Worldwide, liver cancer is the fifth most common cancer among men, the ninth most common cancer among women, and the second most common cause of cancer death for men and women combined [1]. In the United States, each year approximately 31,000 new cases of liver cancer are diagnosed and almost 25,000 people die from the disease [2]. Liver cancer is more common in men than women, and among Asian/Pacific Islander, Hispanic and American Indian/Alaska Native populations compared with other racial and ethnic groups [2]. The five-year net survival rate for liver cancer is 14.8% [3]. Liver cancer incidence has been increasing in the United States since the mid-1970s [4]. A major factor contributing to the increase in hepatocellular carcinoma (HCC), the most common type of liver cancer, is a high prevalence of chronic hepatitis C virus (HCV) infection among “baby-boomers,” or those born during 1945 through 1965 [4]. Increases in obesity and type II diabetes over the past several decades have also likely contributed to the increasing liver cancer trend, because of their association with non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) [5]. Other notable risk factors for development of HCC include chronic infection with hepatitis B virus (HBV) and alcoholic cirrhosis [6].

Due to recent advances in treatment, hepatitis C is now curable with short and easily tolerable courses of treatment [7]. Most cases of HBV infection can be prevented through vaccination [8]. The extent to which these preventive interventions are adopted within populations is unclear. The Centers for Disease Control and Prevention’s (CDC) National Comprehensive Cancer Control Program (NCCCP) is well positioned to raise awareness of the growing incidence of liver cancer and the critical role prevention efforts can play in reducing future incidence and liver cancer-related morbidity and mortality. Recipients of NCCCP funding develop specific plans to address the burden of cancer in their population. Current recipients of funding include all 50 states, the District of Columbia, and several tribes and territories [9].

In 2010, a review of NCCCP plans for liver cancer prevention activities revealed that most plans did not address the connection between chronic HBV and/or HCV infections and liver cancer, and only a few plans mentioned prevention activities to reduce the burden of liver cancer [10]. In order to increase uptake and identify liver cancer prevention activities that can be included in NCCCP plans for the broader cancer control community, we undertook a review of the current literature related to public health liver cancer prevention efforts to inform the NCCCP, and also conducted an updated review of NCCCP plans. The findings from this review will inform the development of an Action Plan on liver cancer prevention for the NCCCP, which will assist programs and the cancer community with the adoption and uptake of relevant, non-clinical, promising practices for the prevention of liver cancer.

Investing in surveillance of hepatitis B and hepatitis C is essential to the prevention of liver cancer, suggesting the need for the NCCCP to continue to help with tracking vaccine uptake, but also identifying those requiring counseling and linking them to care. Although the literature recommends strategic incorporation of evidence-based interventions into hepatitis C treatment implementation efforts, the recommendation did not specify which interventions to implement [12]. Therefore, the NCCCP could be engaged in identifying strategies within their population for retaining people with HCV infection in care even after successful completion of treatment, as well as for continued surveillance of liver cancer (for those with advanced liver disease at the time of hepatitis C treatment) and of reinfection.

The findings focused on the need to modify individual and community level factors of the Health Behavior Framework to promote hepatitis B testing [27]. NCCCPs are actively engaged in increasing knowledge and awareness on hepatitis B vaccination, and improving health professionals’ knowledge related to the increased use of the vaccine. However, there is an opportunity for the NCCCP to help with culturally tailoring the intervention approaches and messages for their respective populations. Delivering lecture-based hepatitis B education has been shown to significantly improve knowledge of hepatitis B and its transmission [20–21], suggesting that the NCCCP can facilitate the modification of existing educational campaigns to incorporate this promising intervention in their population. Additionally, the development and dissemination of effective patient and provider education programs, and professional training programs to state cancer programs and key clinical staff is essential in order to help them deliver better services to infected patients. The NCCCP can help implement these programs through the development of awareness campaigns and community outreach initiatives within their population. NCCCPs could ensure that these educational programs promote education and knowledge about the risk factors, prevention, and transmission of HCV, importance of testing and counseling, medical management of the condition to prevent chronic liver disease, and identification of facilities that offer integrated care and service delivery for infected individuals [14]. NCCCPs could also ensure that these educational programs are conducted in a culturally sensitive manner. Additionally, the training programs developed and delivered by NCCCPs could include information on the prevention, detection, and medical management of persons infected with HCV and HBV, in order to help them deliver better services to infected patients [14].

Hepatitis B vaccination is the most effective way to prevent HCC, the most common type of liver cancer, associated with chronic HBV infection [11]. In 2008, the CDC recommended hepatitis B testing for persons born in countries where HBV infection prevalence is ≥2%, which includes much of sub-Saharan Africa and Asia. In 2014, the United States Preventive Services Task Force (USPSTF) also recommended hepatitis B testing for these populations [35]. Therefore, another promising practice for the prevention of infection and liver cancer for those individuals who are susceptible to HBV infection includes completion of the vaccination series. Hsu and colleagues [21] found that age and race/ethnicity were associated with immunization status, therefore NCCCP awardees, through a needs assessment, can reach out to those populations that are less likely to receive vaccinations. Providing a discounted fee for the hepatitis B vaccine has been shown to improve completion of the vaccination, [17] suggesting that NCCCPs could partner with local community organizations to offer similar incentives, or promote existing vaccination programs.

