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5-Year Interval for Cervical Cancer Screening Safe in HPV-Negative Women

— U.K. study also supports accuracy of HPV testing versus cytology

Ƶ MedicalToday
A photo of literature from the NHS regarding the Cervical Screening Programme.

Women ages 24 to 49 who initially test negative for the human papillomavirus (HPV) can be safely screened for cervical cancer at 5-year intervals, according to results from a U.K. study.

Using data from the first and second rounds of the English HPV screening pilot study, the researchers found that women younger than age 50 with a negative first-round HPV test result had a significantly lower risk of having cervical intraepithelial neoplasia grade 3 or worse (CIN3+) 3 years later in the second round (adjusted OR 0.26, 95% CI 0.23-0.30), as well as a lower risk of interval cancers (adjusted HR 0.44, 95% CI 0.23 to 0.84), compared with cytology testing (Pap smear).

The results "support the English Cervical Screening Programme's planned extension of the screening interval from three to five years for HPV negative women younger than 50 years and align with practice in other countries," Matejka Rebolj, PhD, of King's College London in England, and colleagues wrote in .

Among women under 50, 1.21 in 1,000 had CIN3+ detected after a negative HPV screen compared with 4.52 in 1,000 after a negative cytology. Risk of incident CIN3+ detected at the second screening round 5 years after a negative HPV test was even lower in women older than 50 compared to 3 years after a negative HPV test in women younger than 50 (adjusted OR 0.46, 95% CI 0.27 to 0.79), the team reported.

"This finding suggests that the current interval of five years at age 50 years and older could also be extended," the authors wrote.

The currently invites women ages 25-49 every 3 years and ages 50-64 every 5 years to have cervical screening.

In an , Karen Canfell, PhD, of the University of Sydney in Australia, and colleagues noted that these intervals are efficient for cytology screening, and that the resulting reductions in cervical cancer mortality were similar to those in countries with shorter intervals.

However, the editorialists added, studies have shown that a negative HPV test result is associated with a very low risk of CIN3+ over 6 or more years, "which has led to a recommended screening interval of at least five years in most policy contexts."

"Safely increasing the screening interval is an important contributor to the cost effectiveness of HPV screening," Canfell and co-authors continued. "Recent World Health Organization guidelines, for example, position HPV as the primary screening approach and recommend an interval of five or 10 years for the general population (without HIV infection). England's shorter intervals in younger women are a legacy from traditional cytology based screening."

In the U.S., the screening for cervical cancer every 3 years with cervical cytology alone in women ages 21 to 29. For women 30 to 65, the recommendation is for screening every 3 years with cervical cytology alone, every 5 years with high-risk human papillomavirus (hrHPV) testing alone, or every 5 years with hrHPV testing in combination with cytology. USPSTF notes, however, that is currently in progress.

The American Cancer Society (ACS) in 2020 that differ from those of the USPSTF. They recommend cervical cancer screening with an HPV test alone every 5 years for everyone with a cervix from age 25 until age 65. If HPV testing alone is not available, people can get screened with an HPV/Pap co-test every 5 years or a Pap test every 3 years.

"What the authors are showing here is that a single HPV test offers greater protection at 5 years than cytology at 3 years, and this is why we recommend HPV testing alone because it has greater accuracy for detecting high-risk HPV infections, which are associated with developing cervical cancer," ACS's senior vice president of cancer screening, Robert Smith, MD, PhD, told Ƶ. "This is consistent with what's been shown previously, and it's great to have this additional confirmation in especially large studies like this."

He noted that the ACS does not recommend a longer interval for women age 50 and older, as suggested by Rebolj and colleagues in their study. "There's a lot to be said for the simplicity of a program that says women should be tested every 5 years," Smith said.

He pointed out, however, that once they pass their reproductive years many women stop getting screened for cervical cancer.

"That's a big problem, because the current testing guidelines offer that women who have no history of CIN3 or greater and have had consecutive normal, technically satisfactory screening tests in the 10 years leading up to the age of 65 can stop screening for cervical cancer," Smith noted.

"But if you don't have that record you need to keep getting screened for cervical cancer," he continued. "If you were to ask most women if they would like to keep screening for cervical cancer after the age of 65, I'm sure most would say no. But it's critically important that their healthcare providers make sure they build this record of normal tests so that they have the option to stop screening at 65."

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    Mike Bassett is a staff writer focusing on oncology and hematology. He is based in Massachusetts.

Disclosures

Rebolj noted that she was provided Public Health England funding for the epidemiological evaluation of the pilot study, and for an unrelated study; and that she is a member of the Public Health England Laboratory Technology Group, the HPV Development Group, and the HPV Self-sampling Operational Steering Group and Project Board. She also reported attending meetings with various HPV assay manufacturers, and received a fee, paid to her employer, for a lecture at Hologic.

Co-authors reported relationships with Cepheid, Euroimmun, GeneFirst, SelfScreen, Hiantis, Seegene, Roche, Abbott, and Hologic.

Primary Source

The BMJ

Rebolj M, et al "Extension of cervical screening intervals with primary human papillomavirus testing: observational study of English screening pilot data" BMJ 2022; DOI:10.1136/bmj-2021-068776.

Secondary Source

The BMJ

Canfell K, et al "HPV screening for cervical cancer is reaching maturity" BMJ 2022; DOI: 10.1136/bmj.o1303.