Abstract
The objective of this study was to determine the diagnostic accuracy of pap smear and colposcopy in detecting the premalignant and malignant lesion of the cervix. In this cross-sectional study, a total number of 160 women who presented with abnormal clinical problem or routine checkup during a 6-month period were included. All the patients underwent pap smear and colposcopy by the same gynecologists team, and finally, cervical biopsy was performed in all the individuals. The demographic and clinical characteristics as well as the obstetrics history were recorded. The diagnostic accuracy of each test was calculated according to the biopsy as gold standard. The sensitivity, specificity, positive predictive value (PPV), and negative predictive values (NPV) were recorded and compared between two modalities. Overall, we included a total number of 160 patients with mean age of 37.6 ± 7.32 (ranging from 24 to 63) years. The sensitivity and specificity of pap smear were found to be 47.19% and 64.79%, respectively. The PPV and NPV of the pap smear were calculated to be 88.69% and 38.46%, respectively. The sensitivity and specificity, PPV, and NPV of the colposcopy were calculated as 64.72%, 52.74%, 76.32%, and 95.41%, respectively. The overall diagnostic accuracy of the pap smear and colposcopy was reported to be 82.2% and 96.3%, respectively. The results of this study demonstrate that colposcopy has a higher diagnostic accuracy in detecting cervical premalignant and malignant lesions compared to the pap smear.
Keywords: Colposcopy, Pap smear, Pathology, Cervix, Premalignant lesions
Introduction
Cancer of the cervix is considered the second mostly diagnosed cancer in women. According to the 2018 global statistics, 569,847 new cases are diagnosed annually of whom 311,365 die due to the cancer itself [1]. The incidence and mortality are increasing worldwide gradually which is associated with increased social and economic burden along with years of life lost [2]. The cervical cancer most important risk factors has been reported to be the human papilloma virus (HPV) infection which is a very common infection in sexually active women [3, 4]. The cervical cancer can be prevented or diagnosed in early stages via the routine and structured screening programs of the cervical cytology [5, 6]. In addition, introduction and application of HPV vaccination programs have resulted in decreased rate and mortality rates of the cervical cancer in recent year in specific age groups [7].
Papanicolao (Pap) smear remains the most available, feasible, and cost-effective tool for screening of the cervix premalignant and malignant lesions [8]. Via the pap smear, several premalignant lesion of the cervix including the cervical dysplasia and inflammatory lesion could be diagnosed in early stage of the disease. However, the accuracy of the pap smear has been reported to range between 53 and 78% between various studies with the same method of interpretation [9–11]. The sensitivity and specificity of the pap smear in detecting high-grade lesions of the cervical intraepithelial neoplasia (CINII and CINIII) have been shown to be 55.4 and 96.8%, respectively [12, 13]. The colposcopy is another screening tool for premalignant lesion of the cervix which is not available in all the centers and is expensive [14]. Those with abnormal pap smear results should undergo the colposcopy to confirm the result [15, 16]. But the gold standard for diagnosis of the cervical premalignant lesion remains the biopsy and histopathological examination [17]. The cervical biopsy is an invasive procedure being associated with some complications including the pain, bleeding, and fibrosis [18]. Thus, there is a trend toward developing high accuracy appropriate non-invasive screening tools for early diagnosis of the cervical premalignant lesions. The diagnostic accuracy of the pap smear and the colposcopy depends on the physician expertise as well as the appropriate technical issues [14, 15]. Several studies have evaluated the diagnostic accuracy of these tests in order to determine the best screening modality in these patient groups [8–10, 12, 14–16]. However, data from Iranian population is scarce. There are limited cumulative studies evaluating and comparing the diagnostic accuracy of pap smear and colposcopy with reference to biopsy in evaluating the premalignant lesion of the cervix [14, 15]. Thus, the aim of the current study was to determine and compare the diagnostic accuracy of the pap smear and the colposcopy in detecting the premalignant lesions of the cervix in a groups of Iranian women considering the cervical biopsy as the gold standard.
