Our study estimated the incidence and cost of oropharyngeal cancer (including base of tongue, tonsil) and anogenital cancer (anal, vulvar, vaginal, penile cancer) in 2013–2016 using nationally representative sample in Korea.
During the study period, 8,022 new patients were identified, and the total number of patients with five cancers increased from 1,952 in 2013 to 2,101 in 2016. The incidence rate for male oropharyngeal cancer was the highest among the five cancers, and oropharyngeal cancer showed a significant gender gap, with males vs. females being 3.1 vs. 0.7 per 100,000 as of 2016, respectively. A previous Korean study also showed that the number of male patients was higher than that of female patients, which is similar to our study . Additionally, the incidence of male oropharyngeal cancer increased from 2.7 in 2013 to 3.1 in 2016, whereas that of female and other cancers was stable during the study period. The incidence rate of oropharyngeal cancer associated with HPV is increasing in Asian countries such as Singapore, Taiwan and developed countries such as Northern Europe, Australia, and the United States, and the incidence rate is 2–3 times higher in males than in females [25–28], which is consistent with our study.
The total incidence-based medical cost for oropharyngeal and noncervical anogenital cancer in 2013–2016 was 133,964,586 USD, bringing a significant economic burden to Korea, and greatly increased from 27,803,613 USD in 2013 to 38,864,428 USD in 2016. Vaginal cancer and anal cancer demonstrated the steepest increase in medical costs during 2013–2016 (12,515 USD in 2013 to 18,636 USD in 2016 (49%); 10,662 USD in 2013 to 15,911 USD in 2016 (49%), respectively). The cost of oropharyngeal cancer was the highest among the five cancers, which is consistent with a previous study . Oropharyngeal cancer is anatomically complex and difficult to operate compared to other cancers, and reconstruction may be added to restore function . Therefore, the cost of surgery is expected to be higher than that of other cancers. Additionally, cetuximab has been reimbursed since 2014, which is in line with a sudden increase in expenditure in 2014, whereas only chemical drugs are reimbursed for the rest of the other cancers . Moreover, because the head and neck are the organs that are used for speaking and swallowing food, it is closely related with patients’ quality of life, and there is a risk of having a disability even after treatment such as neck resection . Therefore, aggressive prevention of oropharyngeal cancer should be considered to improve health outcomes as well as reduce financial burden. Regression analysis was conducted in oropharyngeal cancer and anal cancer to estimate gender-specific annual cost, since those two cancers can occur in both genders. The cost of oropharyngeal cancer for males was significantly higher than that of females based on the regression analysis (p < .001), both in univariate and multivariate analysis. It is not surprising that annual costs were significantly higher as years pass and for the patient who had experienced surgery. Interestingly, our analysis showed that patients under 65 and a lower CCI had significantly higher cost based on the multivariate analysis, using both the GLM and OLS models. Since we defined cancer patients based on primary or secondary diagnosis only, patients who are defined to have respective cancers based on the tertiary or beyond diagnoses codes are not included in our analysis. Since those patients are likely to be older and have higher CCI scores, our study might underestimate the cost of patients with higher CCI or older age; thus, our study should be interpreted with caution.
A previous prevalence-based cost-of-illness study estimated the health care costs of HPV-associated diseases in Korea using claims data in 2015 and suggested that the number of patients for anal, vulvar, vaginal and penile cancer was 2,071, 588, 383, and less than 300, respectively . Since we estimated the new patients of each cancer, our estimates are lower than the prevalence of each cancer, yet the trend observed in their study is consistent with what we have estimated in the number of incidences of each cancer. Since the definitions of diseases included in oropharyngeal cancer in our study and previous study are different, the direct comparison of oropharyngeal cancer was difficult. The prevalence-based healthcare costs per patient in a previous study were estimated at 4,096 USD for oropharyngeal, 3,737 USD for vaginal, 3,370 USD for vulvar, 2,807 USD for anal and 2,169 USD for penile in 2015. The cost of oropharyngeal cancer was the highest, and the cost of penile cancer was the lowest, which is consistent with our study. The prevalence-based cost estimated in a previous study and the incidence-based cost estimated in our study are nearly five times different. This difference appears to be due to the high initial treatment cost of cancer after the first diagnosis [12, 13, 15, 16]. As such, the cost of incidence and prevalence-based cost are quite different and should not be confused.
The HPV associated annual cost per patient in 2016 was estimated to be 14,536 USD for vaginal cancer, 14,002 USD for anal cancer, 6,736 USD for oropharyngeal cancer, 5,049 USD for penile cancer and 3,226 USD for vulvar cancer, respectively, after accounting for the HPV attributable fraction . Overseas countries estimated the incidence of HPV-associated noncervical cancers. A Danish study estimated the annual incidence rate of HPV-associated anogenital cancers (anal, penile, vaginal, vulvar cancer) in Denmark in 2004–2007 and suggested that the incidence rates for anal, penile, vaginal and vulvar cancer were 1.9, 1.7, 0.9 and 3.6 per 100,000 persons, respectively , which was higher than what we observed in our study (1.5, 0.3, 0.5, 0.6 for each year 2016, respectively) . According to another Danish study, the incidence of anal cancer in Denmark has been steadily increasing, presumably due to patterns of change in sexual behavior . The sex culture of Korea has changed rapidly in recent years, and the trend of an open sex culture is spreading due to the rapid westernization of social culture, which explains our increasing trend . Therefore, appropriate prevention should be considered to prevent the increase in the incidence rate of HPV-associated disease in Korea. The incidence of oropharyngeal disease was estimated in Singapore, and the incidence per 100,000 persons of oropharyngeal squamous cell carcinoma was 2.66 for males and 0.72 for females in 2008–2012 . In comparison with the results of our study, the incidence per 100,000 persons of oropharyngeal cancer in 2013 was 2.7 for males and 0.7 for females, similar to that of the Singaporean study. The Singaporean study suggested that Singapore has a potential burden of male oropharyngeal cancer and that changing current HPV precautions that focus on cervical cancer may also help prevent male oropharyngeal cancer.
Our study has some limitations. The burden of disease may be underestimated because non-medical costs, such as transportation costs, caregiver costs, and productivity losses are excluded. Second, we defined patients based on the primary or secondary diagnosis, so disease recorded after secondary diagnosis was excluded. Therefore, the result of estimating medical costs may vary according to such operational definition. Although large data sets are used, the CCI used in the regression analysis may depend on these operational definitions. However, our study has the following strengths. The HIRA claim data include almost 98% of Korea's entire population, which is representative of the Korean population. In addition, 99% of HIRA claims data are claimed through electronic data interchange (EDI) . Therefore, it is expected that almost all patients who used medical services for oropharyngeal and anogenital cancer (anal, vulvar, vaginal, penile cancer) during 2013–2016 would be included . To our knowledge, our study is the first to estimate the incidence-based medical cost for oropharyngeal (including base of tongue, tonsil) and anogenital cancer (anal, vulvar, vaginal, penile cancer) in Asia. It is also the first to show that the incidence-based medical costs of oropharyngeal and anal, vulvar, vaginal, and penile cancers are increasing in Korea. The incidence-based medical cost estimation results in our study are particularly useful when considering disease prevention and can be useful as a basis for providing estimates of the potential costs [36, 37].