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The risk of developing cervical neoplasia 8 years after human papillomavirus (HPV) testing was similar to 3 years after a negative Pap test, a large longitudinal cohort study showed.
Patients with one or two negative HPV tests had risks of grade 2 or higher cervical intraepithelial neoplasia (CIN2+) of 3.2 and 2.7 per 1,000, respectively, at 8 years, similar to the rates of 3.3 and 2.5 per 1,000 at 3 years after one or two negative Pap tests. The risk of CIN2+ 6 years after one or two negative HPV tests was lower compared with the current guideline-recommended interval of 5 years.
The risk of CIN3+ was also lower 8 years after HPV testing as compared with 3 years after negative cytology, reported Anna Gottschlich, PhD, of Wayne State University and the Karmanos Cancer Institute in Detroit, and colleagues in .
Detection of cervical cancer precursor lesions remained low over 14 years after negative HPV screening, significantly lower compared with cytology screening.
"HPV screening performs better than cytology by detecting more precancer earlier, which can then be treated earlier," Gottschlich said in the American Association for Cancer Research. "We saw that in our population, even those who had only one negative HPV screen 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," she added. "Optimal implementation strategies depend on the kind of screening engagement and resources available in each specific program."
Adoption of HPV screening as the standard for clinical practice still faces obstacles in terms of reimbursement and overcoming the long history of Pap testing, said Robert Edwards, MD, of the UPMC Hillman Cancer Center in Pittsburgh.
"If HPV screening was the national standard and always reimbursed (national healthcare like in Europe), we could extend the screening interval but because there is nationwide heterogeneity in practice and reimbursement for cytology versus HPV screening, we cannot extend screening intervals for all," he told app via email. "Also the Pap smear remains a constant in some patients' minds to be looked at by a pathologist. Some in the community refuse to accept prolonged screening intervals."
A transition from cervical cytology to HPV-based screening for cervical cancer has evolved over the past two decades. As a result of the availability of high-performance HPV screening technology and the HPV vaccine, cervical cancer has become highly preventable, Gottschlich and colleagues noted in their introduction to the study.
The U.S. Preventive Services Task Force recommends three options for cervical cancer screening: cervical cytology every 3 years, HPV screening every 5 years, or co-testing every 5 years. Many high-income nations have established cytology-based screening programs that have led to a decreased incidence of cervical cancer. However, some nations still have rates that exceed the World Health Organization recommendations for disease elimination (≤4 per 100,000 annually), including the U.S., which has an annual incidence of 7.6 per 100,000, the authors continued.
The optimal interval for HPV screening has yet to be determined, which provided a rationale for the current study. The investigators compared the long-term risk of cervical precancer after negative HPV screening versus negative cytology, which has informed screening recommendations.
Gottschlich and colleagues used data from the Canadian conducted from January 2008 through December 2016, as well as a 14-year longitudinal follow-up study for the HPV screening cohorts. Their analyses involved four cohorts: 5,546 women who had one negative HPV test; 6,624 who had two consecutive negative HPV screens 4 years apart; 782,297 women who had one negative screening cytology; and 673,778 women who had two consecutive negative cytology screens 2-3 years apart.
The primary outcome was cumulative risk of CIN2+ and CIN3+ precursor lesions in the HPV-screened and cytology-screened cohorts. The investigators also compared hazard ratios associated with a single negative HPV screen and two consecutive negative screens 4 years apart.
The overall results showed that rates of CIN2+ and CIN3+ lesions were lower after one or two HPV screening tests as compared with cytologic screening. The incidence of CIN2+ and CIN3+ was lower across all age groups with HPV screening versus cytology. The cumulative risk of CIN2+ and CIN3+ remained lower over the follow-up period in patients screened with HPV testing.
At 10 years, the cumulative risk of CIN2+ in the patients screened by HPV testing was 4.7 and 3.9 per 1,000 after one and two negative HPV tests, respectively, versus 14.8 and 14.1 per 1,000 after negative cytology tests. A similar difference existed for CIN3+ -- 2.1 and 3.0 per 1,000 with HPV testing versus 9.9 and 9.6 per 1,000 with cytology.
Disclosures
The study was supported by the NIH, Canadian Institutes for Health Research, and the Michael Smith Foundation for Health Research.
Gottschlich reported no relevant financial relationships with industry.
Edwards disclosed a relationship with Merck.
Primary Source
Cancer Epidemiology, Biomarkers & Prevention
Gottschlich A, et al "Evidence of decreased long-term risk of cervical precancer after negative primary HPV screens compared to negative cytology screens in a longitudinal cohort study" Cancer Epidemiol Biomarkers Prev 2024; DOI: 10.1158/1058-9965.EPI-23-1587.