Materials and Methods
Study Population
This cross-sectional study was conducted during a 6-month period from March to August 2015, in Shahid Motahari oncology clinic, a tertiary healthcare center affiliated with Shiraz University of Medical Sciences in Southern Iran. We have included a consecutive sample of Iranian women with clinical problem of cervical lesions including abnormal bleeding, pain, postcoital bleeding, and chronic cervicitis or routine checkup who were referred to our clinic for pap smear, colposcopy, and evaluation of the cervical premalignant lesions. We included women between 20 and 60 years of age, non-pregnant, and those who had abnormal clinical findings. Those with active cervical infections, chronic pelvic disorders, pregnant patients, history of previously treated malignant, or premalignant cervical lesion confirmed cervical cancer, and previous history of any other malignancy was excluded from the study. The study was designed and the manuscript was perpetrated and written according to the Standards for the Reporting of Diagnostic accuracy studies (STARD). The study protocol was approved by the institutional review board and medical ethics committee of Shiraz University of Medical Sciences. All the patients provided their informed written consents before inclusion in the study.
Study Protocol
All the patients were examined by a gynecologic oncology fellow and all the positive findings of the history and physical examination were recorded into a data gathering form. The baseline characteristics included demographics (age, ethnicity), obstetrics history (gravid, parity, abortion, live), number of sexual partners, and comorbidities were recorded. All the patients underwent pap smear, colposcopy, and cervical biopsy, in the same visit. All the pap smear examinations were performed according to the standard protocol and the samples were sent to the same laboratory for analysis and report. All the colposcopy examinations were conducted by an attending gynecologic oncologist who was blinded regarding the findings of the pap smear and the clinical findings. After a pelvic examination, cervix was stained with acetic acid 3–5% and then colposcopy was done. Colposcopy findings were divided to low- and high-grade lesion according to acetowhite change, coarse punctation, and mosaic or atypical vessels. Directed biopsy was performed under colposcopy, and the specimens were sent to pathology for histopathological examination. The gold standard for diagnosis of the premalignant and malignant lesions of the cervix was considered to be the gold standard of diagnosis. The results of the pap smear and colposcopy were compared to the results of the histopathological examination. All the histopathological examinations were performed by a same pathologist who was blinded to the results of the pap smear, colposcopy, and the clinical examination of the patients. The histopathological examinations were performed in Shahid Faghihi laboratory according to the standard protocols. The samples were paraffin embedded and stained with hematoxylin and eosin. They were studied and reported according to the WHO protocol.
Statistical Analysis
The sample size was calculated according to the n = Z2pq/d2 formula which is based on the binominal distribution. In this formula, n stands for minimum required population and p represents the attributable accuracy of TVU and q = 1–p. The p was considered to be 0.76 according to a previous study [1]. The precision of the estimates, d, was set at 5%, and Z (the normal deviate) was given a value of 1.96. In solving this formula for n, it was shown that 154 individuals were needed for the study. In order to compensate for non-evaluable patients, we included 160 women with abnormal pap smear results.
All statistical analyses were performed with the Statistical Package for Social Sciences version 18.0 (SPSS Inc., Chicago, Ill., USA). The results are expressed as mean value ± standard deviation (SD) or proportions. The histopathology of the cervix was considered as the gold standard for the diagnosis of endometrium abnormalities. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of pap smear and colposcopy were calculated on the basis of pathologic reports. Receiver-operating characteristics (ROC) curve was prepared (plot of sensitivity vs. one specificity) and the areas under the curves (AUC) estimated. AUC = 1 indicates a perfect test, AUC > 0.9 indicates high accuracy, and AUC between 0.7 and 0.9 indicates moderate accuracy [19].
Results
Overall, we included a total number of 160 patients with abnormal clinical findings or routine checkup who were referred to our center for pap smear, colposcopy, and biopsy during the study period. The mean age of the included patients was 37.6 ± 7.32 (ranging from 24 to 63) years. Most of the patients had one sexual partner at the time of inclusion, and most (80.6%) were multigravid. Approximately, half of the patients (49.4%) were coming from urban areas and most of them (78.1%) were households. Among the patients, there were 41 (25.6%) passive smokers and 7 (4.4%) active smokers. None of the patients have received HPV vaccination before inclusion in the study. The baseline demographic and clinical characteristics of the patients are summarized in Table 1.
Table 1.
