Cancer screening aims to reduce overall mortality by prevention or early detection of invasive disease. This issue of Cancer Forum, launched to coincide with the 2014 World Cancer Congress in Melbourne, focuses on the latest developments in cancer screening. These developments include policy updates for the established screening approaches for prevention of breast, cervical and colorectal cancer. For example, in response to the rapid impact of HPV vaccination, Australia’s established cervical screening program is now preparing to implement a major transition from cytology to primary HPV screening. National roll-out of two-yearly bowel cancer screening in people aged 50-74 years is underway and expected to be completed by 2020. Also discussed in this issue are the challenges in assessing the balance of benefits and harms of cancer screening (especially for breast screening and prostate specific antigen testing) and the future potential of screening more targeted populations for cancer, including screening high risk people for lung cancer, screening Indigenous populations for oral cancer and screening newly incident cases of colorectal cancer for Lynch Syndrome, so that at-risk family members can be identified. A common theme that emerges is the ongoing challenge, as well as the opportunity, posed by the introduction of new screening technologies, and the need to ensure that the benefits, cost-effectiveness and harms associated with use of these technologies are comprehensively evaluated and communicated effectively to clinicians and consumers.
The Australian mammography screening program was introduced as a joint Commonwealth and state/territory initiative in 1991. Australian evaluation studies suggest a breast cancer mortality reduction from mammography screening in Australia that is generally higher than estimated from the original field trials (reported by an International Association of Research on Cancer expert group to be about 35% for screening participants aged 50-69 years, and following a meta-analysis of data for all ages, to be about 25%). More research is needed to broaden the evidence on over-detection. Intervention research is also needed to determine the comparative effectiveness and cost-effectiveness of digital breast tomosynthesis in the Australian screening environment.
The National Health Service Breast Screening Program began operations in 1988. Good quality was achieved by the mid-1990s, by which time the program was screening one million women per year. Criticism of the program grew in the first decade of the 21st century. Originally it was alleged lives were not saved, but this moved on to alleging that only a few lives were saved, and that many more were damaged by overdiagnosis. In 2012, an independent review of the breast screening program was commissioned, which concluded that the program saved about 1300 lives per year and should continue. However, for each life saved, three women were diagnosed with cancer who might not otherwise have had such a diagnosis. Following the review, the information leaflet sent to women was revised to take account of the new calculations of benefits and harms. The program is now conducting a major trial of screening of women 47-49 and 71-73 years, involving sending additional invitations at each end of the routine 50-70 year age group. It is also considering the evidence about introduction of tomosynthesis and how to meet the challenge of the retirement of the cohort of staff who were appointed at the start of the program.
There are few topics in medical science that arouse as much controversy – and as much passion – as the role of mammography in breast cancer screening. Part of the reason for continued debate lies within the complexity of the audiences for any recommendations made. The recent emphasis has been upon the individual weighing personal benefit and risk. Public health recommendations however, are based upon the overall population-based estimates of risk and benefit. In particular, population-based screening programs and public messaging must, by definition, come to conclusions about the best course of action based on a weighting of the risks and benefits for ‘average’ women in a specific population. This overview provides a window into the current analyses of the risk and benefits of mammography screening, and of the impact of these debates on considerations of programmatic screening. It examines current information on the perceived benefits and risks, the recent move towards individualised decisions of risks and benefits, and the role of public health messaging and population-based programs within this context.
Australia implemented a national, publicly-funded vaccination program against human papillomavirus (HPV) in 2007. Initially the program targeted females aged 12-13 years, with catch-up of females aged 13-26 years to 2009. Since 2013, males aged 12-13 years have also been included in the program, with a two-year catch-up for males aged to 14-15 years. Three-dose coverage in 12-13 year-old females is approximately 71%, and estimated coverage rates over the female catch-up program were 70% in the school-based program (females 12-17 years) and ~30-50% in the primary-care-based program (female 18-26 years). Early data on cervical abnormalities, genital warts and HPV prevalence in cervical specimens suggest the impact of this program has been rapid and substantial, and that it also provided some indirect protection for young unvaccinated females and young males. Almost seven million doses of HPV vaccine have been delivered in Australia, and the vaccine safety profile remains favorable and comparable to that of other vaccines. Ongoing monitoring of coverage, impact and safety will be critical for the ongoing success of the program. It is important to emphasise that female cohorts offered vaccination should continue to attend cervical screening, since current generation vaccines do not protect against all types of HPV implicated in cervical cancer.
We now know that persistent cervical infections by certain types of human papillomavirus (HPV) designated as high-risk, carcinogenic or cancer-associated, cause virtually all invasive cervical cancer. The discovery of oncogenic HPV as the necessary cause of invasive cervical cancer has led to revolutionary advances in invasive cervical cancer prevention, including the development of sensitive molecular HPV testing for cervical cancer screening. Using high-risk HPV testing for the primary screen shifts the use of the Pap test from the general population to those women at risk of cervical cancer, high-risk HPV positives. In high-resource settings, using high risk HPV testing as the primary cervical cancer screening test could increase the efficiency of current screening programs, more effectively identify women at risk for adenocarcinoma, and combined with self-collection, reach medically unserved populations that experience a disproportionate burden of invasive cervical cancer.
