Adapting cervical cancer screening to decreasing HPV infection rates

For cervical cancer screening, human papillomavirus (HPV)–based screening modalities detect significantly more abnormal cervical cells than traditional liquid-based cytology (LBC) approaches, according to a study in JAMA Network Open.

The decision analytical model, which simulated a population of 1,000 women aged 25 years and older with an HPV prevalence of 2%, also found that as the rate of HPV vaccination increased, HPV-based strategies resulted in fewer unnecessary colposcopies compared to LBC methods.

“The advent of the HPV vaccine has completely changed the landscape of cancer prevention, with roughly 5% of all cancer worldwide attributable to HPV infection,” said principal investigator David Grimes, PhD, an assistant professor of biomedical physics at Dublin City University in Dublin, Ireland.

The combination of the high efficacy of vaccination and the life-saving role of screening “means we can envision a future where the demon of cervical cancer is banished to the past,” Grimes told Contemporary OB/GYN®.

The investigators were inspired to better understand how screening needs to adapt to a decreasing incidence of HPV infection and quantifying the impacts of various modalities on screening outcomes, so that overscreening can be circumvented.

The 3 major outcomes and measures of the study were the number of cases of cervical intraepithelial neoplasia (CIN) grade 2 and 3 detected and missed, the number of false positives and the number of tests required to achieve a given level of accuracy.

Positive and negative predictive values of different modalities were simulated under varying levels of HPV vaccination and therefore HPV frequency.

HPV-based modalities detected 19% more true positives than LBC-based approaches: 89.9% HPV test sensitivity vs. 75.5% for LBC.

Cotesting also significantly reduced missed cases, detecting 29% more true positives than LBC alone: 19.5 per 1,000 women screened vs. 15.1 per 1,000 women screened.

But cotesting increased excess colposcopy referral by 94%: 184.4 false positives per 1,000 women screened vs 95.1 false positives per 1,000 women screened with LBC-based approaches.

Conversely, triage testing with reflex screening significantly reduced false positives by a factor of roughly 10; for example, HPV with LBC triage resulted in 9.6 false positives per 1,000 women screened.

Over a lifetime of screening, reflex strategies with appropriate test intervals maximized therapeutic efficacy. As HPV vaccination rates increased, HPV-based screening approaches resulted in fewer unnecessary colposcopies than LBC methods. For instance, HPV testing with 80% vaccine coverage produced 44.1 excess colposcopies per 1,000 women screened vs. 96.9 excess colposcopies per 1,000 women screened for LBC testing with 80% vaccine coverage.

“The results we obtained suggest that HPV-based screening approaches are highly effective at catching abnormal cases, whilst minimizing detrimental false positives and needless invasive colposcopies,” said Grimes, a visiting researcher in oncology at the University of Oxford in the United Kingdom. “What was perhaps surprising is just how effective reflex approaches are in reducing unnecessary interventions. Our results indicate these strategies could diminish false positives by a staggering factor of 10.”

The clinical ramifications of the study are broadly the same as physicians have long suspected, according to Grimes, which is “the HPV vaccine is life-saving, and that HPV-based modalities will ensure that screening programs remain robust and keep false positives to a minimum, even as vaccination rates increase in years to come.”

Overall, “the results of our modeling study are hugely encouraging,” Grimes said. “If HPV vaccine uptake remains high, we can dare to hope for a future where cervical cancer and related maladies are but bad memories. And that is something incredible.”

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Disclosure

Grimes reports no relevant financial disclosures.

Reference

  1. Grimes DR, Corry EMA, Malagon T, et al. Modeling cervical cancer screening strategies with varying levels of human papillomavirus vaccination. JAMA Netw Open. Published online June 30, 2021. 2021;4(6):e2115321. doi:10.1001/jamanetworkopen.2021.15321