The baseline characteristics of 160 women with abnormal clinical signs or those who referred for routine check-ups included in the current study
| Variable | Value |
|---|---|
| Age (years) | 37.64 ± 7.32 |
| No. of sexual partners | 0.97 ± 0.28 |
| Gravid | 2.92 ± 1.74 |
| Primigravid (%) | 31 (19.4%) |
| Multigravid (%) | 129 (80.6%) |
| Live | 2.71 ± 1.68 |
| 1 (%) | 31 (19.4%) |
| 2 (%) | 55 (34.4%) |
| ≥ 3 (%) | 74 (53.8%) |
| Abortion | 0.21 ± 0.45 |
| 0 (%) | 130 (81.3%) |
| 1 (%) | 27 (16.9%) |
| 2 (%) | 3 (1.9%) |
| Location | |
| Urban (%) | 79 (49.4%) |
| Rural (%) | 81 (50.5%) |
| Job | |
| Housewife (%) | 125 (78.1%) |
| Employee (%) | 35 (21.9%) |
| Smoking | |
| Passive (%) | 41 (25.6%) |
| Active (%) | 7 (4.4%) |
The most common clinical symptom was the postcoital bleeding being reported in 27 (16.9%) of the patients while only 27 (16.9%) patients had history of genital warts. About 46 (28.8%) had vaginosis and 94 (58.8%) did not have any vaginal infection. The pap smear results were positive 93 (58.1%) patients while colposcopy was found to be abnormal in 91 (56.9%) patients. The results of biopsy and histopathology examination revealed 72 (45.0%) positive and 88 (55.0%) negative results. The detailed results of each diagnostic study are summarized in Table 2.
Table 2.
Clinical and laboratory findings of the 160 patients included in the current study
| Variable | Value |
|---|---|
| Postcoital bleeding (%) | 27 (16.9%) |
| History of wart (%) | 27 (16.9%) |
| Genital infection | |
| Negative (%) | 94 (58.8%) |
| Vaginosis (%) | 46 (28.8%) |
| Cervix (%) | 20 (12.5%) |
| Pap smear | |
| Normal (%) | 93 (58.1%) |
| Abnormal (%) | 67 (41.9%) |
| Colposcopy | |
| Normal (%) | 69 (43.1%) |
| Abnormal (%) | 91 (56.9%) |
| Pathology | |
| Normal (%) | 72 (45.0%) |
| Abnormal (%) | 88 (55.0%) |
| Pap smear findings | |
| Normal (%) | 93 (58.1%) |
| ASCUS (%) | 32 (20.0%) |
| LSIL (%) | 17 (10.6%) |
| HSIL (%) | 7 (4.4%) |
| AGUS (%) | 11 (6.98%) |
| Colposcopy findings | |
| Normal (%) | 69 (43.2%) |
| Low-grade lesion (%) | 60 (37.5%) |
| High-resolution lesion (%) | 24 (15.0%) |
| Invasive cancer (%) | 7 (4.3%) |
| Pathology findings | |
| Normal (%) | 72 (45.0%) |
| CIN I (%) | 48 (30.0%) |
| CIN II (%) | 25 (15.6%) |
| CIN III (%) | 12 (7.5%) |
| Invasive (%) | 3 (1.9%) |
The diagnostic accuracy of the pap smear and colposcopy was evaluated based on the histopathological results (gold standard). The sensitivity and specificity of pap smear were found to be 47.19% and 64.79%, respectively. In the same way, the PPV and NPV of the pap smear were calculated to be 88.69% and 38.46%, respectively. The overall diagnostic accuracy of the pap smear was found to be 82.2%. The sensitivity and specificity of the colposcopy were calculated as 64.72% and 52.74%, respectively. In the same way, the PPV and NPV of the colposcopy were calculated to be 76.32% and 95.41%, respectively. The overall diagnostic accuracy of the colposcopy for detection of the cervical premalignant lesion was found to be 96.3% (Table 3). We also found that the findings of the pap smear (p = 0.002) and the colposcopy (p < 0.001) significantly were correlated with the histopathological examination. The results of colposcopy and pap smear were also correlated with each other statistically (p < 0.001).
Table 3.
The diagnostic accuracy of pap smear and colposcopy in diagnosis of premalignant lesion of the cervix in a series of 160 patients with clinical findings or routine check-up
| Sensitivity | Specificity | PPV | NPV | Accuracy | |
|---|---|---|---|---|---|
| Pap smear | 47.19% | 64.79% | 88.69% | 37.46% | 82.2% |
| Colposcopy | 64.72% | 52.74% | 76.32% | 95.41% | 96.3% |
Discussion
The diagnostic accuracy of the different modalities for diagnosis of malignant and premalignant lesion of the cervix has been the matter of several research and controversies [9, 10, 14]. Although several studies have compared the diagnostic accuracy of these diagnostic methods, however, the consensus regarding the best diagnostic modality is still a matter of research. In the current study, we have performed a comparison between pap smear and the colposcopy for diagnosis of premalignant and malignant lesions of the cervix. We found that the diagnostic accuracy of the colposcopy is higher than pap smear being defined by higher sensitivity and higher NPV. The overall diagnostic accuracy of the colposcopy was also significantly higher than that of pap smear (96.3% vs. 82.2%). Thus, based on the results of the current study, we can indicate that colposcopy is superior to pap smear in detecting the malignant and premalignant lesions of the cervix.
