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Reference - BMJ 2016 Oct 4;355:i4924 (level 2 [mid-level] evidence)
- Co-testing with human papillomavirus (HPV) DNA and cervical cytology in routine screening has been shown to increase detection of early cervical cancer and precancerous cervical intraepithelial neoplasia (CIN) lesions for a median of 6.5 years.
- A longer follow-up analysis of the POBASCAM trial in the Netherlands was performed. In the POBASCAM trial, almost 45,000 women were randomized to management based on initial screening with HPV DNA and cytology co-testing vs. cytology testing alone.
- Co-testing led to lower cumulative incidences of cervical cancer and CIN grade 3 or worse (CIN3+) lesions at 9 year and 14 year follow-ups.
- Cumulative incidence rates at 14 years with co-testing were similar to rates at 9 years with cytology testing alone. Also, among women with negative HPV and cytology test results, age ≥ 40 years old was associated with a lower risk of CIN3+ lesions. Together, these results provide indirect evidence that > 5 year screening intervals may be acceptable in women over 40 with negative HPV DNA and cytology results.
Cervical cancer is almost always caused by HPV (Ann Intern Med 2011 Nov 15;155(10):698). For women ≥ 30 years old, American College of Obstetricians and Gynecologists (ACOG) recommends either co-testing with cervical cytology and HPV DNA testing every 5 years (preferred) or cervical cytology every 3 years (acceptable) (Obstet Gynecol 2012 Nov;120(5):1222). Co-testing has been shown to increase detection of early cervical cancer and CIN lesions in women followed for a median of 6.5 years (Lancet 2014 Feb 8;383(9916):524). To assess a longer-term impact of co-testing, a follow-up analysis of the POBASCAM trial in the Netherlands was conducted. In the POBASCAM trial, 44,938 women 29-61 years old were randomized to management based on initial screening with HPV DNA and cytology co-testing vs. cytology testing alone. Subsequent screening was conducted every 5 years with both groups having co-testing at 5 years and cytology alone at 10 years. In this follow-up from the POBASCAM trial, the Netherlands’ nationwide network and registry of histopathology and cytopathology (PALGA) was used for diagnosis of either cervical cancer or CIN3+ lesions, with cumulative incidences reported for assessments at 9 and 14 years after initial screening.
This follow-up analysis included 96% of the randomized women. Co-testing at initial screening led to lower cumulative incidences of cervical cancer and CIN3+ lesions compared to cytology testing alone.
The rate of cervical cancer at 14 years in women with co-testing at initial screening (0.07%) was similar to that at 9 years in women with cytology testing alone (0.09%), as were rates of CIN3+ lesions (0.52% and 0.69%, respectively). Also, in cohort analyses of all women with negative HPV DNA and cytology test results, the cumulative incidence of CIN3+ lesions was 72.1% lower among women ≥ 40 years old than in younger women (p
< 0.001). Incidences of cervical cancer were not significantly different between the age groups.
This study provides important long-term follow-up data, based on a large population-based cohort with a broad age range, showing that co-testing with HPV DNA and cytology in routine screening may decrease the risks of cervical cancer and CIN3+ lesions. However, the utility of co-testing would be more apparent with direct assessments of clinical morbidity and mortality, including for women who had positive HPV DNA or cytology test results on screening. In addition, the cumulative incidence similarities at 14 years with co-testing and 9 years with cytology testing alone, along with a lower risk of CIN3+ lesions in women over 40 years old with negative HPV DNA and cytology test results, provide indirect evidence that >
5 year screening intervals may be acceptable for this population. However, optimally, the effect of different screening intervals would be best evaluated in a randomized trial comparing groups using different screening intervals. Of note, in the Netherlands beginning 2017, screening intervals for HPV negative women over 40 will be extended to 10 years.
For more information, see the Human papillomavirus DNA testing (and related topics on Cervical cancer and Cervical cancer screening) in DynaMed Plus. DynaMed users click here.