Cervical cancer is the fourth most common malignancy among women globally, with a significant burden in low- and middle-income countries such as India【1】. Early detection through cytological screening programs has proven to significantly reduce morbidity and mortality associated with this preventable disease【2】.

The Papanicolaou (Pap) smear has long been the cornerstone of cervical cancer screening. However, limitations such as inadequate sampling, obscuring blood or inflammation, and uneven smear distribution have led to the evolution of newer techniques such as liquid-based cytology (LBC)【3】.

LBC offers several advantages over conventional smears, including improved sample adequacy, reduction in unsatisfactory smears, and the ability to perform ancillary testing such as HPV DNA analysis from the residual sample【4】【5】. International studies have reported higher sensitivity and comparable or slightly lower specificity for LBC compared to conventional Pap smears【6】.

In India, although LBC is increasingly available, it is not yet universally implemented due to cost and infrastructure constraints. Hence, a direct comparison of the two modalities within local resource settings is critical for guiding public health policy and institutional protocols【7】.

The present study aims to compare the diagnostic efficacy of LBC and conventional Pap smear in a cohort of 100 women attending gynaecology services at Burdwan Medical College, with a focus on sample adequacy, cytological abnormalities detected, and diagnostic concordance.

2. Objectives

Primary Objective

The primary objective of the study was to compare the diagnostic performance of Liquid-Based Cytology (LBC) and Conventional Pap Smear (CPS) in cervical cancer screening with respect to the following parameters:

• Sample adequacy
• Detection rates of epithelial cell abnormalities, including atypical squamous cells of undetermined significance (ASC-US), low-grade squamous intraepithelial lesions (LSIL), and high-grade squamous intraepithelial lesions (HSIL)
• Overall diagnostic concordance between the two cytological methods

Secondary Objectives

The secondary objectives were:

• To evaluate the rate of unsatisfactory smears in both techniques
• To assess the background clarity, presence of inflammatory or obscuring elements, and cellular preservation in each method
• To examine the feasibility of implementing LBC as a routine screening tool in a resource-limited government hospital setting

This cross-sectional comparative study was conducted in the Department of Pathology, Burdwan Medical College, over a period of six months from January 2024 to June 2024. A total of 100 women attending the gynaecology outpatient department for routine cervical cancer screening or with related complaints such as abnormal vaginal discharge, post-coital bleeding, or intermenstrual bleeding were included. Each participant underwent both Conventional Pap Smear (CPS) and Liquid-Based Cytology (LBC) sampling during the same visit.

Women between 21 and 65 years of age who provided informed written consent and had an intact cervix were eligible for inclusion. Those who were pregnant, menstruating, had a history of cervical malignancy, or were undergoing active cancer treatment were excluded. Additional exclusion criteria included recent sexual activity, douching, or vaginal medication use within 48 hours, as well as the presence of active cervicovaginal infections at the time of examination.

Cervical samples were collected by trained personnel. The conventional Pap smear was obtained first using an Ayre’s spatula and endocervical brush, with the specimen promptly smeared onto a glass slide, fixed in 95% ethanol, and stained using the Papanicolaou staining method. Subsequently, a second sample was collected with a cytobrush and transferred into a liquid-based cytology vial (SurePath), which was processed using an automated monolayer preparation system according to the manufacturer’s protocol.

All smears were evaluated independently by two experienced cytopathologists who were blinded to each other’s assessments and to the patient’s clinical details. Interpretation was performed using the 2014 Bethesda System for Reporting Cervical Cytology. Parameters analyzed included sample adequacy, epithelial cell abnormalities (such as ASC-US, LSIL, HSIL), glandular changes, and qualitative features like background clarity, inflammatory exudates, and cell preservation.

Statistical analysis was performed using SPSS version 25. Categorical variables were expressed as frequencies and percentages, and compared using the McNemar’s test for paired binary outcomes and Fisher’s exact test when expected cell counts were <5. Cohen’s kappa statistic was used to assess inter-method diagnostic agreement. A p-value < 0.05 was considered statistically significant.

Study Population

Of the 100 women included in the study, the mean age was 38.6 ± 8.4 years, with most patients (67%) attending for routine screening. A minority presented with symptoms such as leukorrhea (20%), post-coital bleeding (8%), and intermenstrual spotting (5%). None had a prior history of cervical intraepithelial neoplasia or cervical surgery. Table 1 summarizes the baseline demographic and clinical profile.

Table 1. Baseline Characteristics of Study Participants

 Sample Adequacy

Liquid-Based Cytology (LBC) showed superior sample adequacy, with 97% satisfactory smears, compared to 85% in Conventional Pap Smear (CPS). This 12% improvement in adequacy was statistically significant (p = 0.004) McNemar’s test, as shown in Table 2. This supports the advantage of LBC in reducing smear rejection due to technical artifacts or obscuring factors.

