European Journal of Cardiovascular Medicine

Cervical cancer remains one of the most prevalent malignancies affecting women worldwide, particularly in low- and middle-income countries, where access to routine screening is limited (1). According to global estimates, cervical cancer is the fourth most common cancer among women, with an estimated 604,000 new cases and 342,000 deaths in 2020 alone (2). Persistent infection with high-risk human papillomavirus (HPV) types is the principal etiological factor in the pathogenesis of cervical neoplasia (3).

Conventional Pap smear cytology has been the cornerstone of cervical cancer screening for decades. However, its limitations, including poor sample adequacy, high false-negative rates, and variable interpretation, have prompted the exploration of alternative techniques (4). Liquid-Based Cytology (LBC), introduced as an improvement over the conventional smear, offers enhanced sample preservation, improved cellular representation, and reduced obscuring artifacts such as blood and inflammation (5). Furthermore, LBC allows for concurrent HPV DNA testing, enhancing its utility in cervical cancer prevention programs (6).

High-risk women—such as those with early onset of sexual activity, multiple sexual partners, smoking habits, and history of sexually transmitted infections—are particularly vulnerable to developing cervical neoplasia and thus require more vigilant screening approaches (7). Early detection of pre-neoplastic and neoplastic cervical lesions through efficient cytological methods like LBC could lead to timely intervention and significantly reduce disease progression and mortality (8).

This study aims to evaluate the utility of Liquid-Based Cytology in the early detection of cervical neoplasia among high-risk women, with histopathological correlation, to determine its diagnostic accuracy and relevance in routine screening protocols.

Study Population
A total of 300 women aged between 21 and 65 years, identified as high-risk for cervical neoplasia, were enrolled based on defined inclusion and exclusion criteria. High-risk status was assigned to women with one or more of the following factors: early onset of sexual activity (before 18 years), multiple sexual partners, history of sexually transmitted infections (STIs), smoking, and immunocompromised conditions such as HIV infection. Written informed consent was obtained from all participants.

Inclusion Criteria

• Sexually active women aged 21–65 years
• Presence of at least one high-risk factor
• Willingness to participate and provide consent

Exclusion Criteria

• Pregnant women
• Women with a known diagnosis of cervical cancer
• History of hysterectomy
• Active vaginal bleeding at the time of examination

Sample Collection and Processing
Cervical samples were collected using a sterile cytobrush after proper visualization of the cervix using a sterile speculum. The collected material was immediately rinsed into a vial containing liquid-based cytology preservative solution (e.g., ThinPrep or SurePath). The samples were then processed in the laboratory following standard LBC protocols to prepare monolayer slides.

Cytological Evaluation
Prepared slides were stained using the Papanicolaou stain and interpreted by experienced cytopathologists using the Bethesda System (2014). Cytological findings were categorized as Negative for Intraepithelial Lesion or Malignancy (NILM), Atypical Squamous Cells of Undetermined Significance (ASC-US), Low-grade Squamous Intraepithelial Lesion (LSIL), High-grade Squamous Intraepithelial Lesion (HSIL), or carcinoma.

Histopathological Correlation
Participants with abnormal cytological findings (ASC-US or higher) underwent colposcopic examination followed by guided cervical biopsy. Histopathological examination was used as the gold standard for confirming the presence of cervical intraepithelial neoplasia (CIN) or malignancy.

Data Analysis
Collected data were entered into Microsoft Excel and analyzed using SPSS software version 26. Descriptive statistics such as frequencies and percentages were used for categorical variables. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of LBC in detecting cervical neoplasia were calculated using histopathological findings as reference.

A total of 300 high-risk women participated in the study. The mean age of the participants was 38.4 ± 8.7 years, with the majority (56.3%) falling in the 31–45 years age group. Sociodemographic and clinical characteristics of the study population are summarized in Table 1.

Out of 300 samples collected, 294 (98%) were deemed satisfactory for evaluation using the Liquid-Based Cytology technique. Cytological analysis based on the Bethesda System (2014) revealed that 228 (77.6%) samples were Negative for Intraepithelial Lesion or Malignancy (NILM), while 66 (22.4%) samples showed cytological abnormalities (Table 2).

