Expert Commentary

Q Is HPV testing alone a reliable cervical cancer screen?

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A Not at this time, although more women 35 to 60 years of age with cervical intraepithelial neoplasia 2 or higher (CIN2+) harbor DNA evidence of the human papillomavirus (HPV) than manifest cytologic changes of neoplastic transformation. That is, HPV-positive results are more common than abnormal cytology in screening. Thus, the authors present an alternative strategy of beginning screening with hybrid capture 2 (HC2) testing for HPV in women aged 35 and above, with cytologic analysis of HC2-positive cases second and colposcopy for those who test positive (atypical squamous cell changes or higher-grade abnormalities) in both. They fall short of recommending this tactic for clinical practice.

Strengths of the study include large population

In this massive multicenter trial involving more than 33,000 women, participants were randomly assigned to screening with conventional cytology or to the experimental arm. This was a high-risk population 35 to 60 years of age, of which just slightly over 50% had undergone cervical screening within 4 years. In the first phase of the trial, which is the focus of this study, women in the experimental arm underwent screening with liquid-based cytology and HPV testing, and in the second phase, women were screened using HPV testing alone. The key endpoint for comparison: histology-confirmed CIN2+ after an abnormal screening test. Abnormal screening was defined as cytologic results of atypical squamous cells of undetermined significance or higher (ASCUS+) in the conventional cytology group, and ASCUS+ or a positive HC2 test in the experimental arm.

Because of the large sample size, it was deemed impossible to perform the “gold standard” diagnostic test (colposcopy and biopsy) in women with negative screening, so true sensitivity, specificity, and negative predictive value of the testing strategies could not be determined (TABLE). Because of this, the authors labeled and compared detection rates of CIN2+ in the 2 screening groups as “relative sensitivity.”


How to “screen” a screening test

The ideal screening test focuses on disease that is prevalent. To determine the value of the test, all patients undergo definitive evaluation—in the case of cervical cancer screening, this would entail colposcopy and biopsy—to determine the actual disease rate and the “disease-free” rate.
Positivea (true positive)b (false positive)
Negativec (false negative)d (true negative)
A test’s sensitivity is defined as a/a+c, specificity as d/b+d, positive predictive value as a/a+b, and negative predictive value as d/c+d.
If the entire screening population is not screened with the “gold-standard” reference test, the values of “c” and “d” cannot be determined. In the study by Ronco and colleagues, the only true rate that can be calculated is positive predictive value.

Expert Commentary

This study leads to several key conclusions:

Practice recommendations

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