Background: Over the past two decades, prescription opioid use has risen sharply in many countries worldwide. While the short-term consequences of the opioid crisis, such as overdose deaths and toxicities, are well documented, its long-term public health effects remain poorly understood. In 2020, opium consumption was classified as “group 1 - carcinogenic to humans” by the IARC Monographs, based on sufficient evidence for cancers of the lung, larynx, and bladder. This classification has raised concerns about the carcinogenic potential of prescription opioids, given their close similarities in chemical composition and mechanisms of action. Although experimental and registry-based studies suggest a possible link between prescription opioid use and increased cancer risk, rigorous evaluation has been limited by the paucity of detailed opioid exposure data and insufficient statistical power in prospective cohort studies. To address these limitations, the Opioid Cohort Consortium (OPICO) was established at IARC in 2021, in collaboration with 35 scientists from 20 institutes worldwide.
Objectives: The overarching aim of OPICO is to build the largest and most robust international resource for investigating opioid use and its long-term health effects. The specific aims are to: (1) generate detailed, longitudinal data on prescription opioid use in large prospective cohort studies through linkage with national medication dispensing or prescription records; (2) harmonize data on opioid use, demographics, comorbidities, key confounders, and cancer outcomes across diverse populations worldwide; and (3) investigate associations between prescription opioid use and cancer incidence and mortality, as well as other chronic health outcomes.
Methods: OPICO harmonizes data from 28 sources, including prospective cohort studies, cancer registries, medication dispensing or prescription records, and electronic health records across the United States, Europe, and Australia. The consortium includes nearly 1.7 million individuals followed for a median of 10 years. OPICO applies novel methodologies to harmonize opioid medications across seven coding systems used in five jurisdictions and to standardize exposure to more than 29,000 opioid-containing medications into a small set of internationally comparable metrics, including cumulative oral morphine equivalents (OME). This framework enables evaluation of associations between prescription opioid use and site-specific cancer incidence, including comparisons of strong versus weak opioids, natural versus semi-synthetic versus synthetic opioids, analgesic versus non-analgesic opioids, and routes of administration. Analyses will employ advanced causal inference approaches, including target trial emulation and time-dependent models. First results from OPICO are expected in late 2026 / early 2027.
Conclusions / Implications:  OPICO is expected to generate the most comprehensive and methodologically rigorous evidence to date on whether prescription opioid use contributes to cancer risk. By addressing key sources of bias and leveraging large-scale prospective data, this project will substantially advance understanding of the long-term health consequences of opioid use. Findings from OPICO will have important implications for public health and clinical practice, informing opioid prescribing guidelines, cancer prevention strategies, and targeted early detection policies aimed at mitigating the potential future cancer burden associated with the ongoing opioid crisis.

Prospective cohort studies participating in the Opioid Cohort Consortium (OPICO)