Background:
Lung cancer has emerged as a global public health problem and is the most common cause of cancer deaths by absolute cases globally. Besides tobacco, smoke infectious diseases such as human papillomavirus (HPV) might be involved in the pathogenesis of lung cancer. However, data are inconsistent due to differences in study design and HPV detection methods.

Aim:
A systematic meta‐analysis was performed to examine the presence of HPV‐infection with lung cancer.

Methods and Results:
All studies in all languages were considered for the search concepts “lung cancer” and “HPV” if data specific to HPV prevalence in lung cancer tissue were given. This included Journal articles as well as abstracts and conference reports. As detection method, only HPV PCR results from fresh frozen and paraffin‐embedded tissue were included. Five bibliographic databases and three registers of clinical trials including MEDLINE, Embase, Cochrane Library, and ClinicalTrials.gov were searched through February 2020. A total 4298 publications were identified, and 78 publications were selected, resulting in 9385 included lung cancer patients. A meta‐analysis of 15 case‐control studies with n = 2504 patients showed a weighted overall prevalence difference of 22% (95% CI: 12%‐33%; P < .001) and a weighted overall 4.7‐fold (95% CI: 2.7‐8.4; P < .001) increase of HPV prevalence in lung cancer patients compared to controls. Overall, HPV prevalence amounted to 13.5% being highest in Asia (16.6%), followed by America (12.8%), and Europe (7.0%). A higher HPV prevalence was found in squamous cell carcinoma (17.9%) compared to adenocarcinoma (P < .01) with significant differences in geographic patterns. HPV genotypes 16 and 18 were the most prevalent high‐risk genotypes identified.

Conclusion:
In conclusion, our review provides convincing evidence that HPV infection increases the risk of developing lung cancer.