Laboratorians may see a rise in the volume of human papillomavirus (HPV) tests to screen for cervical cancer. In revised guidelines, the United States Preventive Services Task Force (USPSTF) for the first time is recommending standalone high-risk (hrHPV) testing as one of several options for women ages 30 to 65 years.  The task force in 2012 broke new ground by offering a cotesting option with Pap and HPV every 5 years for women in this age group. The 2018 update went a step further, proposing multiple options that include hrHPV every 5 years as well as two previous recommendations: Pap every 3 years or cotesting every 5 years. All of these options are similarly effective in detecting cervical cancer, according to task force member Carol Mangione, MD, MSPH.

Younger women should continue to get tested with Pap every 3 years. “We determined that the benefits of continuing Pap smears every three years for women ages 21-29 were greater than for switching to HPV testing alone because most HPV infections in this age group will resolve spontaneously,” Mangione explained to CLN Stat.  For some women, the Pap will continue to be the preferable screening option, depending on individual circumstances. “Women should discuss with their doctor which testing strategy is best for them,” she said.

The task force published its recommendations in the Journal of the American Medical Association (JAMA) following an extensive review of clinical and cohort studies that compared various screening combinations for cytology and hrHPV, and a decision analysis that evaluated screening intervals, harms and benefits of different screening methods, and optimal ages and intervals for screening.

Investigators defined benefit as the years of life gained from cervical cancer prevention, whereas harm was defined as the number of invasive tests and procedures performed, Lee A. Learman, MD, PhD, professor of obstetrics and gynecology at Florida Atlantic University’s Schmidt College of Medicine, and author of a related editorial on the USPSTF’s recommendations, told CLN Stat.

Four studies identified in the review found that primary hrHPV testing detected higher rates of stage 3 (or worse) cervical intraepithelial neoplasia compared with the standalone Pap test in the first round of testing. In comparing the Pap, hrHPV and cotesting methods, the latter two methods were associated with higher colposcopy and false-positive rates, “which could lead to more treatments with potential harms,” authors of the review cautioned.

Overall, the clinical literature suggests that hrHPV is a more sensitive test than Pap testing in identifying both stage 2 and 3 cancers, the task force indicated in its recommendation statement. “The USPSTF concludes with high certainty that the benefits of screening every 3 years with cytology alone, every 5 years with hrHPV testing alone, or every 5 years with both tests (cotesting) in women aged 30 to 65 years outweigh the harms,” the task force concluded in its recommendations statement. The anticipation is hrHPV testing every 5 years for women in the 30 to 65 age cohort could reduce cervical cancer mortality from 8.34 to 0.29 deaths per 1,000 women.

In other recommendations, the task force discouraged screening in women older than age 65 with a previous history of screening, in women younger than 21, and in women without a cervix, due to evidence suggesting that it would offer little to no benefit.

USPSTF’s latest recommendations represent the growing credibility of HPV testing as a screening tool for cervical cancer. Various studies   have reported on the test’s superiority to Pap testing as a more sensitive and less expensive alternative. Most recently, a study published in the JAMA found that HPV testing was more efficient than Pap testing in identifying precancers.

The 2018 guidelines “continue the trend of decreasing participant burden by lengthening screening intervals, making the ‘annual Pap’ a historical artifact,” Learman and Francisco A. R. Garcia, MD, MPH, wrote in the related editorial.

HPV testing every 5 years is an attractive option for patients who want to avoid pelvic exams and Pap smears, Learman told CLN Stat. That said, it will take a long while before HPV testing replaces cervical cytology, if ever. “The Pap test is well-known and accepted by patients and women’s healthcare providers, and there would need to be powerful incentives to move away from it,” he observed. “Switching from Pap tests annually to every three years has been the USPSTF recommendation since 2012, but patient and provider preferences have been hard to change. I expect the same phenomenon will delay implementation of primary HPV screening every 5 years.” 

The editorialists underscored the need to expand access to these screening tools to indigent communities that receive sporadic and fragmented care at safety net healthcare facilities. “For the public health planner, the more inclusive screening menu provides a greater range of options creating more opportunities to tailor approaches to target populations,” they wrote. In the 2018 guidelines, the task force called for more research to improve access to screening and treatment across different populations and reduce disparities.