We found that atypical squamous cells of undetermined significance (ASCUS) were reported in 31 (19.3%) patients which is in concordance with previous reports [15, 16, 20]. On the other hand, colposcopy demonstrated that low-grade and high-grade lesions were presented in 41 (25.6%) and 28 (17.5%) patients, respectively. These findings are in line with the results from previous studies [21, 22]. In histopathological examination, the CIN1 were found to be the most common finding which is also in accordance with previous reports [9, 14, 15]. However, our patient population had a higher rate of AGUS which was reported to be 11 (6.98%) and is higher when compared to the other series [23].
In a recent study, Karimi-Zarchi et al. [15] compared the diagnostic accuracy of the pap smear, colposcopy, and the liquid-based cytology (LBC) in diagnosis of the cervical malignant and premalignant lesions. They reported that the sensitivity, specificity, PPV, and NPV and accuracy of conventional pap smear were 51%, 66.6%, 96%, 8%, and 92%, respectively. In the same way, the sensitivity, specificity, PPV, NPV, and accuracy of LBC were found to be 55.3%, 77.7%, 97.5%, 10%, and 56.6%, respectively. About the colposcopy, sensitivity was 70.9%, specificity was 44.4%, PPV was 95.2%, NPV was 8.8%, and accuracy was 69.3%. They concluded that the colposcopy has the best efficacy in detecting any cervical lesion when compared with any other diagnostic technique [15]. Previously, Cheung et al. [24] reported that LBC method was superior to detect squamous intraepithelial lesion (SIL) lesions (5.1% vs. 3.5%) especially high-grade squamous intraepithelial lesion (HSIL) compared to the conventional pap smear (1% vs. 0.5%). They also reported that detecting the ASCUS and low-grade squamous intraepithelial lesion (LSIL) was lower in LBC than the conventional pap smear and LBC demonstrated no change in detecting the lesions of SCC, adenocarcinoma, and HSIL compared to the conventional pap smear method [24]. Recently, Nkwabong et al. [16] performed a diagnostic accuracy study to compare the pap smear to biopsy in detecting the premalignant lesion of the cervix. They included a total number of 231 women. The sensitivity, specificity, PPV, and NPV values of Pap smear were 55.5%, 75%, 88.2%, and 33.3%, respectively [16]. They also reported a low sensitivity for the pap smear as demonstrated by our study. These demonstrate that pap smear has low sensitivity but acceptable specificity in detecting the cervical premalignant lesions. Thus, a complementary test such as the colposcopy or biopsy should accompany the pap smear in order to increase the diagnostic accuracy.
We note some limitations to our study. First, we included a limited number of patients. Our study population was limited as this was caused by the limited resources in our series and centers. However, the study has 80% power to detect the appropriate diagnostic accuracy in each diagnostic modality. The other limitation of the study was the lack of including other diagnostic modalities such as LBC in this series. This could help us on commenting on the other available diagnostic modalities when screening for the cervical malignant lesions. Overall, this is among the only available studies from Iran, determining and comparing the diagnostic accuracy of several modalities in screening for cervical malignant and premalignant lesions.
Conclusion
In conclusion, the results of this study demonstrate that colposcopy has a higher diagnostic accuracy in detecting cervical premalignant lesions compared to the pap smear. Since cervical cancer is the most common gynecological cancer in developing countries, colposcopy is recommended for screening of the cervical malignant and premalignant lesions.
Acknowledgments
We would like to thank all the patients and their families who patiently participated in the current study. We would also like to acknowledge the editorial assistance of the Diba Negar Research Institute for improving the English and style of the manuscript.
Funding Information
This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
Compliance with Ethical Standards
Conflict of Interest
The authors declare that they have no conflict of interest.
Ethical Approval
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional review board and medical ethics committee of Shiraz University of Medical Sciences and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Informed Consent
Informed consent was obtained from all individual participants included in the study.
Footnotes
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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