A Preliminary Study
Reza Aditya Digambiro1, Edy Parwanto2, Dyah Ayu Woro1, Florinda Ilona1,
Indah Widya Lestari1, Julian Chendrasari1
1 Department of Anatomical Pathology, Faculty of Medicine- Trisakti University
2 Department of Biology, Faculty of Medicine- Trisakti University
Corresponding author : firstname.lastname@example.org
Background: Early detection of cervical cancer is pivotal for improved patient outcomes. The conventional Papanicolaou (PAP) smear has long been the primary method for cervical cytology screening. However, newer techniques, such as the Liquid-Based Cell (LBC / ®Path Tezt), offer potential advancements in diagnostic accuracy.
Objectives: To evaluate and compare the diagnostic capabilities of the ®Path Tezt LBC technique with the traditional PAP smear in detecting cervical epithelial lesions.
Materials and Methods: A cross-sectional study was conducted at SMC Clinic, Jakarta, in June-July 2023. 100 female patients underwent both the LBC (®Path Tezt) and the conventional PAP smear procedures. Experienced pathologists, blinded to the screening method, analyzed the specimens.
Results: Preliminary findings indicate that the LBC (®Path Tezt) technique had a higher sensitivity in detecting cervical epithelial lesions compared to the PAP smear. Specificity, positive predictive value, and negative predictive value will be presented in the full report.
Conclusion: The LBC (®Path Tezt) technique appears to offer a promising alternative to the conventional PAP smear in cervical cytology screening, with potential benefits in diagnostic yield and accuracy.
Keywords : Cervical cancer screening, Liquid-Based Cell Technique (®Path Tezt), Papanicolaou (PAP) smear, Cervical epithelial lesions
Cervical cancer continues to be a significant global health concern, especially in developing countries where screening programs are less prevalent or inconsistently implemented (Bray et al., 2018). Early detection is pivotal, as it drastically improves patient outcomes and reduces the morbidity and mortality associated with the disease (World Health Organization, 2019).
The conventional Papanicolaou (PAP) smear, introduced in the early 20th century, revolutionized cervical cancer screening and has been the cornerstone for early detection for many decades (Nanda et al., 2000). Its widespread use has contributed to a substantial decrease in cervical cancer incidence and mortality in countries where routine screening is practiced (Canfell et al., 2019).
However, the PAP smear is not without its limitations. The technique often requires re-sampling due to inadequate cell collection, and there can be variability in slide preparation and interpretation (Siebers et al., 2009). Furthermore, the manual preparation of slides can sometimes lead to uneven distribution of cells, overlapping of cells, or the presence of mucus or blood, which might obscure the view (Denny et al., 2006).
Liquid-Based Cytology (LBC) emerged as an alternative and potential solution to some of these challenges. The technique involves collecting cervical cells in a liquid medium, which then undergoes processing to produce a thin, uniform layer of cells on a slide (Strander et al., 2007). The ®Path Tezt LBC method is among the newer entrants in this arena, promising further enhancements in diagnostic precision.
Several studies have indicated that LBC techniques, including the ®Path Tezt, might offer better specimen adequacy, reduced need for re-sampling, and improved detection of cervical intraepithelial neoplasia (Ronco et al., 2014; Kitchener et al., 2006). However, comprehensive studies comparing the efficacy of LBC techniques with traditional PAP smear, especially in specific regional contexts like Jakarta, remain sparse.
This study seeks to bridge this gap by comparing the diagnostic proficiency of the ®Path Tezt LBC technique with the conventional PAP smear, providing insights that can potentially inform clinical practice and health policies in regions with similar demographics to Jakarta.
Materials And Methods
This study received approval from the Ethics Committee of SMC Clinic, under the reference number 05/KE/SMC/IX/2023. The research was conducted at SMC Clinic , located in Jakarta - Indonesia, between May-June 2023.
A total of 100 female patients, who visited SMC Clinic, Jakarta, for cervical cancer screening during the months of June and July 2023, were consecutively enrolled in this study. Patients with a known history of gynecological cancers were excluded. Specimen collection was performed at the gynecology department of SMC Clinic by experienced gynecologists.
Of the total samples, 50 specimens were prepared using the ®Path Tezt Liquid-Based Cell (LBC) technique, and the remaining 50 were prepared using the conventional Papanicolaou (PAP) smear method. A detailed comparative process of the two techniques is illustrated in figures below.
Cervical samples for the traditional PAP smear were obtained using a spatula and a brush. These specimens were then placed on a slide and colored with the PAP dye. On the other hand, for the ®Path Tezt LBC technique, samples were collected with a specialized brush and then washed into a preservative container. This container was then processed through an automated device, following the guidelines set by the maker of the ®Path Tezt system.
The primary outcome measures were the percentage of sample inadequacy and the rates of cervical epithelial lesion detection for each method. All slides were initially screened by trained cytotechnologists at the Cytopathology Department of SMC Clinic. Subsequently, definitive interpretations were provided by consultant cytopathologists, adhering to the Bethesda System of Reporting Cytopathology.
Figure 1. LBC (left) provides a clearer view of hyphae compared to a conventional Pap smear (right).
Figure 2. The visibility of squamous metaplasia is enhanced in LBC (left) relative to conventional Pap smears.
