From the Journals

For HPV-negative women, longer screening intervals are effective

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Extending the screening interval: Is longer better?

The ultimate goal of cervical cancer screening is to minimize unnecessary procedures while maximizing identification of preinvasive disease. The recent article by Dr. Dijkstra and her associates provides 14-year follow-up for a national population-based cervical screening randomized trial.

The authors, who focused their analysis on patients older than age 40, describe how HPV results allow for a more targeted intervention triage than cytology alone. The study is impressive in its large patient cohort and extremely low detection rate of cervical cancer among HPV-negative patients in the intervention group. Their main argument stems from identifying an equivalent risk for CIN3+ between patients who were negative for HPV at 10 years and those with negative cytology at 5 years.

In the United States, current guidelines endorse cotesting for patients in this age group, with a negative cotest requiring repeat testing at 5 years. Changes to the screening protocol in the United States are often met with skepticism and slow uptake. This study certainly shows strong data to support HPV testing as the preferred option, but when does the time gap between screenings become too large, particularly for women whose only health care evaluation is through the gynecologist? Patients often think that not needing yearly Pap test equates to no need for routine examinations. We may be missing out on the opportunity to not only grow the patient-physician relationship, but also impact other aspects of the patients’ general health.

This article may not change practice, but it does add considerable weight to the growing literature on primary HPV screening, especially in an older population.

Ritu Salani, MD, is associate professor of gynecologic oncology at Ohio State University in Columbus. Robert T. Neff, MD, is a second-year fellow in gynecologic oncology at the university. They reported having no relevant financial disclosures.



It may be safe to extend cervical cancer screening intervals beyond 5 years, at least for women who are not infected with human papillomavirus.

The rate of cervical cancers was the same among HPV-negative women, whether they had gone through two or three rounds of 5-year exams using both HPV testing and cervical cytology, a large Dutch study has found. This suggests a longer period between screenings wouldn’t significantly increase the risk of letting new cancers go unnoticed, Maaike G Dijkstra, MD, and associates reported (BMJ. 2016;355:i4924. doi: 10.1136/bmj.i4924).

The picture, however, is very different for women with an HPV infection, the researchers noted. These women were 12 times more likely to develop cervical cancer and up to 29 times more likely to have a cervical intraepithelial neoplasia of at least grade 3 (CIN3+), compared with women who were HPV negative.

The findings bring a measure of reassurance to the Dutch population, the researchers wrote. The Netherlands intends to lengthen its cervical cancer screening interval to 10 years for HPV-negative women aged 40 years or older.

“HPV-negative women have a very low risk of CIN3+ in the long term, indicating that extension of the current screening interval in the Netherlands to 10 years seems justifiable,” wrote Dr. Dijkstra of the VU University Medical Centre, Amsterdam, and her colleagues. “For HPV positive, triage negative women, the long term risk of CIN3+ was too high to support an extension of the screening interval beyond 5 years.”

The study assessed the 14-year risks of cervical cancer and CIN3+ in 43,339 women aged 29 years and older. As per national guidelines, all women underwent cervical cancer screening every 5 years, resulting in three rounds. They were randomized to receive HPV and cytology testing or cytology only.

Among HPV-negative women in the double-screening group, the cumulative cervical cancer incidence was 0.03% after round two and 0.09% after round three – not a statistically significant difference.

After round three, cervical cancer incidence among HPV-negative women with negative cytology (double negative) was similar to that among cytology-negative women from the control group after round two.

In the cytology-only group, the rates among negative women were 0.09% after round two of screening and 0.19% after round three.

“This indicated that a negative HPV test provides longer reassurance against cervical cancer than negative cytology,” the researchers noted.

HPV-positive women, however, faced much higher risks, regardless of the screening protocol. Even with negative cytology, they were 12 times more likely to have a cancer by round three than HPV-negative women. The risk of CIN3+ was up to 29 times higher. Even HPV-positive women with negative cytology, negative HPV 16/18 genotyping, and negative repeat cytology faced a 10-fold increased risk of CIN+3, the researchers reported.

Dr. Dijkstra reported having no financial disclosures. Several of the coauthors disclosed financial relationships with various pharmaceutical companies.

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