Cigarette smoking and nasopharyngeal cancer: a systematic review and meta-analysis| Tabaccologia

Abstract

Introduction: Nasopharyngeal cancer is a relatively rare but aggressive malignancy with a significant impact on patients’ quality of life. This systematic review and meta-analysis aim at providing an updated estimate of the association between cigarette smoking and the risk of nasopharyngeal cancer.

Methods: A systematic review and meta-analysis of all published epidemiological studies on the association between cigarette smoking and nasopharyngeal cancer risk, published up to 2023, was performed. This review was conducted using an innovative methodology combining an umbrella review and a traditional systematic review. Pooled estimates of relative risk (RR) and 95% confidence interval (CI) according to smoking status were calculated using random-effects meta-analytic models.

Results: A total of 40 studies were included in the meta-analysis. Pooled RR estimates of nasopharyngeal cancer were 1.63 (95% CI: 1.41-1.89) for current smokers and 1.28 (95% CI: 1.09-1.49) for former smokers, compared with never smokers.

Conclusions: This meta-analysis provides robust evidence on the association between cigarette smoking and the risk of nasopharyngeal cancer, highlighting the importance of smoking cessation promotion and tobacco control policies for the prevention of this malignancy.

Introduction

Nasopharyngeal cancer is a malignant neoplasm that originates in the epithelial cells lining the floor and surface of the nasopharynx. Its incidence is relatively low, with just over one case per 10,000 people diagnosed each year worldwide [1]. Its geographical distribution, however, varies considerably, with the regions of East and South-East Asia having the highest incidence rates [2]. Nasopharyngeal cancer has significant consequences on patients’ quality of life and is known to be quite aggressive, with an estimated five-year survival rate of 63% [3].

The exact pathogenesis of nasopharyngeal cancer remains unknown to date, given the complexity of risk factors involved. Among these, the most explored in the literature are contact with the Epstein-Barr virus, heredity, alcohol consumption and exposure to environmental chemicals [2, 4-6].

One of the most widely studied risk factors associated with the development of cancers of the respiratory tract, including the nasopharynx, is cigarette smoking [7-10]. It contains a wide range of harmful chemicals, including numerous known carcinogens, which can enter the upper respiratory tract. These substances can cause DNA damage and promote the development of cancer cells [10].

Among the studies investigating cancer risks associated with cigarette smoking, the majority treat nasopharyngeal cancer exclusively as part of cancers of the head and neck complex, upper aero-digestive tract or pharynx. There is therefore a need to update the evidence on this topic, to provide new comprehensive and accurate estimates of the quantification of the risk of nasopharyngeal cancer associated with cigarette smoking.

Objective

The aim of this meta-analysis is to provide the most accurate and up-to-date estimate of the association between cigarette smoking and nasopharyngeal cancer risk.

Methods

A systematic review and meta-analysis of all published epidemiological studies (case-control or cohort studies) on the association between cigarette smoking and nasopharyngeal cancer risk was conducted. This review was conducted using an innovative methodology that combines an umbrella review and a traditional systematic review, with the aim of identifying the highest number of published articles on the topic [11]. The umbrella review identified 57 reports, which included systematic reviews, meta-analyses, pooled analyses or reports from international bodies, regarding the association between cigarette smoking and the risk of cancers located anywhere in the upper aero-digestive tract. From these reports, all original articles that specifically addressed nasopharyngeal cancer were extracted. Subsequently, an update of the scientific literature, which included studies on the association between cigarette smoking and risk of nasopharyngeal cancer published from 2016 until 2023, was conducted in order to identify any new relevant publications. After combining the original articles considered in the reports with those identified through the literature update, a screening process was carried out based on a priori-defined eligibility criteria [11].

Aggregate estimates of relative risk (RR) and 95% confidence interval (CI) according to smoking habit were then calculated using random-effects meta-analytic models.

Results

After the screening process, a total of 40 original articles were included, of which 33 were case-control studies and 7 were cohort studies. The studies covered a time span from 1982 to 2021 and provided data on more than 15,000 subjects with nasopharyngeal cancer. Of the included articles, 17 studies provided a measure of association, or sufficient information to derive it, on the risk of nasopharyngeal cancer for current smokers, 15 for former smokers, and 38 for ever smokers (current smokers and former smokers combined), compared to never smokers.