Table 2. Sample Adequacy: CPS vs. LBC

 Detection of Epithelial Cell Abnormalities

LBC demonstrated a higher detection rate of epithelial abnormalities, particularly ASC-US and LSIL, though these differences were not statistically significant. The detection of HSIL was identical across both techniques (3%). Notably, LBC showed a trend toward greater sensitivity for low-grade lesions, likely due to its cleaner background and better cell preservation. Detailed distributions are shown in Table 3.

Table 3. Detection of Cytological Abnormalities by CPS and LBC

Note: McNemar’s test was applied for paired categorical comparisons; Fisher’s exact test was used when expected frequencies were low.

Diagnostic Concordance

Diagnostic agreement between CPS and LBC was substantial, with an overall Cohen’s kappa value of 0.72 (95% CI: 0.60–0.84). Perfect concordance was observed for HSIL detection (κ = 1.00), while agreement for ASC-US and LSIL ranged from moderate to substantial. These results indicate reasonable overlap between the two methods, with LBC contributing additional diagnostic yield. Concordance values are detailed in Table 4.

Table 4. Diagnostic Concordance between CPS and LBC

 Smear Quality Assessment

LBC consistently outperformed CPS in terms of background clarity, cellularity, and reduced obscuring elements. A clean background was observed in 93% of LBC smears vs. 62% for CPS, while inflammation and haemorrhage were significantly less frequent in LBC (p < 0.001). Adequate cellularity was also higher in LBC (98%) than CPS (86%), reinforcing its technical superiority. See Table 5 for details.

Table 5. Smear Quality Comparison Between CPS and LBC

 Unsatisfactory Smear Analysis

Of the 15 unsatisfactory CPS smears, 40% were due to air-drying artifacts, followed by scant cellularity (33.3%) and obscuring elements (26.7%). In contrast, only 3 LBC smears were unsatisfactory, primarily due to insufficient cellular material. These findings emphasize the technical robustness of LBC, especially in routine screening where smear adequacy directly impacts diagnostic outcomes

This study aimed to compare the diagnostic performance of Liquid-Based Cytology (LBC) and Conventional Pap Smear (CPS) for cervical cancer screening in a cohort of 100 women attending a tertiary care hospital. The findings demonstrate that LBC provides superior sample adequacy, better smear quality, and a higher detection rate for low-grade epithelial abnormalities, consistent with several global and Indian studies.

In our study, LBC achieved a 97% adequacy rate, significantly higher than the 85% adequacy observed with CPS (p = 0.004). This is in line with previous data by Deshpande et al., who reported a 95.2% adequacy rate with LBC compared to 82.1% with CPS in a cohort of 500 women【8】. Similarly, Vaidya et al. found that unsatisfactory smears were reduced by more than 50% using LBC in a community screening setting【9】. Our findings further reinforce that the monolayer preparation and elimination of obscuring artifacts like blood and mucus in LBC contribute to its improved adequacy and diagnostic efficiency.

Smear quality assessment revealed a 93% clean background rate in LBC versus only 62% in CPS (p < 0.001), consistent with findings from Rani et al., who observed similar trends in clarity and inflammatory suppression using LBC【10】. The significant reduction in haemorrhagic and inflammatory interference enhances interpretability, particularly in low-resource settings where repeated sampling may be logistically challenging.

Although the overall rate of epithelial abnormalities detected was modest, LBC showed a higher yield of ASC-US (11%) and LSIL (9%) compared to CPS (7% and 6%, respectively). These findings mirror those of Kaur et al., who reported increased sensitivity for detecting ASC-US and LSIL using LBC, attributing it to enhanced cell dispersion and preservation【11】. Notably, detection of HSIL was identical across both methods (3%), which may reflect the preserved nuclear detail even in conventional smears for high-grade lesions, a finding echoed by studies such as by Sharma et al.【12】.

While the differences in abnormality detection did not reach statistical significance in our cohort, likely due to sample size, the trend toward increased detection in LBC underscores its value in early lesion identification. This is clinically relevant, given the potential for progression from LSIL to high-grade lesions in high-risk HPV-positive women.

The diagnostic concordance between CPS and LBC in our study was substantial, with an overall Cohen’s kappa of 0.72, indicating high reliability. Agreement was strongest for HSIL (κ = 1.00) and NILM (κ = 0.81). Similar levels of concordance were reported by Mehrotra et al., who observed κ values of 0.78 and above when comparing CPS and LBC across various lesion grades【13】. These data support the feasibility of using LBC in routine diagnostic settings without compromising interpretative consistency.

From a statistical standpoint, the 12% improvement in sample adequacy and the 31% relative increase in ASC-US detection with LBC, though not statistically significant in all instances, represent clinically meaningful enhancements. Such numerical improvements gain further importance when scaled to population-level screening, where early identification of premalignant lesions can significantly reduce cervical cancer incidence【14】. Moreover, the reduced need for repeat sampling in LBC minimizes patient anxiety, follow-up loss, and resource utilization.

