Several countries are poised to extend human papillomavirus (HPV) screening intervals from every two to three years to an interval of at least five years, but new data suggests HPV screening programs with long intervals should be implemented with risk stratification.
The study, “Safety of extending screening intervals beyond five years in cervical screening programmes with testing for high risk human papillomavirus: 14 year follow-up of population based randomised cohort in the Netherlands,” was published in The BMJ. The study shows that HPV-negative women have low long-term incidences of high-grade cervical cancer and may be screened at higher intervals, but those who are HPV-positive and tested negative in their cytology should continue being tested at shorter, two- to three-year intervals.
A number of studies have shown that HPV screening leads to earlier detection of cervical intraepithelial neoplasia (CIN) grade 3 or worse, than cytology. CIN is the premalignant transformation of the cervical tissue, meaning that HPV screening leads to a better prevention of cervical cancer than cytology.
Currently, women are first tested for HPV. If their test comes back positive, they are then recommended to undergo cytology or be tested for HPV16 and HPV18, the high-risk subtypes. This is a means of preventing over-referral to colposcopy and overuse of biopsies, the authors said.
“The screening program could be further improved by reducing the number of screening rounds,” Maaike G Dijkstra, MD, obstetrics and gynaecology resident from the VU University Medical Centre, in Amsterdam and colleagues wrote.
To address this issue, several countries (Australia, Italy, Netherlands, New Zealand, Sweden, the U.K., and the U.S.) are now preparing to extend the screening intervals from every two to three years, to an interval between five and seven years. However, clinicians are concerned that the increase in cancer-screening intervals will lead to an increase in the number of cancers appearing during those long periods.
To evaluate the safety of extending the screening interval beyond five years, Dijkstra and her team conducted a 14-year follow-up of 43,339 women included in the POBASCAM trial (ISRCTN20781131), aged 29 to 61, who tested negative for HPV and/or cytology test.
Women were assigned randomly to receive both HPV and cytology testing (intervention), or cytology testing only (control), being screened at baseline, after five years, and after 10 years.
Results revealed the cumulative incidence of cervical cancer (0.09%) and CIN3+ (0.56%) among HPV-negative women in the intervention group after three rounds of screening, were similar to that among women with negative cytology in the control group after two rounds of screening (0.09% and 0.69%, respectively).
Compared to younger women, HPV-negative women at least 40 years old had a 72.2% lower CIN3+ incidence.
Importantly, the researchers found that in HPV-positive women with negative cytology, HPV 16/18 genotyping, or repeat cytology, the incidence of CIN3+ was 10.4 times higher than in HPV-negative women. That suggests HPV-positive women are at higher risk of developing cervical cancer, even if their cytology comes back negative, and should be screened at shorter intervals.
“Long term incidences of cervical cancer and CIN3+ were low among HPV-negative women in this study cohort, and supports an extension of the cervical screening interval beyond five years for women aged 40 years and older,” the researchers wrote.
“HPV-positive women with subsequent negative cytology, HPV16/18 genotyping, and/or repeat cytology have at least a fivefold higher risk of CIN3+ than HPV-negative women, indicating that HPV-based programs with long intervals (greater than five years) should be implemented with risk stratification,” they added.