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Evidence summaries

Human Papillomavirus Testing Versus Conventional Cytology for Cytological Cervical Lesions

Human papillomavirus tests (HPV tests) are effective and more sensitive for finding cytological cervical lesions than conventional cytology but are less specific. However, a negative HPV test is more reassuring than a negative cytological test. Level of evidence: "A"

A Cochrane review 2 [Abstract] included 40 studies with more than 140 000 women aged between 20 and 70 years old participating in a cervical cancer screening programme without previous cytological abnormalities. For CIN 2+, pooled sensitivity estimates for hybrid capture 2 (HC2; 1 pg/mL threshold), conventional cytology (CC) and liquid-based cytology (LBC) (ASCUS+) were 89.9%, 62.5% and 72.9%, respectively, and pooled specificity estimates were 89.9%, 96.6%, and 90.3%, respectively. The results did not differ by age of women (less than or greater than 30 years old), or in studies with verification bias. Accuracy of HC2 was, however, greater in European countries compared to other countries. The results for the sensitivity of the tests were heterogeneous ranging from 52% to 94% for LBC, and 61% to 100% for HC2. Overall, the quality of the evidence for the sensitivity of the tests was moderate, and high for the specificity.The relative sensitivity of HC2 versus CC for CIN 2+ was 1.52 (95% CI: 1.24 to 1.86) and the relative specificity 0.94 (95% CI: 0.92 to 0.96), and versus LBC for CIN 2+ was 1.18 (95% CI: 1.10 to 1.26) and the relative specificity 0.96 (95% CI: 0.95 to 0.97). The relative sensitivity of HC2 versus CC for CIN 3+ was 1.46 (95% CI: 1.12 to 1.91) and the relative specificity 0.95 (95% CI: 0.93 to 0.97). The relative sensitivity of HC2 versus LBC for CIN 3+ was 1.17 (95% CI: 1.07 to 1.28) and the relative specificity 0.96 (95% CI: 0.95 to 0.97).

For every 1000 women screened, around 20 women will have precancerous changes. Of these 16 will be correctly identified with the HPV vs 12 with the Pap test (4 vs 8 will be missed, respectively). For every 1000 women screened, 980 women will not have precancerous changes. The HPV test will correctly identify 879 of these women vs 951 women with the Pap test (but 101 vs 29 women will be incorrectly told that they have a lesion, respectively).

Another Cochrane review 1 [Abstract] included 43 studies with a total of 13 196 women with atypical squamous cells of undetermined significance (ASCUS) (5 261 of them also had a repeat Pap smear) and 9 983 women with low-grade squamous intra-epithelial lesions (LSIL) (1 591 of them also had a repeat Pap smear). The aim was to compare the accuracy of DNA testing of high-risk types of the human papillomavirus (hrHPV) with the Hybrid Capture 2 (HC2) assay against that of repeat cytology for detection of underlying cervical intraepithelial neoplasia of grade 2 or worse (CIN2+) or grade 3 or worse (CIN3+) in women with ASCUS and LSIL. The pooled sensitivity of HC2 was significantly higher than that of repeat cytology at cut-off ASCUS+ to detect CIN2+ in both triage of ASCUS and LSIL: relative sensitivity of 1.27 ( 95% CI 1.16 to 1.39; P value < 0.0001) and 1.23 (95% CI 1.06 to 1.4; P value 0.007), respectively. In ASCUS triage, the pooled specificity of the triage methods did not differ significantly from each other (relative specificity: 0.99 ,95% CI 0.97 to 1.03; P value 0.98). However, the specificity of HC2 was substantially, and significantly, lower than that of repeat cytology in the triage of LSIL (relative specificity: 0.66 , 95% CI 0.58 to 0.75, P value < 0.0001).

References

  • Arbyn M, Roelens J, Simoens C et al. Human papillomavirus testing versus repeat cytology for triage of minor cytological cervical lesions. Cochrane Database Syst Rev 2013;(3):CD008054. [PubMed]
  • Koliopoulos G, Nyaga VN, Santesso N et al. Cytology versus HPV testing for cervical cancer screening in the general population. Cochrane Database Syst Rev 2017;8():CD008587. [PubMed]

Primary/Secondary Keywords