Cervical Cancer Screening, Triage Strategies Put to the Test

Megan Brooks

May 14, 2019

Many different cervical cancer screening strategies are now recommended in the United States, but no single screening strategy is favored by all, and the benefits, harms, and costs of each option remain unclear.

A pair of studies published this week in JAMA Internal Medicine "will inform continuing efforts to improve the effectiveness of cervical cancer screening," writes Sarah Feldman, MD, MPH, of the Division of Gynecologic Oncology, Brigham and Women's Hospital, Boston, Massachusetts, in an invited commentary on the studies.

In an effort to contribute to policy discussions regarding "high-value" cervical cancer screening, George Sawaya, MD, of the University of California, San Francisco, and colleagues estimated quality of life and economic outcomes associated with 12 strategies by measuring screening preferences among a diverse group of 451 women and incorporating them into a cost-effectiveness analysis.

On the basis of their results, they say cytologic (Pap) testing every 3 years for women aged 21 to 29 years with either continued cytologic testing every 3 years or testing with a low-cost, high-risk human papillomavirus (hrHPV) test every 5 years "confers a reasonable balance of benefits, harms, and costs."

"The lowest cost strategy was cervical cytology every 3 years for women aged 21 to 65 when an HPV test was used to triage the common cytologic result of atypical squamous cells of undetermined significance (ASC-US)," Sawaya explained in a journal podcast.

"Even greater health gains could be achieved at a very reasonable cost by screening with one of our oldest strategies, which is cytology every 3 years with repeat cytology in 1 year with ASC-US," he said.

It's not too surprising that screening with the least costly and most specific test is the most cost-effective strategy. Dr George Sawaya

Co-testing (cytology together with hrHPV testing for primary screening) and primary hrHPV testing alone provided less health benefit at greater cost, he noted.

Given that cervical cancer screening begins early in life and ends relatively late in life — and is performed frequently in between — "it's not too surprising that screening with the least costly and most specific test is the most cost-effective strategy," said Sawaya.

One key take-away from this study is that "more is not always better," said Feldman, who participated in the podcast.

A Pap test alone every 3 years "remains a cost-effective and acceptable option for women; or also if we move to HPV testing, HPV alone every 5 years with appropriate triage is also acceptable to patients and cost-effective for low-risk women," said Feldman.

Dual Stain More Informative After HPV-Positive Test

The other study focused on efficient approaches for triage of HPV-positive women in cervical cancer screening.

Nicolas Wentzensen, MD, PhD, from the National Cancer Institute in Bethesda, Maryland, and colleagues evaluated the performance of the p16/Ki-67 dual stain (DS) and HPV16/18 genotyping for the triage of women aged 30 years or older whose primary HPV screening test result was positive. They focused on trade-offs between colposcopy referral and detection of precancerous lesions in clinical practice.

This prospective observational study was conducted within the cervical cancer screening program at Kaiser Permanente Northern California. It involved 3225 HPV-positive women who had undergone HPV and Pap cytologic testing and had received a valid DS result during the fall of 2015. Follow-up lasted until the end of 2018.

The results showed that triage of HPV-positive women with DS was more informative than triage using cytologic testing alone, with "equal immediate detection of precancerous lesions and substantially reduced referral to colposcopy," the Wentzensen team reports in their article.

"These findings suggest that DS can safely replace Papanicolaou cytologic testing as a triage strategy for primary HPV screening, and that retesting intervals in HPV16/18-negative women with negative DS results can be safely extended to 3 years," they conclude.

"Although the US Preventive Services Task Force recently endorsed primary HPV screening for women age 30 years or older who are at average risk for cervical cancer, at present there are no consensus guidelines for how to manage abnormal results. The dual stain method offers a promising approach to the next step in determining which women need further evaluation and management," Feldman wrote in her commentary.

"Ideally, early vaccination of children with the HPV vaccine will eventually substantially reduce the risk of cervical and other HPV-related cancers, but this is going to take a long time to materialize," Feldman said in the podcast. "In the meantime, screening technology is rapidly advancing. Knowing who, how, and how often to screen women, as well as making sure all women are appropriately screened, will remain ongoing challenges as we go forward."

Neither study received commercial funding. A complete list of disclosures of authors' relevant financial relationships is available with the original articles.

JAMA Intern Med. Published online May 13, 2019. Sawaya et al, Abstract; Wentzensen et al, Abstract; Commentary

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