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Dutch Study Lends Support to Effectiveness of HPV-Based Cervical Screening

NEW YORK (GenomeWeb News) – Detection of pre-cancerous cervical lesions by DNA-based human papillomavirus screening translates into fewer high-grade lesions upon second screening five years later compared to conventional cytology screening, according to a study appearing online today in Lancet Oncology.

As part of a population-based study conducted in the Netherlands, researchers followed almost 45,000 women between the ages of 29 and 56 years over several years. Their goal was to assess the effectiveness of HPV DNA screening compared to cytology for finding pre-cancerous cervical lesions, known as cervical intraepithelial neoplasia, and preventing the development of more advanced CIN lesions or cancer.

Results from the Population-Based Screening Study Amsterdam, or POBASCAM, trial suggest a larger proportion of pre-cancerous lesions were identified in the group of women randomly assigned to receive HPV testing than in the cytology-based screening group. Women in the HPV testing group also had significantly fewer high-grade cervical lesions or cervical cancers in a subsequent round of screening five years later, they reported.

"Implementation of HPV DNA testing in cervical screening leads to earlier detection of clinically relevant CIN grade 2 or worse, which when adequately treated improves protection against CIN grade 3 or worse and cervical cancer," corresponding author Chris Meijer, a pathology researcher at the VU University Amsterdam, and colleagues wrote.

Previous studies have found that HPV testing offers a diagnostic advantage for finding CIN lesions that may develop into cervical cancer, the study authors explained, though the effectiveness of this screening for preventing the development of more serious cervical lesions and cervical cancers over several years is less well studied.

For the current study, researchers set out to determine which screening method corresponded to fewer high-grade lesions and/or cervical cancer cases in an initial screening event and in a subsequent round of screening five years later.

About half of the 44,938 women from a Dutch cervical screening program were randomly assigned to get HPV DNA-based cervical screening in the first round of testing, while the other half received conventional cytology-based screening.

During a second round of testing five years later, all of the women who were eligible and still participating in the study — 16,750 from the HPV testing group and 16,743 from the cytology group — received both HPV and cytology testing.

In the first round of screening, the researchers found a dozen cervical cancers in the DNA testing group and six in the cytology group. They also identified significantly more CIN2+ lesions in the groups screened for HPV DNA.

The improved detection of CIN lesions in the first round of testing appeared to help curtail the development of more advanced lesions or cancers in the DNA screened groups as well, the researchers reported.

In a round of testing five years later, women in the HPV testing group had significantly fewer CIN lesions that were classified as grade 3 or higher, with 88 CIN3+ lesions turning up in the DNA testing group compared to 122 in the cytology group.

In particular, the team found that HPV testing in the first screening round corresponded to fewer CIN lesions that were positive for a high-risk HPV strain called HPV16 in the second screening.

On the other hand, a similar number of CIN2+ lesions and of CIN3+ lesions without HPV16 were found in both the HPV DNA and cytology tested groups in the second round of screening.

"The protective effect against CIN grade 3 or worse in the second screen in the [DNA testing] group was largely attributable to HPV16," they reported. "HPV16 is the main genotype present in cervical cancer, hence, the early detection of HPV16-associated CIN grade 3 lesions is expected to eventually have an effect on long-term outcomes such as cancer morbidity and mortality."

Cervical cancer cases were less common in the HPV testing group as well, the team reported. They saw four cervical cancer cases in the group that got HPV testing initially and 14 cancer cases in the group that did not.

The team's age-based analyses, meanwhile, suggested HPV testing uncovered a comparable number of CIN2+ and CIN3+ lesions in women between the ages of 29 and 33 years old as it did in the women aged 34 to 56 years, leading investigators to argue that DNA-based screening did not lead to over-diagnosis of in the younger group.

"POBASCAM reinforces findings from cohort studies, clinical trials, and routine clinical practice by providing overwhelming evidence of the benefits of inclusion of HPV testing in screening programmes," National Cancer Institute cancer epidemiology and genetics researchers Hormuzd Katki and Nicolas Wentzensen wrote in an accompanying Lancet Oncology commentary article.

Nevertheless, the pair cautioned that further research is needed to understand whether a similar protocol would pan out the same way in populations with different baseline cancer rates, management strategies, and compliance levels.

Consequently, Katki and Wentzensen argued that "[t]he POBASCAM finding that is most immediately translatable to screening programmes worldwide is the [five] year screening interval for women 30 years and older who test HPV-negative with normal cytology."

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