Article

Human Papillomavirus Testing and Liquid-Based Cytology: Results at Recruitment From the New Technologies for Cervical Cancer Randomized Controlled Trial

Unit of Cancer Epidemiology, Centro per la Prevenzione Oncologica Piemonte, 10123 Turin, Italy.
Journal of the National Cancer Institute (Impact Factor: 12.58). 06/2006; 98(11):765-74. DOI: 10.1093/jnci/djj209
Source: PubMed

ABSTRACT

Although testing for human papillomavirus (HPV) has higher sensitivity and lower specificity than cytology alone for detecting cervical intraepithelial neoplasia (CIN), studies comparing conventional and liquid-based cytology have had conflicting results.
In the first phase of a two-phase multicenter randomized controlled trial, women aged 35-60 years in the conventional arm (n = 16,658) were screened using conventional cytology, and women in the experimental arm (n = 16,706) had liquid-based cytology and were tested for high-risk HPV types using the Hybrid Capture 2 assay. Women in the conventional arm were referred to colposcopy with atypical cells of undetermined significance (ASCUS) or higher and those in the experimental arm were referred with ASCUS or higher cytology or with a positive (> or = 1 pg/mL) HPV test. Sensitivity and positive predictive value (PPV) for detection of cervical intraepithelial neoplasia grade 2 or higher (CIN2+) were calculated.
The screening methods and referral criterion applied in the experimental arm had higher sensitivity than that in the conventional arm (relative sensitivity = 1.47; 95% confidence interval [CI] = 1.03 to 2.09) but a lower PPV (relative PPV = 0.40; 95% CI = 0.23 to 0.66). With HPV testing alone at > or = 1 pg/mL and at > or = 2 pg/mL, the gain in sensitivity compared with the conventional arm remained similar (relative sensitivity = 1.43, 95% CI = 1.00 to 2.04 and relative sensitivity = 1.41, 95% CI = 0.98 to 2.01, respectively) but PPV progressively improved (relative PPV = 0.58, 95% CI = 0.33 to 0.98 and relative PPV = 0.75, 95% CI = 0.45 and 1.27, respectively). Referral based on liquid-based cytology alone did not increase sensitivity compared with conventional cytology (relative sensitivity = 1.06; 95% CI = 0.72 to 1.55) but reduced PPV (relative PPV = 0.57; 95% CI = 0.39 to 0.82).
HPV testing alone was more sensitive than conventional cytology among women 35-60 years old. Adding liquid-based cytology improved sensitivity only marginally but increased false-positives. HPV testing using Hybrid Capture 2 with a 2 pg/mL cutoff may be more appropriate than a 1 pg/mL cutoff for primary cervical cancer screening.

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    • "The biopsy rate was doubled (rate ratio 2.24; 95%CI: 2.09– 2.39) in the NTCC trial, where all HPV-positive women were directly referred for colposcopy, while it was not increased in studies using cytological triage (POBASCAM, Swedescreen, ARTISTIC) [141] (level of evidence: I). Co-testing of all women with both HPV and cytology compared with primary HPV testing alone led to increased unnecessary colposcopy [142,143] (level of evidence: I). As the efficacy results were similar, the data support the use of the least extensive strategy (primary HPV screening with triaging by cytology before referral) (level of evidence I). "
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    • "In the current study, the HPV E6/E7 mRNA test was negative in 28.1% of histologically confirmed ≥Grade 2 cervical intraepithelial neoplasia cases. It is assumed that some ≥Grade 2 cervical intraepithelial neoplasia cases may clear their infections or cell abnormalities spontaneously restraining E6/E7 mRNA expression (Ronco et al., 2006Ronco et al., , 2007 Confortini et al., 2010), but they require time to recover completely. It is therefore possible that ≥Grade 2 cervical intraepithelial neoplasia cases with negative E6/E7 transcripts could be more likely to regress or less likely to progress toward cancer, as HPV infection could have been cleared or viral gene expression is very low. "
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