The National Cervical Screening Program in Australia has been stable and successful for more than two decades. Nevertheless, the environment in which the program operates has been profoundly disrupted by the introduction of the equally successful National Human Papilloma Virus (HPV) Vaccination Program. The ‘Renewal’ (or review) of cervical screening is designed to ensure that the success of the screening program continues and that all Australian women, HPV vaccinated and unvaccinated, have access to a cervical screening program that is based on current evidence and best practice. Renewal has involved an assessment of the evidence for the benefits and harms of various screening pathways and a modelled assessment to inform the likely efficacy of the various proposed screening pathways in vaccinated populations. The findings indicated that the effectiveness of the program could be increased, while the expenditure could be decreased, if HPV tests were used in place of cytology. In April 2014, the Medical Services Advisory Committee recommended that Australia move to a five yearly screening program using an HPV test with partial genotyping for HPV16/18 as the primary screening test, commencing at age 25 and with an exit test between the age of 70 and 74. At a research level, a major trial, Compass, designed to evaluate primary HPV screening in a partially vaccinated population, will generate empirical evidence against which to test the modelled predictions of the Renewal. Together, the evidence review, modelling and ongoing research provide a framework for continuous improvement of the cervical screening program and the potential for further declines in cervical cancer in Australian women.
There is a consensus among relevant peak professional bodies, government and non-government organisations in Australia, that Australian clinical practice guidelines for prostate specific antigen (PSA) testing and early management of test-detected prostate cancer are needed. Work is underway on systematic reviews of the evidence. Guideline development based on systematic review covers clinical questions relating to underlying risk of prostate cancer, PSA testing, investigation of men with positive tests and early management choices, the last relating particularly to choice among active surveillance, watchful waiting and immediate definitive treatment. National Health and Medical Research Council processes are being followed and the council’s approval of the finished product will be sought. Public consultation on draft guidelines is expected to start in December 2014 and the council’s approval is expected to be obtained in June 2015 or later. Planning for guideline dissemination and implementation is essential.
Results from international randomised controlled trials have been inconsistent as to whether prostate specific antigen (PSA) testing is associated with a mortality benefit. However, the PSA test is commonly used to test asymptomatic men for prostate cancer in Australia. The harms, including additional diagnostic evaluation and exposure to treatment regimens and their side-effects, may be substantial. It is possible that less frequent testing, a clearly identified target population and careful consideration of thresholds and triage protocols for men with elevated PSA could be used to achieve a more advantageous balance between the benefits and harms of testing. It is not practical to assess a wide range of potential testing strategies via clinical trials, since any testing-associated benefits for prostate cancer-specific mortality would take years to accrue and would also be logistically challenging. Furthermore, the benefits, harms and cost-effectiveness of testing in Australia depend on several factors specific to the local context, including testing uptake and the risk profile of the population. Mathematical modelling will therefore play an important role in synthesising the data from international trials with known local testing, disease and treatment variables. Here, we review the international literature on models of PSA testing and conclude that investment in a carefully calibrated and validated population model of prostate cancer in Australia will provide an important platform for estimating the impact of future candidate strategies for testing for prostate cancer.
The United States Preventative Services Task Force is an independent panel of non-Federal experts in prevention and evidence-based medicine that reviews scientific studies and makes recommendations on screening and prevention interventions. The panel is widely respected for its rigour and basing its recommendations on the scientific evidence. In late 2013, the task force published a recommendation on screening for lung cancer using low-dose computerised tomography. They recommend annual screening in adults, aged 55 to 80 years, who have a 30 pack year smoking history and currently smoke or have quit within the past 15 years. They also recommend screening be discontinued once a person has not smoked for 15 years, or develops a health problem that substantially limits life expectancy or the ability or willingness to have curative lung surgery. The statement also stresses the need for rigorous quality controls to minimise the harms associated with lung screening and resultant diagnostic procedure.
The term ‘oral cancer’ encompasses neoplastic lesions involving the lip, oral and oropharynx. The vast majority of these lesions are squamous cell carcinomas. Risk factors include tobacco and alcohol use and, particularly for oropharyngeal cancers, exposure to human papillomavirus. Visual screening for oral cancers in the mouth necessitates an appreciation of the presentation of oral lesions that have an increased risk of malignant transformation. Recent evidence reviews by the US Preventative Services Task Force and the Cochrane Collaboration have concluded that at the current time, there is insufficient evidence to recommend oral cancer screening in the general population. However, because of the potentially serious outcomes for patients and impact on quality of life, opportunistic visual screening opportunities should be part of general oral examinations for patients visiting health professionals, particularly dental practitioners.
Lynch Syndrome is characterised by the development of colorectal, endometrial and other cancers, often at a young age. It is caused by constitutional mutations of DNA mismatch repair genes and cancers that arise in this setting are mismatch repair deficient, as demonstrated by loss of the relevant mismatch repair protein and microsatellite instability. In theory, universal screening of all index colorectal cancers for mismatch repair deficient should identify individuals who are at higher than population risk of carrying a constitutional mutation in the mismatch repair genes. A health economic evaluation in the UK found that this type of screening strategy applied to individuals under the age of 51 years was highly cost effective. In Australia, some centres routinely test all colorectal cancer for mismatch repair deficient, however there is currently no systematic national approach to screening. Given the cost effectiveness of universal screening is dependent on uptake of constitutional testing by the index case and their relatives, we suggest that research into the determinants and barriers to uptake of constitutional testing is a high priority. Further, given that the health care context can influence the assessment of cost-effectiveness, we propose that the UK economic evaluation also needs to be undertaken in an Australian context.