HPV−cytology cotesting every 3 years lowers population rates of cervical precancer and cancer
Silver MI, Schiffman M, Fetterman B, et al. The population impact of human papillomavirus/cytology cervical cotesting at 3-year intervals: reduced cervical cancer risk and decreased yield of precancer per screen. Cancer. 2016;122(23):3682−3686.
Current guidelines on screening for cervical cancer in women 30 to 65 years of age advise the preferred strategy of using cytology alone every 3 years or combining HPV testing and cytology every 5 years.1 These guidelines, based on data available at the time they were written, were meant to offer a reasonable balance between timely detection of abnormalities and avoidance of potential harms from screening too frequently. However, many patients are reluctant to postpone repeat testing to the extent recommended. Several authorities have in fact asked that screening intervals be revisited, perhaps allowing for a range of strategies, contending that the level of protection once provided by annual screening should be the benchmark by which evolving strategies are judged.2 Today, they point out, the risk of cancer doubles in the 3 years following an initial negative cytology result, and it also increases by lengthening the cotesting interval from 3 to 5 years. They additionally question the validity of using frequency of colposcopies as a surrogate to measure harms of screening, and suggest that many women would willingly accept the procedure's minimal discomfort and inconvenience to gain peace of mind.
The study by Silver and colleagues gives credence to considering a shorter cotesting interval. Since 2003, Kaiser Permanente Northern California (KPNC) has implemented 3-year cotesting. To determine actual clinical outcomes of cotesting at this interval, KPNC analyzed data on more than 1 million women in its care between 2003 and 2012. Although investigators expected that they might see decreasing efficiency in cotesting over time, they instead found an increased detection rate of precancerous lesions per woman screened in the larger of 2 study cohorts.
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Details of the study
Included were all women 30 years of age or older enrolled in this study at KPNC between 2003 and 2012 who underwent HPV−cytology cotesting every 3 years. The population in its entirety (1,065,273 women) was deemed the "open cohort" and represented KPNC's total annual experience. A subset of this population, the "closed cohort," was designed to gauge the effect of repeated screening on a fixed population and comprised only those women enrolled and initially screened between 2003 and 2004 and then followed longitudinally until 2012.
For each cohort, investigators calculated the ratios of precancer and cancer diagnoses to the total number of cotests performed on the cohort's population. The 3-year testing periods were 2004−2006, 2007−2009, and 2010−2012. Also calculated in these periods were the ratios of colposcopic biopsies to cotests and the rates of precancer diagnoses (TABLE).
In the open cohort, the biopsy rate nearly doubled over the course of the study. Precancer diagnoses per number of cotests rose by 71.5% between the first and second testing periods (P = .001) and then eased off by 10% in the third period (P<.001). These corresponding increases throughout the study yielded a stable number of biopsies (16 to 22) needed to detect precancer.
In the closed long-term cohort, the biopsy rate rose, but not as much as in the open cohort. Precancer diagnoses per number of cotests rose by 47% between the first and second periods (P≤.001), but in the third period fell back by 28% (P<.001) to a level just above the first period results. The number of biopsies needed to detect a precancerous lesion in the closed cohort rose from 19 to 33 over the course of the study, suggesting there may have been some loss of screening efficiency in the fixed group.
Patients are dissatisfied with the 5-year screening interval for cotesting, and many of them wish to return to shorter interval testing. What this large-scale study shows is that 3-year cotesting safely lowers population rates of cervical precancer and cancer and does so at an interval that should help ease patients' minds.
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