HPV infection linked to doubled risk of thyroid cancer

By Hugo Francisco de SouzaReviewed by Susha Cheriyedath, M.Sc.Jan 4 2024

In a recent study published in the journal Scientific Reports, researchers used a nationwide case-control study of Taiwanese residents to investigate the association between human papillomavirus (HPV) and thyroid cancer. Analyses of the 3,062 thyroid cancer patients and 9,186 healthy controls revealed that individuals with a prior HPV infection had more than double the likelihood of developing thyroid cancer than those without the infection (odds ratios 2.199 for HPV patients). This research presents the first concrete evidence of a carcinogen for thyroid cancer, the most common endocrine cancer and a growing concern worldwide.

Study: Association of thyroid cancer with human papillomavirus infections. Image Credit: Naeblys / Shutterstock

What do we know about thyroid cancer?

Thyroid cancer refers to the growth and development of malignant (cancerous) cells in the thyroid gland, a butterfly-shaped gland at the base of the neck. Despite being the most common endocrine cancer in the world today, thyroid cancer and especially its causative agents remain poorly understood. Alarmingly, the prevalence of this potentially lethal disease has been rising rapidly. In the United States of America (US) alone, thyroid cancer incidence rates have more than tripled over the past three decades, with current reports revealing that 45,000 new cancer cases are discovered within the country annually.

The thyroid gland is an essential endocrine organ whose secretions govern normal breathing, heart rate, body temperature (homeostasis), and nervous system function. Malignancies of this gland, though treatable, may result in severe disruptions in these bodily functions, leaving survivors with life-long comorbidities. Despite intensive recent research aimed at unraveling the underlying causes of thyroid cancers, a definitive carcinogen remains elusive. The current clinical and scientific consensus is that thyroid cancers arise due to a combination of genetic, environmental, and behavioral factors.

Human papillomavirus (HPV) is a sexually transmitted virus and the most common sexually transmitted infection (STI) globally. Despite the existence of numerous vaccines against HPV, 43 million people were estimated to be infected by the virus in 2018 alone. While severe HPV infections result in the development of warts and scarring around the mouth and genital areas, the virus' actual danger lies in its carcinogenicity – HPV (including asymptomatic infections) has been identified as the root cause of numerous cancers and is estimated to be responsible for 3% of female, and 2% of male cancers worldwide.

Recent research has identified HPV particles in thyroid nodules (both benign and malignant), but the association between the virus and thyroid cancer remains unexplored.

"As the role of human papillomavirus in the development of thyroid cancer presents an intriguing possibility, this study aims to investigate the association of human papillomavirus infection with the development of thyroid cancer using a nationwide population-based study."

About the study

Data for the present study was collected from Taiwan's Longitudinal Health Insurance Database (2005) and consisted of ambulatory care claims, prescriptions, medical facility reports, and inpatient claims mandated by the Taiwanese government. Thyroid cancer and HPV infections were defined and recorded as per the International Classification of Diseases, Ninth Edition, Clinical Modification (ICD-9-CM) guidelines.

This case-control study included thyroid cancer patients above the age of 20 and healthy controls in a 1:3 ratio. Following cross-referencing thyroid cancer cases listed in the Insurance Database against the Taiwan Cancer Registry, 3,062 patients were identified as eligible for inclusion in analyses. Propensity score matching was used to identify 9,186 medically insured individuals without a history of thyroid cancer.

"Propensity score matching is a quasi-experimental method that allows us to construct an artificial control group by matching each patient with thyroid cancer with a non-thyroid cancer beneficiary of similar characteristics."

HPV infections were confirmed using positive polymerase chain reaction (PCR) tests. Statistical analyses comprised t-tests and chi-square tests to elucidate the differences in cases and controls based on medical and demographic data. Multivariate logistic regressions, corrected for participant anthropometrics and demographics (age, sex, geographic location, income, medical history, and urbanization level), were used to estimate the associations between HPV and thyroid cancer quantitatively. Odds ratios (ORs) were computed to quantify the risk of developing thyroid cancer following HPV infection.

Study conclusions

The present study found that patients infected with HPV were 2.199 times more likely to subsequently develop thyroid cancer compared to those without a history of the virus. This suggests a strong association between the two diseases and presents the first evidence of HPV as a thyroid cancer-inducing carcinogen. Propensity score matching and statistical analyses confirmed that no statistically significant differences between cases and controls exist, strengthening support for HPV as the driving force behind observed thyroid cancer incidence.

Despite the study being restricted to Taiwan, thereby limiting the generalization of these findings, this study may shine a light on the hitherto unexplained rise in thyroid cancer cases globally. Multivariate analyses revealed that computed ORs remain stable irrespective of age or sex, albeit these ORs are lower for thyroid cancers compared to other HPV-induced cancers.

"If further research confirms the link between human papillomavirus and thyroid cancer, human papillomavirus vaccinations could possibly be used as a preventive measure. While further research is needed to corroborate this association and understand the underlying mechanisms, our study emphasizes the potential role of human papillomavirus in the development of thyroid cancer and the clinical implications thereof. This study supports the necessity for clinicians, researchers, and public health practitioners to be aware of the possible connection between human papillomavirus and thyroid cancer."