“However, until clinicians become comfortable with the use of HPV as a first-line test, they might initially favor co-testing, and so co-testing could have an underlying merit that is difficult to quantify,” Dr. Castle and his associates wrote.
In addition, “the decision to switch from co-testing to HPV testing alone, and the intervals between screenings, will ultimately depend on clinicians' perceptions of acceptable risks,” they said.
“Nevertheless, on the basis of our findings, we suggest that detection of HPV-16, HPV-18, or both combined with a raised threshold of abnormal cervical cytology (LSIL or worse) might be preferable to the existing recommendations for management of HPV-positive women,” according to the investigators.
They noted that testing and genotyping for HPV-16, HPV-18, or both – with or without liquid-based cytology – can provide potentially cost-effective and safe cervical cancer screening.
“Because the HPV-16 and HPV-18 readouts for the cobas HPV test are provided concurrently with the pooled detection of other carcinogenic HPV genotypes,” the use of this test to triage HPV-positive women for colposcopy could prove much more efficient than cytology, they added.
Also, a strategy of applying cytology reflexively to those who are HPV positive without HPV-16 or HPV-18 genotype, with referral to colposcopy only if they have LSIL or HSIL, or worse, would increase the sensitivity for detection of CIN 3 or worse in HPV-positive women to a level above that provided by HPV-16 and HPV-18, or both, without sacrificing good PPV, they said. The comparative performance and cost-effectiveness of various strategies will need to be assessed in future studies to identify best practices, they noted.
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Standalone HPV Testing as Primary Cervical Cancer Screening?
A cervical cancer screening strategy that allows immediate identification of all women with lesions needing treatment would be preferable to the current approach of rescreening HPV-positive women with normal cytology at 1 year, with colposcopy performed if infection is still present or if cytology has become abnormal.
“Unfortunately, all combinations of genotyping and cytology in Castle and colleagues' study had less than 80% sensitivity, leading the investigators to recommend test repetitions after 1 year,” Dr. Guglielmo Ronco and his colleagues wrote in an accompanying editorial (Lancet Oncol. 2011;12:831-2).
Still, the increased sensitivity provided by the combined triage tests would allow some CIN 3 or worse lesions to be detected earlier, they noted.
Furthermore, strategies using other biomarkers to triage HPV-positive women are currently being assessed; the cross-sectional sensitivity of immunochemistry for p16INK4a overexpression for CIN 3 or worse, for example, is 91%, which suggests that short-term retesting could be avoided in those who test negative for p16INK4a. Dr. Ronco and his colleagues warned, however, that since HPV-positive women are at increased risk for developing new lesions, premature reallocation to screening intervals as long as those recommended for HPV-negative women “might not be advisable.”
“Additional longitudinal data are needed to define the safest time interval before retesting in women with HPV infection who were negative for p16INK4a or any other triage test,” they wrote.
They also noted that the findings of this study, though designed for developed countries, can provide useful information about triage strategies for “countries where high-quality cytology has been difficult to implement and combinations of HPV tests might eventually offer a more sustainable option.”
DR. RONCO is with the Centre of Cancer Prevention in Turin, Italy. He and his coauthors said they had no relevant financial disclosures.