IARC Monographs		WRCF Report
Category	Criteria	Category	Criteria
Sufficient	A causal relationship has been established between exposure to the agent and human cancer. That is, a positive relationship has been observed between the exposure and cancer in studies in which chance, bias and confounding could be ruled out with reasonable confidence.	Convincing	All of the following criteria are generally required: Evidence from more than one study type. Evidence from at least two independent cohort studies. No substantial unexplained heterogeneity within or between study types or in different populations relating to the presence or absence of an association, or direction of effect. Good quality studies to exclude with confidence the possibility that the observed association results from random or systematic error, including confounding, measurement error, and selection bias. Presence of a plausible biological gradient (‘dose response’) in the association. Such a gradient need not be linear or even in the same direction across the different levels of exposure, so long as this can be explained plausibly. Strong and plausible experimental evidence, either from human studies or relevant animal models, that typical human exposures can lead to relevant cancer outcomes.
Limited	A positive association has been observed between exposure to the agent and cancer for which a causal interpretation is considered to be credible, but chance, bias or confounding could not be ruled out with reasonable confidence.	Probable	All the following criteria are generally required: Evidence from at least two independent cohort studies, or at least five case–control studies. No substantial unexplained heterogeneity between or within study types in the presence or absence of an association, or direction of effect. Good-quality studies to exclude with confidence the possibility that the observed association results from random or systematic error, including confounding, measurement error, and selection bias. Evidence for biological plausibility.
		Suggestive	All the following were generally required: Evidence from at least two independent cohort studies or at least five case–control studies. The direction of effect is generally consistent though some unexplained heterogeneity may be present. Evidence for biological plausibility.
Inadequate	The available studies are of insufficient quality, consistency or statistical power to permit a conclusion regarding the presence or absence of a causal association between exposure and cancer.	No conclusion	The evidence might be limited by the amount of evidence in terms of the number of studies available, by inconsistency of direction of effect, by poor quality of studies (e.g. lack of adjustment for known confounders), or by any combination of these factors.
Evidence suggesting lack of carcinogenicity	There are several adequate studies covering the full range of levels of exposure that humans are known to encounter, which are mutually consistent in not showing a positive association between exposure to the agent and any studied cancer at any observed level of exposure. The results from these studies alone or combined should have narrow confidence intervals with an upper limit close to the null value (e.g. an RR of 1.0). Bias and confounding should be ruled out with reasonable confidence, and the studies should have an adequate length of follow-up.	Substantial effect unlikely	All of the following criteria are generally required: Evidence from more than one study type. Evidence from at least two independent cohort studies. Summary estimate of effect close to 1.0 for comparison of high vs low exposure categories. No substantial unexplained heterogeneity within or between study types or in different populations. Good quality studies to exclude, with confidence, the possibility that the absence of an observed association results from random or systematic error, including inadequate power, imprecision or error in exposure measurement, inadequate range of exposure, confounding, and selection bias. Absence of a demonstrable biological gradient (‘dose response’). Absence of strong and plausible experimental evidence, either from human studies or relevant animal models that typical human exposures lead to relevant cancer outcomes.

In Box 1, the criteria used in the IARC Monographs evaluations of carcinogenic risks to humans² and the WCRF Report on Nutrition and Cancer⁹⁴ are summarized. Although the categories of evidence do not match perfectly and the criteria vary in several important details, the two approaches are broadly in agreement. The WCRF criteria are more explicit than the IARC ones.