More Evidence of HPV Link to Cervical Cancer

Young women who developed cervical neoplasia after normal baseline cervical cytology were more than nine times as likely to test positive for high-risk human papillomavirus (HPV) infection as compared with women who did not develop cervical pathology, according to a retrospective study of 9,000 women.

For women younger than 30, infection with HPV16/18 had the strongest association with high-grade cervical neoplasia (CIN2+). Among women ≥30, infection with any HPV strain increased the risk of CIN2+.

Across the age range from 23 to 59, HPV infection increased the risk of high-grade CIN or cervical cancer by two to 20 times (not all statistically significant), as compared with women who did not develop high-grade CIN, Karen Belkic, MD, PhD, of the Karolinska Institute in Stockholm, and coauthors reported in Cancer.

“When we view our results together with the results of other such studies, we conclude that the finding of HPV among women with NILM (cytology negative for intraepithelial lesions or malignancy) findings at baseline are associated with a significantly elevated future risk of high-grade CIN,” the authors concluded. “The accumulated evidence indicates that a positive HPV finding is the strongest risk indicator for future CIN among women 30 years old or older. On the other hand, HPV was detected in a substantial percentage of the control group younger than 30 years with baseline NILM findings.”

“Evidence-based guidelines would be further enhanced by studies with systematically repeated HPV measures,” they added. “In this way, transient positive HPV findings, with a minimal future risk of high-grade CIN, could be more confidently identified. This would be especially helpful for preventing the harms of overscreening and overtreatment, particularly among younger women.”

The study evaluated a previously unanswered question about HPV testing and cervical cancer: Does a single positive HPV test put a woman at higher risk for cervical cancer throughout her lifetime?

“That’s an important issue as we move into an era of primary HPV screening,” said Jennifer Young Pierce, MD, of the University of South Alabama in Mobile. “It was important to prove that, even without the Pap diagnosis, the HPV test alone could indicate increased risk.”

The Swedish study and others like it can help inform screening and treatment decisions in the U.S., which does not have national health databases that permit longitudinal studies of issues, said Pierce, who is a clinical expert for the Society of Gynecologic Oncology. The data might help set the stage for clinical trials, such as an evaluation of treatment for patients who test positive for HPV as a means to prevent cancer.

To determine the impact of baseline HPV status on subsequent risk of CIN2+, Belkic and colleagues performed a nested case-control study involving women enrolled in the Swedish National Cervical Screening Registry during 2005-2007. Investigators identified 8,817 women who had benign cervical cytology results and no history of CIN2+.

During follow-up through 2014, 96 women with NILM at baseline developed CIN2+. Each of the 96 patients was matched with five women from the registry who had NILM and did not develop CIN2+. Cervical specimens obtained at enrollment were retrospectively tested for HPV in 2016.

HPV results were positive for 51% of cervical specimens from the CIN2+ group and 45.8% tested negative. That compared with 14.0% and 83.8% positive and negative results, respectively, in the control group (P<0.001). Almost a third (31.3%) of the CIN2+ group tested positive for the high-risk HPV16/18 vs 6.3% of the control group (P<0.001). Analysis of the HPV test results by age groups (5-year intervals) consistently showed higher rates of any HPV infection and HPV16/18 infection in the cases vs control group.

Among women 23-59 in the CIN2+ group, the odds ratio for detection of any HPV infection was 6.78 vs the control group, increasing to OR 8.93 for HPV16/18. In the <30 age group, the odds ratio for detecting HPV16/18 was 9.44 vs the control group and 4.95 for detection of any HPV strain. Among women ≥30, the odds for detection of HPV16/18 or any HPV strain were 8.16 and 8.01, respectively.

“Age-stratified results were most informative because for women younger than 30 years, HPV16/18 was significantly associated with the future risk of CIN2+,” the authors noted in their discussion. “This significant association was not found for the other HPV subtypes alone among these younger women. Moreover, baseline HPV was detected in the control group in a significantly larger percentage of the women younger than 30 in comparison with those 30 years old or older.”