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HPV Test Intervals Could Be Safely Extended, Say Cervical Cancer Researchers

Doctor with an anatomical model of the cervix, uterus and ovaries
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Routine human papillomavirus (HPV) screening for cervical cancer may be safer at longer intervals than the current five-year recommendation, according to a new study published in Cancer Epidemiology, Biomarkers & Prevention.

The longitudinal study found that the risk of detecting cervical precancer eight years after a negative HPV result was comparable to the risk of testing after three years (the commonly recommended screening interval) following a negative cytology screening.

These results could better inform screening guidelines, with longer intervals between testing allowing for the realignment of resources to reach under-screened populations and encouraging follow-up testing.

The shift from cytology to HPV-based screening

Nearly all cervical cancers result from infection by the human papillomavirus (HPV). The growing availability of high-performance HPV tests and the HPV vaccine has led the World Health Organization (WHO) to call for the global elimination of cervical cancer as a public health concern by 2030.

Despite many high-income countries having established cytology-based screening programs, plenty still have cervical cancer incidence rates above the WHO’s elimination threshold goal. In the US, the incidence rate is currently 7.6 per 100,000 individuals, higher than the WHO goal of reducing new cases to 4 or less per 100,000 annually. To combat this, there is a need for high-sensitivity testing methods and optimized screening strategies.

The commonly recommended interval for routine cytology-based screening for cervical cancer is three years, whereas HPV-based screening is every five years. Several countries have recently begun transitioning from cytology to HPV-based screening for cervical cancer due to its higher sensitivity for detecting precancerous lesions.

“Due to the superiority of the HPV test to detect cervical precancers, the risk of cervical precancer is lower after a negative HPV test compared to after a negative cytology test,” Dr. Anna Gottschlich, assistant professor at Wayne State School of Medicine and the Barbara Ann Karmanos Cancer Institute and corresponding author of the study, told Technology Networks.

“HPV testing can offer practitioners and patients more confidence in their test results, as it detects more cervical precancer than cytology.”

As more countries transition from cytology to more sensitive HPV-based screening methods there has been concern about the safety of the extended interval, and whether cases could be missed.

“In this study, we investigated the risk of cervical precancer after either a negative primary HPV screen or a negative cytology screen to understand the differences in longitudinal risk for each screening strategy and to confirm that the extended interval for HPV-based screening is safe and effective,” said Gottschlich.

The study combined data from the Canadian HPV For Cervical Cancer Prevention (HPV FOCAL) trial and the follow-up FOCAL-DECADE study for the HPV screening cohorts. Data were used from the British Columbia Cervix Screening Program during the same interval for the cytology cohorts.

For each cohort, the cumulative risk of developing premalignant lesions of cervical cancer was calculated. The study looked at the risk of cervical intraepithelial neoplasia grades 2 (CIN2), 3 (CIN3), and higher (referred to as CIN2+ or CIN3+).

The risk of CIN2+ eight years after negative HPV tests was comparable to that of three years after negative cytology screens. After six years – longer than current five-year guidelines – HPV screens showed lower risk after negative tests. The risk of CIN3+ was also lower or similar in the HPV cohorts following eight years compared to the cytology cohorts after three years.

The detection of cervical precancer remained low after negative HPV screening during the 14-year duration of the study period and was significantly lower than normal cytology screening over that period. However, the risk for CIN2+ was higher for HPV screening for intervals longer than eight years compared to cytology after three years.

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“We found that the risk of cervical precancer 5 years after a negative HPV screen was in fact lower than the risk 3 years after a negative cytology screen (which is the current recommended interval for routine cytology-based screening),” explained Gottschlich.

“This study confirmed earlier findings that the extended 5-year interval between HPV screens does not increase risk of cervical precancer detection and is in fact, more protective.”

Recommendations for updated screening guidelines

These results could be used to better inform updated screening guidelines for cervical cancer. The researchers suggest that each country or province will need to determine the right guidelines given the resources at their disposal and extending intervals will require health system considerations to ensure adequate, continued engagement.

Longer intervals between testing, however, could allow for the realignment of resources to reach under-screened or unscreened populations. The researchers suggest that longer periods between screens could encourage follow-up testing.

Gottschlich concludes, “As the US transitions from cytology and co-testing to primary HPV screening, further research is needed to identify optimal implementation strategies, for example, the appropriate age to enter and exit screening programs and optimal triage strategies after an abnormal HPV screen.”

Dr. Anna Gottschlich was speaking to Blake Forman, Senior Science Writer and Editor for Technology Networks.

About the interviewee:

Dr. Anna Gottschlich is an assistant professor at Wayne State School of Medicine and the Barbara Ann Karmanos Cancer Institute. Gottschlich earned her PhD in epidemiologic sciences from the University of Michigan. Her research interests include the use of HPV testing and self-collection methods as a form of primary cervical cancer screening in low- and middle-income countries and under-screened populations.

Reference: Gottschlich A, Hong Q, Gondara L, et al. Evidence of decreased long-term risk of cervical pre-cancer after negative primary HPV screens compared to negative cytology screens in a longitudinal cohort study. Cancer Epidemiol Biomarkers Prev.  2024. doi: 10.1158/1055-9965.EPI-23-1587