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The Impact of Human Papillomavirus Infection on Skin Cancer: A Population-Based Cohort Study
Authors:Ming-Li Chen  Shuo-Hsuan Wang  James Cheng-Chung Wei  Hei-Tung Yip  Yao-Min Hung  Renin Chang
Affiliation:1. School of Medicine, Chung Shan Medical University, Taichung, Taiwan

Contributed equally.;2. School of Medicine, Chung Shan Medical University, Taichung, Taiwan;3. Division of Allergy, Immunology and Rheumatology, Chung Shan Medical University, Taichung, Taiwan

Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan

Graduate Institute of Integrated Medicine, China Medical University, Taichung, Taiwan

Contributed equally.;4. Management office for Health Data, China Medical University, Taichung, Taiwan

College of Medicine, China Medical University, Taichung, Taiwan

Institute of Public Health (Biostatistics), National Yangming University, Taiwan;5. Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan;6. Department of Emergency Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan

Abstract:

Background

This study investigated the correlation between a history of human papillomavirus (HPV) infection and skin cancer risk.

Materials and Methods

The study cohort comprised 26,919 patients with newly diagnosed HPV infection between 2000 and 2012; with the use of computer-generated numbers, patients without previous HPV infection were randomly selected as the comparison cohort. The patients in the HPV infection cohort were matched to comparison individuals at a 1:4 ratio by demographic characteristics and comorbidities. All study individuals were followed up until they developed skin cancer, withdrew from the National Health Insurance program, were lost to follow-up, or until the end of 2013. The primary outcome was subsequent skin cancer development. Cox proportional hazards regression analysis was used to analyze the risk of skin cancer with hazard ratios (HRs) and 95% confidence intervals (CIs) between the HPV and control cohort.

Results

The adjusted HR of skin cancer for patients with HPV relative to controls was 2.45 after adjusting sex, age and comorbidities. (95% CI, 1.44–4.18, p < .01). The subgroup analysis indicated that a patient with HPV infection had a significantly greater risk of skin cancer if they were aged >40 years. Notably, a risk of skin cancer was found in the group diagnosed with HPV within the first 5 years after the index date (adjusted HR, 3.12; with 95% CI, 1.58–5.54). Sensitivity analysis by propensity score, matching with balanced sex, age, and comorbidities, showed consistent results.

Conclusion

A history of HPV infection is associated with the development of subsequent skin cancer in Taiwanese subjects, and the risk wanes 5 years later.

Implications for Practice

In this Taiwan nationwide cohort study, there was a 2.45-fold increased risk of developing new-onset skin cancers for patients with incident human papillomavirus (HPV) infection, compared with the matched controls. Furthermore, the risk was noticeably significant among patients aged >40 years. A prominent risk of skin cancers was found in the group diagnosed with HPV within the first 5 years after the index date in this study. The results of this analysis may raise consensus on the effect of HPV infection on the risk of skin cancers. Clinicians are encouraged to implement prudently on the differential diagnosis of skin cancers and HPV prevention and treatment, especially in older patients.
Keywords:Human papillomavirus infection  Skin cancer  Cohort  Nonmelanoma skin cancer (NMSC)
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