Program Director

Principal Investigator

Awardee Organization

University Of British Columbia
United States

Fiscal Year
Activity Code
Early Stage Investigator Grants (ESI)
Not Applicable
Project End Date

Addressing emerging health system priorities in cervical cancer prevention: determining optimal strategies for human papillomavirus test-based screening and triage

Cytology-based cervical cancer screening has been one of the most widely used and successful public health screening interventions in North America for decades. However, there are significant limitations to cytology alone as a screening test leading to thousands of preventable deaths. Highly sensitive molecular tools for detection of high-risk HPV, the cause of cervical cancer, are poised to transform cervical cancer screening programs in the United States and Canada. HPV-based screening is expected to reduce cervical cancer rates by 30% compared to cytology, due to improved sensitivity of HPV for pre-cancerous lesions. With the improved negative predictive value of HPV testing, screening intervals can be extended to every 4-5 years leading to substantial health care savings. Despite these advantages, the loss of specificity with HPV due to detection of transient infections that do not result in disease, particularly in young women, leads to twice the number of colposcopy treatments in otherwise well women. Thus, while preventing more cervical cancer cases with less frequent screening, HPV-based screening could lead to unintended harm for well women of reproductive age and unsustainable health care system costs if deployed without appropriate screening and triage algorithms. Triage with alternate molecular methods (ie. mRNA and genotyping) in HPV positive women or adopting these methods as a primary screen could offer improved specificity without reducing sensitivity. However, if, how and when to optimally integrate these tests into screening algorithms remains a critical knowledge gap globally. Aims: This study addresses priority questions from North American policy makers to evaluate the effectiveness of HPV testing with and without cytology co-testing, determine adverse effects of primary HPV testing, and to ultimately inform optimal screening algorithms for cervical cancer screening. Specifically the project will: 1) determine the long-term efficacy (120 months) of HPV-based primary screening after a single and multiple screening rounds, compared to cytology and co-testing; 2) determine the efficacy of 3 different HPV assays for triage of HPV positive specimens, and primary screening for precancerous lesions; 3) define parameters for modeling population and systems-level outcomes of different protocols on cervical cancer rates Methods: Participants of an established, highly engaged cohort (n=25,223) from a longitudinal randomized controlled trial comparing primary HPV testing to cytology will be followed to 120 months. Trial participants are currently 48 months years from baseline and have complete retrospective and prospective cervical cancer screening, colposcopy and treatment records, with linkage to a population-based cancer registry. Baseline negative women will be followed to 120 months though the centralized screening program, while a subset of participants will receive prospective additional HPV testing. Clinical endpoints, sensitivity/specificity and other parameters will be used for mathematic modelling & cost-effectiveness analysis.


  • Strang THR, Gottschlich A, Cook DA, Smith LW, Gondara L, Franco EL, van Niekerk DJ, Ogilvie GS, Krajden M. Long-term cervical precancer outcomes after a negative DNA- or RNA-based human papillomavirus test result. American journal of obstetrics and gynecology. 2021 Nov;225(5):511.e1-511.e7. Epub 2021 Jun 1. PMID: 34081897
  • Gottschlich A, van Niekerk D, Smith LW, Gondara L, Melnikow J, Cook DA, Lee M, Stuart G, Martin RE, Peacock S, Franco EL, Coldman A, Krajden M, Ogilvie G. Assessing 10-Year Safety of a Single Negative HPV Test for Cervical Cancer Screening: Evidence from FOCAL-DECADE Cohort. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 2021 Jan;30(1):22-29. Epub 2020 Oct 20. PMID: 33082202
  • Gottschlich A, Gondara L, Smith LW, Cook D, Martin RE, Lee M, Peacock S, Proctor L, Stuart G, Krajden M, Franco EL, van Niekerk D, Ogilvie G. Human papillomavirus-based screening at extended intervals missed fewer cervical precancers than cytology in the HPV For Cervical Cancer (HPV FOCAL) trial. International journal of cancer. 2022 Sep 15;151(6):897-905. Epub 2022 May 10. PMID: 35460070