Age appropriate screening for cancer: Evidence-based practice in the United States of AmericaTS Pandey
Department of Medicine, Division of General Internal Medicine, Section of Preventive Medicine, John H. Stroger Jr. Hospital of Cook County and Rush University Medical Center, Chicago, Illinois, USA
Correspondence Address: Source of Support: None, Conflict of Interest: None DOI: 10.4103/0022-3859.138813
Source of Support: None, Conflict of Interest: None
Cancer screening is a well established and integral part of routine care in the Western world including United States. Men and women are recommended to get age-specific screening for common cancers like breast, cervical, prostate, and colon. The goal of screening is primary and secondary prevention. Cancer prevention and early detection of cancers has been shown to improve survival rates and decrease mortality by prompt appropriate treatment. This article serves to outline the current guidelines in the United States for cancer screening and the evidence for them as well as discusses the possibility of a similar model of care in India as well as barriers to such a screening program for cancer. The evidence was mostly obtained from systematic reviews done by the United States Preventive Services Task Force guidelines and other peer institutions like American Cancer Society and Agency for Healthcare Research and Quality.
Keywords: Breast cancer, cancer, cervical cancer, colon cancer, mammogram, pap smear, screening, tobacco cessation
The concept of screening for cancer is fairly well established in the Western world where age appropriate tests are an integral part of routine care. Clinical practice guidelines are regularly published by peer institutes and groups to promote evidence-based practice in everyday care. The goal of screening is primary as well as secondary prevention in asymptomatic individuals - to prevent premalignant conditions from progressing to malignancy (as in the case of breast and colon cancers) and to promote early detection and treatment of cancer and disability limitation. In the United States of America, primary care physicians trained in Internal Medicine or Family Practice are the gatekeepers of healthcare. Health maintenance is an important part of their daily work and includes screening adult men and women for age-appropriate cancer. These cancers include breast, cervical, colon, and prostate cancer, the four most common cancers that afflict Americans (excluding skin cancer).
The United States Preventive Services Task Force (USPSTF) is an independent peer group in USA composed of national experts in prevention and evidence-based medicine that works to improve the health of all Americans by making evidence-based recommendations about clinical preventive services such as screenings, counseling services, or preventive medications.  This eminent panel consists of 16 volunteer members who are considered experts in Internal Medicine, Family Practice, Pediatrics, Behavioral Health, Obstetrics and Gynecology, and Nursing. The panel publishes clinical practice guidelines for primary care physicians based on the current literature and scientific evidence in the form of "Recommendation Statements". These guidelines are updated periodically when new evidence becomes available. Primary care physicians and health systems in USA generally follow these recommendations in their day to day practice. The USPSTF is supported by the Agency for Healthcare Research and Quality (AHRQ), which is the lead federal agency in USA charged with improving the quality, safety, efficiency, and effectiveness of health care for all Americans - it supports research that helps people make more informed decisions and improves the quality of health care services.
The notion of preventive care in India is still in its early stages and is mostly limited to executive health examinations. Screening for cancer is infrequently done. In this article, we attempt to update physicians about the practice of screening adults for common cancers in USA and the evidence on which the recommendations from the USPSTF are based.
Breast cancer is the most common cancer among American women after skin cancer and is the second leading cause of cancer-related deaths in the country. There were 230,480 new cases of invasive breast cancer and 39,520 deaths in 2011 in USA.  Significant reduction in mortality has been attributed to widespread use of screening mammography that detects early stage cancer, and advances in treatment. Mammograms occasionally detect precancerous conditions like ductal or lobular carcinoma-in-situ and atypical ductal or lobular hyperplasia, thus affording an opportunity to prevent the potential development of breast cancer in future. In 2009, USPSTF recommended biennial screening mammography for all women between the ages of 50 and 74.  This was an update from their prior recommendation in 2003 when annual screening mammography was recommended for all women between the ages of 40 and 74. 
These recommendations were based on a systematic review of eight randomized, controlled clinical trials across the world with breast cancer mortality outcomes for screening effectiveness. Breast cancer mortality results from these trials were used to estimate pooled relative risk. This review revealed that there is convincing evidence that screening with mammography reduces breast cancer mortality with greater absolute risk reduction for women aged 50-74 years, with the most benefit seen in women aged 60-69 years. Evidence for screening with mammography is lacking in women older than 75 years. In women aged 40-49 years, the task force found that there was moderate certainty that the net benefit of screening mammography was small and that there were considerable harms of screening like false positives, unnecessary further imaging and/or procedures, and psychological harms. This was the rationale behind their update in 2009.
The USPSTF also found that there was adequate evidence that teaching women self-breast examinations (SBEs) does not reduce mortality from cancer and thus recommends against this service. The benefits of clinical breast examination (CBE), magnetic resonance imaging (MRI) of the breast or digital (as compared with film) mammography in screening for breast cancer are also insufficient and USPSTF does not recommend the use of any of these services. In high risk women with strong family history of breast and ovarian cancers, a combined approach with mammogram and breast MRI has been advocated for screening and surveillance.