While LBC has a higher per-test cost, the reduced rate of unsatisfactory smears, improved clarity, and potential for HPV co-testing make it a cost-effective option in the long term, especially in high-volume public health facilities【15】. Our findings support its integration into national screening programs, particularly as Indian health policy gradually transitions to HPV-based algorithms with cytology triage.

 Limitations

This study had several limitations. First, the sample size was relatively small and drawn from a single tertiary care centre, which may limit the generalizability of the findings to the broader population. Second, although the same patients underwent both LBC and CPS sampling, inter-observer variability in cytological interpretation, though minimized by blinding, could still influence diagnostic outcomes. Third, histopathological confirmation was not universally available for all abnormal cytology results, limiting our ability to directly assess the true sensitivity and specificity of each method. Lastly, cost-effectiveness analysis was not included in this study, which is an important consideration in low-resource public healthcare settings.

In this comparative study, Liquid-Based Cytology (LBC) demonstrated significantly better sample adequacy, superior smear quality, and a trend toward higher detection of low-grade epithelial abnormalities compared to Conventional Pap Smear (CPS). The overall diagnostic concordance between the two methods was substantial, particularly for high-grade lesions. These findings support the potential integration of LBC into routine cervical cancer screening programs, especially where resources and infrastructure allow.

However, further large-scale, multi-centre studies with histopathological correlation and cost-benefit analyses are recommended before widespread adoption. LBC, while promising, must be balanced against logistical and economic feasibility in public health policy decisions, particularly in resource-constrained settings.

1. World Health Organization. Cervical cancer: Global cancer observatory 2023.
2. Sankaranarayanan R, Nene BM, Shastri SS, Jayant K, Muwonge R, Budukh AM, et al. HPV screening for cervical cancer in rural India. N Engl J Med. 2009;360(14):1385–94. doi:10.1056/NEJMoa0808516.
3. Nayar R, Wilbur DC. The Bethesda System for Reporting Cervical Cytology: A Historical Perspective. Acta Cytol. 2017;61(4–5):359–72. doi:10.1159/000477556.
4. Trosman SJ, Koyfman SA, Ward MC, Al-Khudari S, Nwizu T, Greskovich JF, et al. Effect of human papillomavirus on patterns of distant metastatic failure in oropharyngeal squamous cell carcinoma treated with chemoradiotherapy. JAMA Otolaryngol Head Neck Surg. 2015;141(5):457–62. doi:10.1001/jamaoto.2015.136.
5. Ozkan F, Ramzy I, Mody DR. Glandular lesions of the cervix on thin-layer Pap tests: Validity of cytologic criteria used in identifying significant lesions. Acta Cytol. 2004;48(3):372–9. doi:10.1159/000326387.
6. Arbyn M, Smith SB, Temin S, Sultana F, Castle P. Detecting cervical precancer and reaching underscreened women by using HPV testing on self samples: updated meta-analyses. BMJ. 2018;363:k4823. doi:10.1136/bmj.k4823.
7. Gupta S, Singh P, Asati DP, Gowda SK. An unusual case of scalp ulceration. Indian J Pathol Microbiol. 2024 Jun 4. doi:10.4103/ijpm.ijpm_874_23.
8. Deshpande AH, Kaur A, Sakhuja P. Liquid-based cytology versus conventional cytology: A study of 1000 cases. J Cytol. 2017;34(3):144–8.
9. Vaidya A, Lakhey M, Shrestha S, et al. Comparison of conventional Pap smear and liquid-based cytology in cervical cancer screening. JNMA J Nepal Med Assoc. 2017;56(208):497–501.
10. Rani N, Makkar M, Saluja P, et al. Liquid-based cytology versus conventional cytology in evaluation of cervical smear: A hospital-based study. Int J Reprod Contracept Obstet Gynecol. 2016;5(5):1363–7.
11. Kaur M, Singh P, Satarkar RN, et al. Liquid-based cytology versus conventional cytology in screening of cervical cancer: A hospital-based study. Int J Med Res Rev. 2016;4(12):2117–23.
12. Sharma P, Baheti S, Singh P. Cytomorphological comparison of LBC and conventional Pap smear in screening of cervical cancer. Indian J Pathol Microbiol. 2020;63(4):598–602.
13. Mehrotra R, Singh M, Pandey AN, et al. A comparative study of conventional and liquid-based cytology in cervical cancer screening. J Cytol. 2008;25(2):70–3.
14. Schiffman M, Wacholder S. From India to the world—a better way to prevent cervical cancer. N Engl J Med. 2009;360(14):1453–5. doi:10.1056/NEJMe0901167.
15. Bhatla N, Singhal S. Primary HPV screening and HPV vaccination: How far are we from implementation? Indian J Med Res. 2020;152(5):401–3.