Direct comparison of liquid‐based and conventional cytology in a South African screening trial

Abstract

Our study directly compares the performance of liquid-based (LBC) and conventional cytology for detecting high-grade cervical intraepithelial neoplasia and cancer (CIN 21) in high-risk, previously unscreened women. As part of a larger randomized clinical trial assessing the efficacy and safety of a ''screen and treat'' program for cervical cancer prevention, 5,652 South African women, aged 35 to 65 years, were screened using either ThinPrep or conventional Papanicolaou cytology. The cytology method used (i.e., ThinPrep or conventional) was rotated on a 6-month basis for the duration of the study. Directly following collection of the cytology specimen, all women underwent colposcopy with endocervical curettage and biopsy of all colposcopic abnormalities. Assessment of cytology and histology results was blinded and results were compared using histology-confirmed CIN as the ''gold standard.'' The accuracy of LBC and conventional cytology was statistically equivalent, although the sensitivity of conventional cytology was at least 5 percentage points higher at all cutoff levels. For example, at a cytology cutoff level of low-grade squamous intraepithelial lesion, the sensitivity of LBC was 60.3% for CIN21 vs. 69.1% for conventional cytology and specificity was 94.1% and 94.5%, respectively. LBC specimens were significantly less likely to be ''satisfactory-but-limited-by'' (6.5% vs. 27.9%) but significantly more likely to be unsatisfactory (2.2% vs. 0.8%). Thus, in this high-risk population, the sensitivity of LBC is no greater than the sensitivity of conventional cytology. Because of the higher unit cost of LBC, low resource settings should carefully consider the potential benefits and drawbacks of LBC before adopting this new technology. ' 2005 Wiley-Liss, Inc.Key words: cervical cytology; papanicolaou (Pap) smear; liquidbased cytology; cervical intraepithelial neoplasia Conventional cytology, i.e., the Papanicolaou smear, has been the mainstay of cervical cancer screening since the 1960s and is credited with successfully reducing the incidence and mortality of invasive cervical cancer in many developed countries. 1,2 Nonetheless, the accuracy of this important screening tool remains controversial, with several large meta-analyses suggesting that both the sensitivity and specificity of cervical cytology is relatively low (30% to 87% sensitivity, 86% to 100% specificity). [3][4][5] As an alternative to conventional cytology, liquid based-cytology (LBC) was introduced in the mid-1990s. The purported advantages of LBC include a possible increase in the detection of high-grade cervical intraepithelial neoplasia (CIN 2,3 ), a reduction in the number of unsatisfactory and ''satisfactory-but-limited-by'' specimens, and providing residual cellular material for subsequent molecular testing (e.g., testing for ''high-risk'' types of HPV DNA). On the other hand, the unit cost of LBC methods is substantially more than that of conventional cytology. The substantial increase in unit cost is of particular concern in less-developed...

Evidence-Based Cervical Cancer Screening: The Modern Evolution of the Pap Smear

“…Recent studies have challenged this notion, and to date, the question remains largely unanswered (20,70,71). A systematic review of 56 published studies that included over 1 million slides recently addressed the current literature on this subject (19).…”

A Comparison of Liquid-Based Cytology with Conventional Cytology in Cervical Cancer Screening

“…In addition, the Bethesda system (TBS; 2001), which outlines cytological diagnostic criteria for cervical smears, is only gradually being adopted. It has been reported that the liquid-based cytology (LBC) method is useful for reducing the number of unsatisfactory specimens [1,2,3,4,5,6,7,8,9,10]. Unsatisfactory specimens are ≤1.1%, and one of the most common reasons for unsatisfactory specimens was too few squamous cells [11].…”

“…Unsatisfactory specimens are ≤1.1%, and one of the most common reasons for unsatisfactory specimens was too few squamous cells [11]. In addition, some reports have stated that the LBC method is associated with a higher cancer detection rate than the conventional method [1,8,12,13,14,15], whereas other reports found no difference between both methods [2,3,4,7,9,16,17,18,19,20]. According to meta-analyses and randomized studies, the number of unsatisfactory slides was not lower, or detection of high-grade lesions was not increased compared with conventional cytology [16,17].…”

Age-specific prevalence of cervical human papillomavirus infection and cytological abnormalities in women in Gauteng Province

“…Data from published SA studies suggest important regional differences and an increase in the prevalence of cytological abnormalities when compared with historical data. [3][4][5] Because of the low sensitivity of cytology, it can be assumed that the true prevalence of pre-invasive disease is underestimated by all available data. A single test of cervical cytology, even if optimal, will probably identify fewer than half of all existing pre-invasive cervical disease when measured against the greater yield obtained at colposcopy and directed biopsy.…”