Cervical cancer is the third most common cancer in women worldwide with 500,000 new cases and 250,000 deaths annually.  A total of 80% of these cases are diagnosed in developing countries. Additionally, 99% of these cases are due to human papilloma virus (HPV) infection. An estimated 12,200 new cases of cervical cancer and 4210 deaths occurred in USA in 2010.  Deaths from cervical cancer in USA have decreased dramatically in the past few decades due to widespread implementation of screening tests including cytology (Papanicolau or Pap smear More Details) and HPV testing, thus making this service one of the biggest successes of public health. Most cases of cervical cancer are found in women who have not received adequate screening, either never screened or not screened in the past 5 years. There is a distinct opportunity for healthcare providers to ensure that more women be screened regularly.
The USPSTF recommended in 2012 that all women between the ages of 21 and 65 regardless of sexual history be screened with cytology every 3 years or in women 30-65 with cytology and HPV testing every 5 years.  These recommendations were based on a targeted systematic review of evidence including multiple observational studies, population-based studies, cross sectional studies, and randomized controlled clinical trials as well as modeling studies. This was an update from their prior statement in 2003 that recommended more frequent and earlier screening. A review of recent studies found no direct evidence that annual screening achieves better outcomes than screening every 3 years. Also, since cervical cancer is rare in women aged less than 20 years and HPV infections mostly clear spontaneously in teenage girls, the recent update recommended screening starting at age 21. The task force recommended no screening for women aged over 65 who have had appropriate screening in the past and are not at high risk for cervical cancer as well as for women who have had a hysterectomy with removal of cervix for a benign disease.
In its 2012 update, the USPSTF reviewed new studies including two randomized controlled trials comparing liquid based cytology to conventional pap smears and found no clinically meaningful difference in the rates of detection of precancerous cells between the two, though liquid-based cytology had less unsatisfactory specimens.  On the basis of several observational diagnostic accuracy studies they found that one time HPV screening was more sensitive than cytology but less specific for detecting cervical intraepithelial neoplasia and on the basis of two randomized controlled trials it was found that primary HPV screening detected more cases of CIN3 or cancer in women older than 30 years. In women younger than 30 years, there is a higher prevalence of HPV infection so false positive rates are also higher, though incidence of cervical cancer is lower.
Colorectal cancer is the third most common cancer among men and women and the second leading overall cause of cancer deaths in USA. The projected estimate in 2012 was 103,170 new cases of colon cancer and 40,290 new cases of rectal cancer with 51,690 deaths from both.  Majority of colon cancers start in a tubular adenoma and progress into a carcinoma. There is fair evidence that screening for colorectal cancer detects adenomatous polyps and early stage cancer and reduces cancer-related mortality in adults aged 50-75 years. It has been estimated that if goals for population screening for colorectal cancer could be achieved, 18,800 lives per year could be saved.  The three widely used methods of screening include fecal occult blood testing (FOBT), sigmoidoscopy, and colonoscopy.
In 2008, the USPSTF recommended screening for colorectal cancer using high sensitivity FOBT annually, sigmoidoscopy every 5 years with FOBT every 3 years, or colonoscopy every 10 years in all adults aged 50-75 years. This was based on evidence from multiple randomized controlled trials, diagnostic accuracy studies and other supporting evidence. Data suggested better detection of colorectal cancer and large adenomas with 2-3 days of sample collection for FOBTs than with 1 day of sample collection. Newer tests like fecal immunological test (FIT) have a higher sensitivity and specificity than FOBT and are now being used with increasing frequency for screening.
Prostate cancer is the most common cancer in men after skin cancer and the second leading cause of cancer deaths in the country. American Cancer Society estimated that there will be a total of 241,740 new cases of prostate cancer and 28,170 deaths in 2012 in USA.  It is a disease of older men and rare before 40. Majority of prostate cancer cases have a good prognosis even with watchful waiting only.  However, some cases are aggressive. Prostate specific antigen (PSA)-based blood test, with or without digital rectal examination or ultrasonography, has been used to screen men aged over 40 years for prostate cancer in USA without any strong evidence that screening reduces mortality from prostate cancer. PSA can detect asymptomatic prostate cancer. There is convincing evidence that many of these asymptomatic cancers will not grow or may grow so slowly that they will remain asymptomatic for the entire lifetime.  Therefore, screening with PSA may result in over-diagnosis and over-treatment of cancers that may not have progressed. Screening with PSA has remained controversial but still used frequently in primary care practices all across the country.
The recommendations of the USPSTF in 2008 were based on insufficient evidence at that time regarding PSA-based screening tests. Since then several randomized controlled trials in USA and Europe have been published and that data formed the rationale behind their 2012 recommendations against PSA-based screening for prostate cancer with convincing new evidence that PSA-based screening may have more harms than benefits. The two major trials that were reviewed by the USPSTF were the Prostate Lung Colorectal and Ovarian Cancer trial in US  as well as the European Randomized Study of Screening for Prostate Cancer.  While the American study did not show any reduction of mortality from screening with PSA, the European study showed a modest reduction. However, both studies concluded that there were significant harms related to screening with PSA including high false positives, complications from biopsy like bleeding and infection, negative psychological effects and persistent worry about cancer, additional testing including biopsy, over-diagnosis and over-treatment of screen detected cancers, and complications from treatment of low-grade tumors like impotence and urinary incontinence.
