Reply to comparison of cervical cancer screening results among 256,648 women in multiple clinical practices
Blatt et al have presented data regarding the correlations of routine high-risk human papillomavirus (HPV) and Papanicolaou (Pap) “cotesting” results with biopsy diagnosis in approximately one-quarter of million women aged 30 to 65 years. These data complement those from Kaiser Permanente Northern California, in which >1 million women aged 30 to 65 years have been cotested since 2003. Unfortunately, the analysis by Blatt et al introduces a bias that favors disease detected by Pap testing and, by extension, cotesting. Guidelines recommend that women who have an HPV-positive atypical squamous cells of undetermined significance, low-grade squamous intraepithelial lesion, or more severe cytologic interpretation are referred for immediate colposcopy. Women who test positive for HPV but have a negative Pap test (HPV1/ Pap2) are recommended to undergo rescreening within a year and sent to colposcopy if they have a cytologic abnormality or evidence of persistent high-risk HPV. Thus, including only those women who underwent a biopsy within 1 year excludes a significant percentage of women with HPV1/Pap2 results who came back for rescreening, because many women do not come back exactly at 1 year (or less) but return over the course of several months past the one-year anniversary. Restricting to 1-year follow-up likely results in an underattribution of disease detected by HPV screening and missed by Pap testing. It therefore will be important to reanalyze these data with ample follow-up of the women with HPV1/ Pap2 results to better reflect the real-world performance of HPV testing and cotesting. More importantly, the critical question should be what cervical cancer screening strategy is more effective and cost-effective, and has a better benefits-to-harms ratio over a “screening lifetime.” Although a single cotest will always be more sensitive than either test alone, how does cotesting every 5 years compare with HPV testing alone every 3 or 4 years projected over 20 or 30 years? For example, over a 20-year period, are 4 rounds of cotesting every 5 years more effective than 5 rounds of HPV testing alone every 4 years? Recent data from Kaiser Permanente Northern California have demonstrated that the 5-year reassurance after a negative cotest is approximately the same as the 4-year reassurance after a negative HPV test. Cotesting every 5 years would have one fewer HPV test but 4 more Pap tests than HPV testing every 4 years to achieve approximately the same level of effectiveness in that period of time. Over a 30-year period, cotesting every 5 years would have 4 fewer HPV tests but 6 more Pap tests and possibly less reassurance than HPV testing every 3 years. Thus, screening modalities must be projected over the screening lifetime to estimate its relative programmatic benefits, harms, and costs to make an informed decision regarding which approach is best for women.