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.
New Cervical Cancer Screening Strategies Preferable
In an accompanying editorial, Dr. Guglielmo Ronco and his colleagues said that 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. Ronco and his colleagues wrote (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, noted Dr. Ronco of the Centre of Cancer Prevention in Turin, Italy, and his associates.
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 and his coauthors said they had no relevant financial disclosures.
The study was funded by Roche Molecular Systems. Dr. Castle said he has a nondisclosure agreement to work with Roche on the analysis of their clinical trial but receives no financial compensation. Other authors on the study disclosed that they are employed by Roche Molecular Systems and/or have stock or stock options in the company, or that they have received consulting fees, honoraria, and/or other compensation from Roche, BD Diagnostics, Qiagen, Gen-Probe, Ventana, and/or Merck.