Among the abnormal cases, Low-grade Squamous Intraepithelial Lesions (LSIL) were the most frequently observed (30 cases, 10.2%), followed by High-grade Squamous Intraepithelial Lesions (HSIL) in 18 cases (6.1%), Atypical Squamous Cells of Undetermined Significance (ASC-US) in 12 cases (4.1%), and squamous cell carcinoma in 6 cases (2%) (Table 2).

Histopathological confirmation was obtained for all cases with abnormal cytology. Among the 18 HSIL cases, 17 were confirmed as Cervical Intraepithelial Neoplasia Grade II/III (CIN II/III), yielding a confirmation rate of 94.4%. For LSIL, 24 out of 30 cases (80%) were histologically diagnosed as CIN I. ASC-US showed histological changes suggestive of inflammation in 10 out of 12 cases (Table 3).

The diagnostic performance of Liquid-Based Cytology in detecting cervical neoplasia, when compared with histopathological diagnosis as the reference standard, is detailed in Table 4. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of LBC were 91.3%, 95.7%, 89.4%, and 96.5%, respectively.

Table 1: Sociodemographic and Clinical Characteristics of Study Participants (n=300)

Table 2: Distribution of Cytological Findings Based on Bethesda System (n=294)

Table 3: Histopathological Correlation of Abnormal Cytology (n=66)

Table 4: Diagnostic Performance of LBC Compared to Histopathology

The present study highlights the effectiveness of Liquid-Based Cytology (LBC) as a screening tool for early detection of cervical neoplasia among high-risk women. Our findings are consistent with previous literature that supports the improved diagnostic accuracy and sample adequacy of LBC compared to conventional Pap smear techniques (1,2).

In this study, 22.4% of participants had cytological abnormalities, with LSIL being the most common finding. This prevalence is comparable to studies conducted in similar high-risk populations (3,4). The high rate of satisfactory samples (98%) in our study supports the efficiency of LBC in minimizing unsatisfactory or inadequate smears, as also observed by Davey et al. (5).

The diagnostic performance of LBC was notable, with a sensitivity of 91.3% and specificity of 95.7%, aligning with previous reports that document sensitivities ranging from 85% to 95% and specificities above 90% (6,7). This high diagnostic accuracy underscores its potential for widespread adoption in routine cervical screening, particularly in resource-limited settings where missed diagnoses can have significant consequences (8).

Our histopathological correlation showed a strong agreement with cytological findings. HSIL cases had a 94.4% confirmation rate as CIN II/III, demonstrating that LBC is a reliable predictor of high-grade lesions. Similar correlations have been documented in large population-based studies, reinforcing the credibility of cytological interpretation in predicting true pathology (9,10).

Interestingly, 83.3% of ASC-US cases were histologically benign, highlighting the importance of follow-up and colposcopic evaluation in cases with minor cytological abnormalities. The tendency of ASC-US to result in overdiagnosis has been previously discussed in literature, suggesting a need for triage with HPV testing or repeat cytology (11,12).

The prevalence of LSIL and HSIL in our cohort may be attributed to the selected high-risk profile of participants. Risk factors such as early sexual activity, multiple partners, and history of STIs are known to facilitate persistent HPV infection, which in turn increases the risk for cervical neoplastic changes (13). Therefore, targeted screening of high-risk populations using sensitive methods like LBC can significantly enhance early detection and improve outcomes (14).

Despite its advantages, LBC is not devoid of limitations. Cost and the need for specialized processing equipment may hinder its routine implementation in some low-income regions. Nevertheless, the long-term benefits of early detection and prevention of cervical cancer justify the initial investment, as demonstrated in cost-effectiveness models (15).

Liquid-Based Cytology proves to be a reliable and effective screening method for early detection of cervical neoplasia among high-risk women. Its high sensitivity, specificity, and sample adequacy make it a valuable tool in cervical cancer prevention strategies, especially in resource-limited settings.

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