In 2017, the National Academies of Sciences, Engineering, and Medicine, published a phase two report on a national strategy for the elimination of hepatitis B and C [7]. In the report, the authors stated that diagnosing 90 percent of cases, bringing 90 percent of those to care, and treating 80 percent of those for whom treatment is indicated, would result in a cumulative 50 percent reduction in mortality by 2030, averting over 60,000 deaths. The same level of diagnosis, care, and treatment would reduce incident liver cirrhosis by about 45 percent and new cases of HCC by a third [7]. Thus, NCCCPs can play a critical role in reducing the development of liver cancer in patients with HCV-related cirrhosis by helping to deliver and implement prevention programs to high-risk patients. These programs could include testing for hepatitis C in all persons with risk factors for infection and treatment for all HCV-infected persons. NCCCP-supported programs could expand their primary care partnerships to include local clinics that serve populations at high risk for viral hepatitis infection (e.g., individuals who inject drugs or are homeless) to screen them for hepatitis C and link them to care. The major challenge in scaling up hepatitis C treatment is currently increasing testing to identify those infected and reducing payer imposed restrictions to treatment access [36]. NCCCP awardees could develop new or strengthen existing partnerships within their state health departments’ hepatitis program so that they can work in a more coordinated manner to reach high risk individuals and increase their awareness of liver cancer and the need for increased prevention efforts. Risk-based testing guidelines were issued in 1998 by CDC, to recommend hepatitis C testing in persons at high risk for HCV infection, including past or current injection drug users and those in receipt of a blood transfusion before 1992. In 2012, the CDC recommended 1-time hepatitis C testing for individuals born during 1945 through 1965 (i.e., “baby boomer” generation) regardless of ascertainment of other risk factors [37] because of the high prevalence in that population (~3% versus ~1% in the general populations). The following year, the USPSTF issued similar recommendations [38]. These populations were targeted because there is evidence of an increased burden of HCV infection and liver cancer-associated mortality among this birth cohort. Even though baby boomers’ risk is elevated, a 2013 National Health Interview Survey indicated that only 12.3% reported receiving hepatitis C testing [39]. These recommendations provide a unique opportunity for NCCCP awardees to identify settings appropriate for viral hepatitis vaccination, screening, and treatment in communities, as well as to work with partners and state and local health departments to support standard case finding measures and ensure follow-up and monitoring of people with HBV and HCV infections.

Two additional promising practices found in the literature include EHR-based provider prompts and the use of patient navigators. Hsu and colleagues [22] indicate that EHR-based provider prompts can increase hepatitis B testing in patients when compared to usual care; thus, EHR prompts are a promising intervention that can be utilized by the NCCCPs. Lastly, the use of patient navigators to take participants to a healthcare provider for testing, or for follow-up if tested positive, is another promising practice that could be adopted by the programs.

This review was subject to several limitations. First, among studies identified in the published and grey literature, some intervention details were missing such as information on the necessary resources needed to implement the intervention successfully. Because this information was missing, we made “informed inferences” about the types of resources necessary for intervention implementation. Second, interventions identified in the published literature focused on the individual level, which may be less relevant to the NCCCP given the program’s emphasis on increasing population-based health. Third, there is a lack of generalizability in most of the intervention studies identified in the published and grey literature. Almost all focused on Asian American subpopulations (e.g., foreign-born Chinese adults); and, sample sizes were small. Fourth, our review of the literature focused on public health programs related to liver cancer and may have missed articles more clinical in nature and focused only on specific forms of liver cancer (e.g., HCC). Fifth, we did not control for the limitations of reviewed studies related to research design including reporting bias, selection bias, accuracy, and reliability of identified risk factors, cost and budget limitations, lack of randomization of participants to a non-intervention group to assess the effectiveness of event activities, and incomplete data/loss to follow-up. Sixth, NCCCP plans are updated on different cycles, thus, some plans may not be as recent as other plans. Therefore, our findings may not reflect newer liver cancer prevention and control activities developed or being planned by some NCCCP awardees. Lastly, we did not review grantee progress reports; therefore, information related to grantee progress toward meeting objectives was not assessed.

In conclusion, promising practices in the areas of surveillance, primary prevention through immunization, knowledge and awareness of infection status, and improved viral hepatitis treatment services, have the ability to reverse increasing liver cancer trends. NCCCP awardees are including hepatitis-related activities in their cancer plans; however, there is a need for awardees to diversify their interventions. CDC has supported the development of a number of technical assistance resources in order to assist programs to either begin or build upon their ongoing work. Examples include a viral hepatitis and liver cancer national prevention profile, state specific prevention profiles, as well as a worksheet to help public health professionals address the burden of viral hepatitis, all of which can be found on the CDC liver cancer website [40]. The findings from this review of published literature and NCCCP plans will inform the development of an Action Plan on liver cancer prevention for the NCCCP. This plan will assist programs with the adoption and uptake of promising practices for the prevention of liver cancer within their respective populations.