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Smokers have a more than 50% increase in risk for squamous cell carcinoma of the skin, and the risk remained elevated, even among those who'd kicked the habit, researchers found.

Pooling of data from six studies revealed a "clear and consistent" association between smoking and cutaneous squamous cell carcinoma (OR 1.52, 95% CI 1.15 to 2.01), according to Jo Leonardi-Bee, PhD, and colleagues from the University of Nottingham in England.

However, the meta-analysis showed no association for nonmelanoma skin cancer in general (OR 0.62, 95% CI 0.21 to 1.79) or for basal cell carcinoma (OR 0.95, 95% CI 0.82 to 1.09), the investigators reported online in the Archives of Dermatology.

"This study highlights the importance for clinicians to actively survey high-risk patients, including current smokers, to identify early skin cancers, since early diagnosis can improve prognosis because early lesions are simpler to treat compared with larger or neglected lesions," Leonardi-Bee and colleagues stated.

Previous efforts to ascertain a possible relationship between smoking and skin cancer have had conflicting results, with some studies showing increased risks and others suggesting possible protective effects.

To assess the overall evidence, the researchers conducted a systematic review of the literature and a meta-analysis of 25 observational studies.

Closer examination of the squamous cell data determined that the risk differed according to smoking history:

• Ever having smoked, OR 1.61 (95% CI 0.83 to 3.12)
• Current smoking, OR 1.54 (95% CI 1.03 to 2.31)
• Past smoking, OR 1.21 (95% CI 0.94 to 1.56)

However, these differences did not fully account for the heterogeneity seen in the included studies, with I² statistics ranging from 28% to 86%.

Duration of smoking and the number of cigarettes smoked did not appear to influence risk for squamous cell carcinoma, with incidence rate ratios of 0.95 (95% CI 0.64 to 1.42) for more than 15 years of smoking and 0.90 (95% CI 0.60 to 1.36) for more than 20 cigarettes smoked daily.

The analysis of overall nonmelanoma skin cancer included four studies, with no risks being identified for any exposure:

• Present smoking, OR 0.62 (95% CI 0.21 to 1.79)
• Past smoking, OR 0.87 (95% CI 0.56 to 1.35)
• Ever smoking, OR 0.89 (95% CI 0.64 to 1.24)

Although single studies of basal cell carcinoma suggested that the risk tripled after 15 years of smoking (OR 3.31, 95% CI 1.42 to 7.74) and was higher among two-pack-a-day smokers (RR 1.5, 95% CI 1 to 2.1), other studies found no significant relationship for this type of cancer with years of smoking or quantity of cigarettes smoked.

One of the studies of basal cell carcinoma found that the risk associated with smoking was lower for the superficial multifocal subtype (OR 0.42, 95% CI 0.24 to 0.75) but did not differ for the nodular type (OR 1.20, 95% CI 0.77 to 1.87).

The researchers noted that discrepancies in risk could be expected for the subtypes of skin cancer.

"For example, [basal cell carcinoma] is slow-growing and locally invasive in contrast to cutaneous [squamous cell carcinoma], which is generally more aggressive and has the potential to metastasize," they explained.

Possible explanations for the association of smoking and squamous cell carcinoma could included the overall carcinogenic effects of tobacco, alterations to the immune system, and direct contact of smoke on the dermis, they noted.

A strength of the analysis was its generalizability, having been based on studies in 11 countries and including primarily middle-age and older individuals.

A limitation was the reliance in most studies on self-report of smoking.

In a "Practice Gap" note accompanying the meta-analysis, Joris A.C. Verkouteren, MD, and Tamar Nijsten, MD, PhD, of Erasmus Medical Center in Rotterdam, the Netherlands, stated that clinicians should remind patients of the myriad negative health effects of smoking -- including these cutaneous risks.

"In contrast to several risk factors of [squamous cell carcinoma], including prior UV radiation exposure, smoking is a modifiable factor," they pointed out.

"Thus, active risk reduction by smoking cessation is possible, especially since the meta-analysis suggests that current smokers are at the highest [squamous cell carcinoma] risk," the Dutch dermatologists wrote.