Figure 1 and 2 show the RRs of nasopharyngeal cancer, overall and stratified by study design, for current and former smokers, respectively, compared with never smokers.

The pooled estimates of the RR of nasopharyngeal cancer for current smokers compared to never smokers were 1.63 (95% CI: 1.41-1.89) for all studies combined, 1.62 (95% CI: 1.37-1.91) for the 12 case-control studies and 1.95 (95% CI: 1.22-3.10) for the 5 cohort studies (p-value of heterogeneity between study designs equal to 0.46).

The pooled estimates of RR of nasopharyngeal cancer for former smokers compared to never smokers were 1.28 (95% CI: 1.09-1.49) for all studies combined, 1.33 (95% CI: 1.11-1.59) for the 12 case-control studies and 1.07 (95% CI: 0.78-1.46) for the 3 cohort studies (p-value of heterogeneity between study designs equal to 0.24).

The pooled estimates of RR of nasopharyngeal cancer for ever smokers compared to never smokers were 1,62 (95% CI: 1,41-1,87) for all studies combined, 1.64 (95% CI: 1.41-1.91) for the 34 case-control studies and 1.46 (95% CI: 1.00-2.12) for the 4 cohort studies (p-value of heterogeneity between study designs equal to 0.24).

Discussion

The systematic review and meta-analysis described in this project provides the most up-to-date, comprehensive and accurate evidence of the association between cigarette smoking and nasopharyngeal cancer risk. The application of an innovative study design for the identification of original articles made it possible to include in the review several studies that had not been identified in previous meta-analyses. This meta-analysis, with 40 studies included, therefore represents the largest study conducted until now on the association between cigarette smoking and nasopharyngeal cancer. In the future, updated estimates of RR associated with cigarette smoking will also be calculated for the other cancer sites of the upper aero-digestive tract, applying the same research methodology.

The results show a significant increase in the risk of nasopharyngeal cancer associated with cigarette consumption. Specifically, a 63% increased risk was found in current smokers, a 32% increased risk in former smokers, and a 62% increased risk in ever smokers, compared to never smokers. No significant differences were found between estimates from case-control and cohort studies. These data confirm and reinforce the conclusions of previous systematic reviews and meta-analyses on the topic [7,8], unequivocally underlining that cigarette smoking is one of the most important risk factors for the development of nasopharyngeal cancer.

Although not shown in this report, dose-response analyses for the associations between nasopharyngeal cancer risk and selected cigarette smoking-related characteristics show an increasing linear trend in smoking intensity and duration and a decreasing linear trend in time since cessation. This underlines the importance of considering even moderate cigarette consumption as a significant risk factor. It also suggests that the risk of nasopharyngeal cancer gradually decreases after smoking cessation, even though it takes almost 20 years to return to the risk level of a never smoker.

The promotion of cigarette smoking cessation remains a priority in Italy and worldwide. Despite significant progress in raising awareness about the harms of tobacco, the prevalence of smokers in Italy still exceeds 20% [12]. The results of our systematic review and meta-analysis provide further evidence of the harmful effects of cigarette smoking. Primary prevention through smoking cessation programmes and tobacco control policies therefore remains crucial in the fight against cigarette smoking-associated malignancies, including nasopharyngeal cancer.

In conclusion, this meta-analysis highlights the importance of avoiding cigarette smoking in order to prevent the development of nasopharyngeal cancer, emphasising that even moderate consumption can significantly increase the risk. It is also crucial to promote cigarette smoking cessation in Italy in order to protect public health and reduce the burden of tobacco-related diseases.

Figures and tables

Figure 1.Forest plot and relative risks (RR) of nasopharyngeal cancer for current smokers (CS) versus never smokers (NS), overall and aggregated by study design. CI: confidence intervals; M: males.

Figure 2.Forest plot and relative risks (RR) of nasopharyngeal cancer for former smokers (FS) versus never smokers (NS), overall and aggregated by study design. CI: confidence intervals; M: males.

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