To our best knowledge, this is the first study exploring the association between PM2.5 exposure and the OS of cervical cancer patients, especially in a relatively heavily polluted region. We found a stable relationship between higher PM2.5 exposure and poorer OS among cervical cancer patients. Even after being grouped by age and stages, the results still kept stable, although no significant associations were found in Figo I and Figo IV patients. Sensitivity analysis also excluded the probability that the results were dominated by the patients from some specific cities. Most results in this study accorded with the previous findings. Besides the elder age at diagnosis and higher clinical stages, we also found adenocarcinoma is a risk for OS of cervical cancer compared to squamous cell cancers, and single status was also identified as a risk, which is similar to the currently accepted results(Cohen et al. 2019).
So far, there has been some evidence about ambient air pollution exposure and cancer survival or survival-related symptoms, which includes the association between PM2.5 and the OS of lung, breast, liver, and ovarian cancer patients (Eckel et al. 2016, Hu. et al. 2013, Lurmann et al. 2017, Villanueva et al. 2021, Xu et al. 2013). But all these studies were based on Surveillance Epidemiology and End Results (SEER) cohorts or California population. And Eckel et al(Eckel et al. 2016) also found the effects of PM2.5 were larger in Asians, which reminds us of more attention on them. Therefore, our study provided important evidence in both Asian and developing countries' cancer patients, as well as in patients who resided in relatively heavily polluted areas. Further studies are still needed to explore the associations between PM2.5 and OS of other types of cancer patients, and also to confirm the current findings.
In addition to the association between the OS of cervical cancer patients and PM2.5 exposure, we also obtained some interesting findings from the subgroup analysis. First, both SCC and AC patients' OS was associated with PM2.5, but the HR of SCC is relatively larger. Although we did not find the explanation from the current literature, this finding is similar to Eckel et al. which found that in OS of lung cancer patients (Eckel et al. 2016). Second, the associations in stage I and stage IV patients were negative, but this might be reasonable. Villanueva et al. found the associations between PM2.5 and ovarian cancer survival were greater in patients with early stages(Villanueva et al. 2021), and the explanation by more cumulative PM2.5 exposure in these patients. But for cervical cancer patients, the survival rate of stage I patients during our study period was 96.2%, which may suggest not long enough periods to examine the associations on this population. As for stage IV patients, the most likely reason for negative results was the small sample size (n=87).
As mentioned above, the mortality of many types of cancers was reported to be associated with ambient air pollution exposure. The explanations may lie in higher incidences of cancer with higher exposure to ambient air pollution. However, it may not be suitable for cervical cancer that were mainly caused by high-risk HPV infection(Cohen et al. 2019). Therefore, more attention should be paid to the adverse effects on cervical cancer patients rather than before cancer. Unfortunately, due to the limited relevant studies, it is not clear if there is a causal relationship between PM2.5 and cancer survival, as well as the potential mechanism of how PM2.5 affects survival. But it is clear that ambient air pollution, especially PM2.5, has been classified as a carcinogen. That is to say, the carcinogenesis of PM2.5 including oxidative stress, DNA damage, cell proliferation, or epigenetic modifications may still work in survivors of cancers (Eckel et al. 2016). On the other hand, PM2.5 can directly harm respiratory function, which is particularly crucial for the recovery of cancer survival. Another potential reason for the association may be the short-term adverse effects of PM2.5 exposure. It has frequently been reported that short-term PM2.5 exposure was significantly associated with higher lung cancer daily mortality (Berger et al. 2018, Chung et al. 2021, Wang et al. 2019b), and the mortality displacement may also exist in the mortality of cancer patients.
Limitations of this study should be noted. First, our study was based on Liaoning cancer hospital, which is one of the best hospitals on oncology in Liaoning Province, where patients with low social-economic status might be less likely to come. Therefore as a single-center study, the enrollment of the patients might be biased due to the source of patients. Second, although we have designed the items of income levels and occupations, most patients refused to fill in this information. Therefore we could not control for SES-related confounders except for medical insurance in the cox-regression. Third, among all types of cancers, patients with cervical cancer have higher survival rates. As a result, cervical cancer-related studies also required a longer follow-up period. But due to no available Provincial PM2.5 data until 2014, we could only enroll patients diagnosed since then. Nevertheless, our finding still provides insights into the association between PM2.5 exposure and cervical cancer survival, which is of importance in both environmental sciences and oncology.