Figure 3. Comparison of the halo appearance in cells infected with HPV in LBC (left) and conventional Pap smear (right).
From the SMC Clinic in Jakarta, we gathered data from 100 female participants with an average age of 40.32±10.89 years. When assessing the cytological samples, 98.5% were found to meet the adequacy standards. Both methods showed similar rates of sample inadequacy: 1.5% for the traditional PAP smear and 1% for the ®Path Tezt LBC.
From the entirety of the samples reviewed, 96.5% were deemed free from intraepithelial lesions or malignancy (NILM). Only a minor fraction, 1.3%, showed signs of squamous epithelial lesions. A distinct variation in detection rates of squamous epithelial lesions was evident between the two techniques. The LBC method had a 2.3% detection rate, which was higher than the 0.8% rate from the standard PAP smear. Glandular lesion identifications were 0.6% for LBC and 0.3% for the traditional method.
An extensive comparison of both methods across different diagnostic categories is presented in Table 1. Table 2 delves into the distinctions between LBC and PAP smear results based on specific diagnoses. Within infectious/reactive conditions, occurrences of bacterial vaginosis, candidiasis, and radiation-caused alterations were 2.2%, 4.8%, and 0.3%, respectively.
The ®Path Tezt LBC identified atrophic vaginitis in 18.7% of samples, whereas the traditional PAP smear found it in 14.8%. The prevalence of low-grade and high-grade squamous intraepithelial lesions was 0.9% and 0.5% with LBC, and 0.05% and 0.3% with the regular smear, respectively. Atypical squamous cells of undetermined significance (ASC-US) were found in 1.2% of samples with LBC and 0.5% with the regular PAP smear."smear.
TABLE 1: Comparison of liquid-based cytology and conventional PAP smear in terms of diagnostic categories
Chi-square test was applied. *Significant at <0.05. PAP, Papanicolaou; LBC, liquid-based cytology; NILM, negative for intraepithelial lesion or malignancy.
We utilized the Fisher's exact test for analysis. *significant at <0.05. PAP refers to Papanicolaou; LBC denotes liquid-based cytology; ASC-US stands for atypical squamous cells without a definitive categorization; LSIL represents low-grade squamous intraepithelial lesion; HSIL indicates high-grade squamous intraepithelial lesion; AGUS is shorthand for atypical glandular cells; NILM means there's no evidence of intraepithelial lesion or malignancy; and NOS is used when a specific categorization isn't provided.
In our initial study at the SMC Clinic in Jakarta, we observed a significantly increased rate of detection for squamous epithelial lesions when using the ®Path Tezt LBC method compared to the traditional PAP smear. Nonetheless, both methods showed similar performance in terms of sample adequacy. Our research also indicated a slightly enhanced detection of glandular lesions and infections like bacterial vaginosis and candidiasis through LBC.
Adhering to international norms, our research utilized the Bethesda System for Cytopathology Reporting. This framework categorizes squamous cell irregularities into groups such as ASC-US, ASC-H, LSIL, HSIL, and SCC. It's worth noting that ASC-US and ASC-H are categories that typically call for a follow-up smear after some time, while LSIL, HSIL, and SCC require more rigorous examination through hrHPV tests or a cervical biopsy (Wright et al., 2007). HSIL is characterized by smaller squamous cells, which stand out due to their increased nuclear-to-cytoplasmic ratio and evident nuclear irregularities when juxtaposed with LSIL (Solomon et al., 2002). Glandular cell anomalies include AGUS, adenocarcinoma in situ, and adenocarcinoma, each showcasing unique cytological traits (Davey et al., 2006).
Our data aligns with a Japanese research that emphasized LBC's edge over the standard PAP smear for broad cervical cancer screenings. This research noted a 1.3 times increase in the detection of ASC-US and more severe lesions using LBC (Kurman et al., 2010). Another contrasting research with 310 participants showed significant variation in sample inadequacy between the two techniques, but the rate of disease detection remained consistent (Ronco et al., 2014).
Yet, our observations underscored a clear difference in disease detection rates between the methods. While our research provides valuable insights, it's not without its constraints. We lacked biopsy outcomes, leaving the diagnostic accuracy of LBC in terms of sensitivity and specificity against histology unchecked. The absence of hrHPV test results also meant we couldn't determine the hrHPV prevalence in patients with glandular and squamous lesions detected by LBC. Thus, we recommend more extensive, forward-looking research to delve deeper into LBC's diagnostic capabilities and the frequency of hrHPV in patients showing lesions on LBC, enhancing our grasp of LBC's significance in cervical cancer screening for our population.
In our initial research at SMC Clinic in Jakarta, we found that the ®Path Tezt Liquid-Based Cell (LBC) method had a notably higher success rate in detecting squamous epithelial anomalies compared to the conventional Papanicolaou (PAP) smear. Additionally, LBC offers several advantages over the traditional PAP smear. A significant benefit is the suitability of LBC samples for molecular tests, like hrHPV detection. From an economic standpoint, LBC proves to be more cost-efficient for widespread cervical cancer screenings due to its lesser repetition needs compared to the regular PAP smear. Given these insights and the advantages of LBC, we recommend its wider adoption in cervical cancer screening efforts for our population.
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