Cervical Cancer Screening: Comparison of Conventional Pap Smear Test, Liquid-Based Cytology, and Human Papillomavirus Testing as Stand-alone or Cotesting Strategies

Abstract

Background: Some countries have implemented stand-alone human papillomavirus (HPV) testing while others consider cotesting for cervical cancer screening. We compared both strategies within a population-based study. Methods: The MARZY cohort study was conducted in Germany. Randomly selected women from population registries aged ≥30 years (n = 5,275) were invited to screening with Pap smear, liquid-based cytology (LBC, ThinPrep), and HPV testing (Hybrid Capture2, HC2). Screen-positive participants [ASC-US+ or high-risk HC2 (hrHC2)] and a random 5% sample of screen-negatives were referred to colposcopy. Post hoc HPV genotyping was conducted by GP5+/6+ PCR-EIA with reverse line blotting. Sensitivity, specificity (adjusted for verification bias), and potential harms, including number of colposcopies needed to detect 1 precancerous lesion (NNC), were calculated. Results: In 2,627 screened women, cytological sensitivities (Pap, LBC: 47%) were lower than HC2 (95%) and PCR (79%) for CIN2+. Cotesting demonstrated higher sensitivities (HC2 cotesting: 99%; PCR cotesting: 84%), but at the cost of lower specificities (92%–95%) compared with HPV stand-alone (HC2: 95%; PCR: 94%) and cytology (97% or 99%). Cotesting versus HPV stand-alone showed equivalent relative sensitivity [HC2: 1.06, 95% confidence interval (CI), 1.00–1.21; PCR: 1.07, 95% CI, 1.00–1.27]. Relative specificity of Pap cotesting with either HPV test was inferior to stand-alone HPV. LBC cotesting demonstrated equivalent specificity (both tests: 0.99, 95% CI, 0.99–1.00). NNC was highest for Pap cotesting. Conclusions: Cotesting offers no benefit in detection over stand-alone HPV testing, resulting in more false positive results and colposcopy referrals. Impact: HPV stand-alone screening offers a better balance of benefits and harms than cotesting. See related commentary by Wentzensen and Clarke, p. 432

Performance of HPV testing, Pap smear and VIA in women attending cervical cancer screening in Kilimanjaro region, Northern Tanzania: a cross-sectional study nested in a cohort

“…Similar findings have been reported in previous studies. [15][16][17] When deciding which test to use for screening, both sensitivity and specificity must be taken into account because tests with low sensitivity will fail in correctly identifying precancerous lesions while tests with low specificity will result in a high proportion of false-positive test results, unnecessary procedures and associated adverse health effects. HPV-test is increasingly recognised as the preferred cervical screening method due to its high sensitivity for detection of CIN2+.…”

[Retracted] Investigation of the Clinical Application Value of HR‐HPV DNA Combined with Liquid Based Cytology in Colposcopy of Cervical Cancer

“…The results of this study showed that the positive rate of liquid-based cytology test results increased with the increase of pathological grade. Liang et al [ 13 ] indicated that some patients with ASCUS detected by liquid-based cytology may be diagnosed with benign lesions or potential malignant changes, which cannot be clearly classified and diagnosed but can only be suggested for the presence of lesions, which is quite different from the gold standard of pathological biopsy under colposcopy. Therefore, cytological test results alone cannot be used as pathological criteria in clinical practice.…”

Colposcopy non-attendance following an abnormal cervical cancer screening result: a prospective population-based cohort study

“…The data stem from randomly recruited participants from the general population (n = 2,627) who were screened within the randomised trial and prospective cohort MARZY study, described previously [ 27 , 28 ]. Briefly, women eligible from the general population (aged 30 to 65 years, with no history of hysterectomy or CC and not pregnant) were screened by office-based gynaecologists at study baseline (R1, 2005–2007) with routine Pap smear, plus an additional MARZY study swab (liquid-based cytology, ThinPrep, Cytyc/Hologic including subsequent HPV testing, Hybrid Capture®2).…”

“…Briefly, women eligible from the general population (aged 30 to 65 years, with no history of hysterectomy or CC and not pregnant) were screened by office-based gynaecologists at study baseline (R1, 2005–2007) with routine Pap smear, plus an additional MARZY study swab (liquid-based cytology, ThinPrep, Cytyc/Hologic including subsequent HPV testing, Hybrid Capture®2). HPV co-testing was investigated [ 27 ]. Participants were administered a questionnaire (Q1) relating to sociodemographic and other factors.…”