least once for participation in the national screening program (target cohorts). A number of 87 women (22%) exceeded the age limit to be invited for the NCSP (older than target cohorts), and 45 (11%) were younger than the starting age of the NCSP when diagnosed with cervical cancer (younger than target cohorts) ( Figure 1 ).
