A longitudinal cohort study published by Gottschlich et al in Cancer Epidemiology, Biomarkers & Prevention investigated the optimal interval between screening tests and the long-term risk of cervical precancer or worse (CIN2+). Researchers found that the risk of cervical precancer 8 years after a negative human papillomavirus (HPV) screening result was comparable to the risk at 3 years after a negative standard cytology screening, the current benchmark for acceptable risk. The findings suggest that primary screening intervals for HPV detection may safely be extended beyond the current 5-year recommendation, potentially reducing barriers to screening.
Cervical cancer is the fourth most common cancer in women worldwide, accounting for about 660,000 new cases each year and nearly 350,000 deaths globally—and about 14,000 new cases and over 4,000 deaths each year in the United States. Despite these dire statistics, effective primary prevention strategies, including HPV vaccination, and secondary prevention strategies, such as cervical cancer screening, make cervical cancer a highly preventable disease. As a result, the World Health Organization has called for the global elimination of cervical cancer—defined as reducing new cases to 4 or fewer per 100,000 annually—by 2030. However, critical questions remain about how best to implement primary HPV screening.
Study Methodology
The researchers examined data from women and individuals with a cervix who had received one or two negative HPV screening(s) (HPV1 cohort, n = 5,546; HPV2 cohort, n = 6,624) during a randomized trial and women and individuals with a cervix with one or two normal cytology results (BCS1 cohort, n = 782,297; and BCS2 cohort, n = 673,778) extracted from the provincial screening registry.
The data were derived from the Human Papillomavirus FOr CervicAL Cancer Prevention (HPV FOCAL) randomized clinical trial from January 2008 through December 2016, and its 14-year longitudinal follow-up, the FOCAL-DECADE study, for the HPV screening cohorts. Data were used from the British Columbia Cervix Screening Program during the same interval for the cytology cohorts. Participants from each cohort were between the ages of 25 and 65 years at their initial screen.
All of the participants were followed through the registry for 14 years. The long-term risk of cervical precancer or worse (CIN2+) was compared between the HPV and cytology cohorts.
Results
The cumulative risk of cervical intraepithelial neoplasia grades 2 (CIN2), 3 (CIN3), and higher (referred to as CIN2+ or CIN3+) were calculated for each cohort. The risk of CIN2+ 8 years after one (3.2/1,000) or two (2.7/1,000) negative HPV test(s) was similar to that of 3 years after one (3.3/1,000) or two (2.5/1,000) negative cytology screen(s). After 6 years—longer than the current 5-year guidelines—HPV screens showed lower risk after both one (2.5/1,000) and two (2.3/1,000) negative tests. Risk of CIN3+ was also lower or similar in the HPV cohorts following 8 years compared to the cytology cohorts after 3 years.
While the risk for CIN2+ was higher for HPV screening at intervals longer than 8 years compared to cytology after 3 years, the detection of cervical precancer still remained low after negative HPV screening during the 14-year duration of the study period, and was significantly lower than normal cytology screening over that period.
“Risk of CIN2+ 8 years after screen in HPV cohorts was comparable to risk after 3 years in cytology cohorts (the benchmark for acceptable risk),” concluded the study authors.
Future studies will continue to follow these cohorts to better understand optimal implementation strategies for HPV screening, including appropriate ages for entry and exit into screening and triage management strategies.
Clinical Significance
“HPV screening performs better than cytology by detecting more precancer earlier, which can then be treated earlier,” said lead study author Anna Gottschlich, PhD, MPH, Assistant Professor at Wayne State School of Medicine and the Barbara Ann Karmanos Cancer Institute, in a statement. “We saw that in our study population, even those who had only one negative HPV test were at very low risk for the development of cervical precancer for many years after the negative test.
“Policy leaders need to consider a broad array of factors in health decision-making in their settings when considering how to prioritize HPV-based screening over cytology. Optimal implementation strategies depend on the kind of screening engagement and resources available in each specific program. Extending intervals require health system considerations to ensure adequate continued engagement to minimize loss to follow-up,” she concluded.
Disclosure: Funding for this study was provided by the National Institutes of Health, the Canadian Institutes for Health Research, and the Michael Smith Foundation for Health Research. For full disclosures of the study authors, visit aacrjournals.org/cebp.
