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The International Agency for Research on Cancer monographs recently classified opium consumption as carcinogenic to humans in certain organs, raising concerns this may be due at least in part to the alkaloids opium contains (such as morphine and codeine). This systematic review investigated whether opioid exposure among cancer-free individuals is independently associated with the risk of future cancer incidence or cancer mortality. An electronic database search was conducted in PubMed, EMBASE, Web of Science, PsycINFO, International Pharmaceutical Abstracts, CINAHL and Scopus. Studies were included if they provided a statistical estimate of cancer mortality, cancer incidence, or cancer risk following opioid exposure. Study quality was assessed using the Newcastle\u2013Ottawa Scale. Study characteristics and outcomes were extracted and analysed in a descriptive narrative synthesis. There were 27 studies that met the inclusion criteria, representing a total of 4,542,745 participants. Twelve of the 27 were rated as high quality according to the Newcastle\u2013Ottawa Scale. The observed data is consistent with a small increase in the risk of cancer incidence or cancer mortality following opioid exposure, particularly in a subset of organs. There is, however, considerable uncertainty in the evidence given the substantial risk of bias in estimating the overall effect of opioid exposure on cancer outcomes in these studies. This review synthesises studies reporting cancer risk following opioid exposure and identifies the key methodological factors influencing ongoing uncertainty estimating the true effect. Rigorous epidemiological studies employing specific methods to minimize bias are warranted.<\/jats:p>","DOI":"10.1007\/s10555-025-10268-0","type":"journal-article","created":{"date-parts":[[2025,6,11]],"date-time":"2025-06-11T03:57:34Z","timestamp":1749614254000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Opioid use and the risk of cancer incidence and mortality: a systematic review"],"prefix":"10.1007","volume":"44","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0344-091X","authenticated-orcid":false,"given":"Shakti","family":"Shrestha","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5993-9050","authenticated-orcid":false,"given":"Holly","family":"Foot","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3972-7824","authenticated-orcid":false,"given":"Mahdi","family":"Sheikh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4895-7381","authenticated-orcid":false,"given":"Marie-Odile","family":"Parat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6802-6141","authenticated-orcid":false,"given":"Adam","family":"La Caze","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,6,11]]},"reference":[{"key":"10268_CR1","doi-asserted-by":"publisher","unstructured":"Snijders, R. 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