Age at last screening and remaining lifetime risk of cervical cancer in older, unvaccinated, HPV-negative women: a modelling study

Talía Malagón, Shalini Kulasingam, Marie Hélène Mayrand, Gina Ogilvie, Leah Smith, Céline Bouchard, Walter Gotlieb, Eduardo L. Franco

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

Abstract

Background: There is a paucity of empirical evidence to inform the age at which to stop cervical cancer screening. The recommended age to stop screening generally varies between age 50–70 years worldwide. However, cervical cancer incidence and mortality remain high in older women. We used a Markov model of cervical cancer screening to estimate the remaining lifetime risk of cervical cancer at different ages and with different exit screening tests, with the aim of informing recommendations of the age at which to stop cervical cancer screening in developed countries. Methods: For this modelling study, we developed a state transition (Markov) model of cervical cancer natural history and screening. We developed, calibrated, and validated our model using Canadian provincial registries and survey data. To simulate an age-structured population in the model, a new cohort of 236 564 women (one fifth of the population of Canadian women aged 20–24 years in 2012) entered the model every year and were successively modelled in parallel. Successive cohorts entered the model at age 10 years, creating an age-structured population of women aged 10–100 years. Women who had a total hysterectomy were excluded from the analyses. We calibrated our model to human papillomavirus (HPV) infection and cancer incidence with data from Statistics Canada, which compiles the data from 13 individual provincial registries. We chose a three-stage progressive cervical intraepithelial neoplasia model to include differences in management and treatment decisions depending on lesion severity. We modelled infections with four high-risk HPV groups: HPV16 and HPV18; HPV31, HPV33, HPV45, HPV52, and HPV58; HPV35, HPV39, HPV51, HPV56, HPV59, HPV66, and HPV68; and a generic group of other potentially oncogenic HPVs. We estimated 5-year, 10-year, and remaining lifetime risk of cervical cancer for older, unvaccinated women who stopped screening at different ages and underwent different screening tests. Findings: Cervical cancer incidence excluding women with hysterectomies underestimated the incidence of cervical cancer in women with a cervix by up to 71% in women aged 80–84 years. Our model predicted that women without HPV vaccination who have been never screened have a 1 in 45 (95% percentile interval 1 in 32 to 1 in 64) lifetime risk of cervical cancer. Perfect adherence (100% of women screened) to cytology screening every 3 years between the ages of 25 years and 69 years could reduce the lifetime risk of cervical cancer to 1 in 532 women (95% percentile interval 1 in 375 to 1 in 820) without HPV vaccination. Increasing the age at which women stopped cytology screening from 55 years to 75 years led to incremental decreases in cancer risk later in life. A 70-year old woman whose screening history was unknown had an average remaining lifetime risk of 1 in 588 (<1%; 95% percentile interval 1 in 451 to 1 in 873) if she stopped screening. Her remaining lifetime risk at age 70 years was reduced to 1 in 1206 (2·0 times reduction; 95% percentile interval 1 in 942 to 1 in 1748) if she had a negative cytology test, 1 in 6525 (12·9 times reduction; 95% percentile interval 1 in 3167 to 1 in 18 664) if she had a negative HPV test, and 1 in 9550 (18·1 times reduction; 95% percentile interval 1 in 4928 to 1 in 23 228) if she had a negative co-test for cytology and HPV. Interpretation: Cervical cancer risk reductions might be achieved by screening with cytology up to age 75 years, although with diminishing returns. A negative exit oncogenic HPV test or negative HPV test plus cytology correlates with a low remaining lifetime cervical cancer risk for unvaccinated women with a cervix after the age of 55 years. Funding: Canadian Institutes of Health Research.

Original languageEnglish (US)
Pages (from-to)1569-1578
Number of pages10
JournalThe Lancet Oncology
Volume19
Issue number12
DOIs
StatePublished - Dec 2018

Bibliographical note

Funding Information:
TM reports research funding from the Canadian Institutes of Health Research (CIHR) during the conduct of the study. ELF reports research funding from CIHR during the conduct of the study, grants from Merck, grants and non-financial support from Roche, personal fees from Merck, and personal fees from GlaxoSmithKline outside the submitted work. M-HM is a recipient of a Fonds de Recherche du Québec—Santé clinical research scholar salary award. CB has received speaker honoraria from Merck Canada and is a member of the advisory boards for Merck Canada and Pfizer Canada. GO reports grants from Roche Molecular Systems and Gen Probe outside the submitted work. All other authors declare no competing interests.

Funding Information:
This work was supported by the Canadian Institutes of Health Research (operating grant 68893, team grant 83320, and catalyst grant HSE-151297 to ELF, and Fellowship Award to TM) .

Publisher Copyright:
© 2018 Elsevier Ltd

Fingerprint

Dive into the research topics of 'Age at last screening and remaining lifetime risk of cervical cancer in older, unvaccinated, HPV-negative women: a modelling study'. Together they form a unique fingerprint.

Cite this