Cancer has been termed as the "emperor of all maladies" by Dr Siddhartha Mukherjee, an Oncologist in Columbia University Medical Center in New York.  It is one of the leading causes of death worldwide. Data from the International Agency for Research on Cancer (IARC) reveals that in 2008 there were 12.7 million new cancer cases globally and 7.6 million cancer deaths, with 56% of new cancer cases and 63% of the cancer deaths occurring in the less developed regions of the world.  The prevalence of cancer is expected to reach 20 million by 2030.  It is evident from the existing data that screening for cancer saves lives and decreases morbidity. Cancer prevention and early detection fall into the categories of primary and secondary prevention, respectively. In USA, it is routinely practiced by healthcare professionals based on guidelines from peer institutions like USPSTF. Similar evidence-based clinical practice guidelines exist in other Western countries like Canada and United Kingdom. However, screening for cancer is not widely practiced in the developing world including India in spite of high prevalence of the disease.
In a study published in the Lancet regarding cancer mortality in India, it was noted that cancer is an important cause of mortality in India with a staggering 70% of deaths due to cancer occurring in people aged between 30 and 69.  This was the first nationally representative published estimate of the prevalence of cancer morbidity and mortality in India and described tobacco-related cancers (oral and lung) and cervical cancer to be the most common types of cancers. Indirect estimates concluded that there were 950,000 new cases and 635,000 deaths from cancer in India in 2008, approximately 6% of all deaths. , Numbers were expected to rise due to various reasons and the diverse cultures, variations in lifestyle, challenges associated with collection of specific information about cancer prevalence and mortality, as well as unclear determinants of disease risk were identified as significant factors in future cancer-related research. The study concluded that prevention and early detection of tobacco related and cervical cancers would reduce cancer deaths in India, especially in the rural underserved areas.
In a developing country like India, the widespread practice of preventive healthcare could prove to be a cost effective strategy over time. Screening, prevention, early detection, and treatment of cancer would not only save more lives but also reduce healthcare costs from loss of productivity and expenses associated with treatment of advanced cancer. However, there remain several barriers toward such a target including scarce resources and the lack of an overarching public health policy, which make it nearly impossible to consider age-based cancer screening in current times. The guidelines suitable to Americans may not be so for the Indian population due to racial, ethnic, and behavioral differences.
Preventive healthcare for other common diseases like heart diseases, stroke, and diabetes have recently garnered interest. A report from the Indian Council for Research on International Economic Relations (ICRIER) published in September 2007 made specific recommendations to the government of India and the corporate sector based on a study done on a few best performing companies and employees from the manufacturing and service sectors.  These include corporate tax breaks for providing preventive care, fiscal incentives, income tax exemptions, collaboration between different government bodies, regular physical examinations, therapeutic lifestyle changes, etc. Small steps like these, if successful, may eventually lead to more research, evidence-based guidelines, and policies related to cancer screening too.
There are many aspects of current cancer screening in India. The government of India launched the National Cancer Control Program in 1975 to control the problem of cancer and revised its strategies in 1984-85 to focus on primary prevention and early detection. According to the National Cancer Control Program, two-thirds of cancers in India present in advanced and often incurable stages.  However, there are no formal screening guidelines for the common cancers. Public policy for age-specific screening would require research driven population-based scientific evidence. Access to care is a critical component of screening and lack of it would seriously impact any effort. Geographical and genetic differences in the prevalence of cancer should drive efforts to focus on reaching the target population and identification of high risk populations for certain cancers may be a feasible option to recommend screening.
The most appropriate choice of screening methods will need a profound understanding of the psychosocial and varied cultural factors that govern the intricate Indian society. Emphasis on effective education, practical solutions, and cost benefit analyses would need to be an integral part of future research in a multidisciplinary approach. Mass education for optimal utilization of available resources via media and community health programs to create awareness would be vital. Mobile cancer screening programs and multi-component tobacco cessation service programs with individual and group behavioral therapy inbuilt within workplace settings have proven to be acceptable and feasible and may need to be encouraged on a larger scale. ,, Since cytology-based cervical cancer screening is expensive and needs technical manpower, other cost effective screening methods like visual inspection may need to be implemented widely. Visual inspection after application of acetic acid (VIA) and visual inspection after application of Lugol's iodine (VILI) have been proven to be effective screening modalities in India and are simple, less expensive, provide immediate results, and do not need qualified manpower.  Then there remains the fact that screening will increase the number of cases detected and thus treatment demands will add another dimension to healthcare that would need to be addressed meticulously.
Clinical vignette- next steps
The woman in the clinical vignette would be offered a PAP smear, screening mammogram, and colon cancer screening of her choice (FOBT, sigmoidoscopy, or colonoscopy) in the United States.