APPENDIX B
Screening for Skin Cancer

Mark Helfand, M.D., M.P.H.,* Susan Mahon, M.P.H., and Karen Eden, Ph.D.

INTRODUCTION

In the United States in 1999, approximately one million new cases of basal cell and squamous cell carcinoma, and about 44,000 new cases of malignant melanoma, are expected to be diagnosed.1 Malignant melanoma is often lethal, and its incidence in the United States has increased rapidly over the past two decades. Nonmelanoma skin cancer is seldom lethal but, if advanced, can cause severe disfigurement and morbidity.

Advanced melanoma and invasive squamous cell carcinoma of the skin occur most often in the elderly, especially elderly men. Early detection and treatment of melanoma might reduce mortality, while early detection and treatment of squamous cell carcinoma and basal cell carcinoma might prevent major disfigurement, reduce the need for expensive reconstructive surgery, and to a lesser extent, prevent mortality.

In this paper, we examine published data on the effectiveness of screening for skin cancer by a physician. Specifically, we examine the accuracy of the tests used for screening, the diagnostic yield of screening in the general population, and evidence that treatment of cancers found by screening improves outcomes.

We use the term “screening” to denote a systematic effort to detect unsuspected disease by performing a total-body skin examination or by assessing the risk for skin cancer in all patients seen in the primary care setting. We did not

This evidence review was developed for the Institute of Medicine and the U.S. Preventive Services Task Force and was reviewed and approved by both groups. This paper may differ slightly in format from the version that will be released by the Task Force (expected early in 2000).

*  

Assistant Professors (Helfand and Eden) and Research Assistant (Mahon), Oregon Health Sciences University, Division of Medical Informatics/Outcomes.



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Extending Medicare Coverage for Preventive and Other Services APPENDIX B Screening for Skin Cancer Mark Helfand, M.D., M.P.H.,* Susan Mahon, M.P.H., and Karen Eden, Ph.D. INTRODUCTION In the United States in 1999, approximately one million new cases of basal cell and squamous cell carcinoma, and about 44,000 new cases of malignant melanoma, are expected to be diagnosed.1 Malignant melanoma is often lethal, and its incidence in the United States has increased rapidly over the past two decades. Nonmelanoma skin cancer is seldom lethal but, if advanced, can cause severe disfigurement and morbidity. Advanced melanoma and invasive squamous cell carcinoma of the skin occur most often in the elderly, especially elderly men. Early detection and treatment of melanoma might reduce mortality, while early detection and treatment of squamous cell carcinoma and basal cell carcinoma might prevent major disfigurement, reduce the need for expensive reconstructive surgery, and to a lesser extent, prevent mortality. In this paper, we examine published data on the effectiveness of screening for skin cancer by a physician. Specifically, we examine the accuracy of the tests used for screening, the diagnostic yield of screening in the general population, and evidence that treatment of cancers found by screening improves outcomes. We use the term “screening” to denote a systematic effort to detect unsuspected disease by performing a total-body skin examination or by assessing the risk for skin cancer in all patients seen in the primary care setting. We did not This evidence review was developed for the Institute of Medicine and the U.S. Preventive Services Task Force and was reviewed and approved by both groups. This paper may differ slightly in format from the version that will be released by the Task Force (expected early in 2000). *   Assistant Professors (Helfand and Eden) and Research Assistant (Mahon), Oregon Health Sciences University, Division of Medical Informatics/Outcomes.

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Extending Medicare Coverage for Preventive and Other Services examine the effect of skin surveillance on children or on patients with familial syndromes that confer a high risk of melanoma. We also did not examine the value of routine diagnosis and treatment of skin cancer in clinical practice. In everyday primary care, the clinician sees the skin of every patient’s face and, in many, the extremities, chest, and back. Clinicians almost universally agree that incidental discovery of a suspicious skin lesion should prompt an evaluation, including a skin biopsy and a thorough inspection of the skin. The data we reviewed about screening do not address the value of attention to the skin as part of conscientious clinical care. Other strategies to prevent skin cancer, such as promotion and counseling to reduce risky health behaviors and skin self-examination, are not addressed in this review. However, many studies combine screening with health promotion programs, and screening may itself contribute to primary prevention, since it provides the physician with an opportunity to increase awareness of skin cancer and to demonstrate examination techniques that patients can apply themselves. EPIDEMIOLOGY AND BURDEN OF SUFFERING Melanoma In the United States, the lifetime risk of being diagnosed with melanoma is 1.74 percent in white men and 1.28 percent in white women. The lifetime risk of dying of melanoma is 0.36 percent in men and 0.21 percent in women. Between 1973 and 1995, the incidence of melanoma in the United States increased about 4 percent per year, from 5.7 per 100,000 in 1973 to 13.3 per 100,000 in 1995, according to data from the Surveillance, Epidemiology, and End Results program (SEER) of the National Cancer Institute.2 By comparison, the overall rate in Queensland, Australia is 55 per 100,000. The elderly and, in particular, elderly men bear a disproportionate burden of morbidity and mortality from melanoma. As shown in Figure B-1, older men have the highest incidence of invasive melanoma. In 1995, the age-adjusted incidence rate was 68.7 per 100,000 in white men over age 65 and 30.6 per 100,000 in white women over 65. Men over 65 years of age, who constitute 5.2 percent of the U.S. population, have 22 percent of newly diagnosed malignant melanomas each year; women over 65 who constitute 7.4 percent of the population, have 14 percent. Melanoma in the elderly is not only more common, but also more lethal than in younger populations. In Australia, where for many years public education about melanoma has been intense, 75 percent of “thick” (>3 mm) melanoma lesions and 75 percent of deaths occur in people over 50 years of age; 50 percent of deaths occur in men over 50.3 Similarly, in the United States, about 50 percent of deaths from melanoma are in men over 50 years of age.2 Figure B-2

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Extending Medicare Coverage for Preventive and Other Services FIGURE B-1 Melanoma age-specific incidence and mortality. shows that melanoma in the elderly, particularly elderly men, is more likely to be detected in advanced stages. For men in their 40s, for example, there are six times as many cancers diagnosed as deaths; for men in their 70s, there are about four cancers diagnosed per death. Some experts argue that the elderly, particularly elderly men, may have lower “skin awareness” and lower rates of skin self-examination, resulting in higher rates of advanced melanoma.4 Overall mortality from melanoma has increased. Between 1973 and 1995, overall mortality rates for melanoma increased by 1.3 percent per year, from 1.6 per 100,000 in 1973 to 2.2 per 100,000 in 1995. Nearly all of the increase was in white men (2.2 to 3.6 percent), especially older white men. Five-year survival for melanoma has improved to 88 percent currently from 80 percent 20 years ago. During this time, the rate of diagnosis of “early” or thin melanoma increased sharply, but so did the incidence of thicker (>3 mm) melanomas.5 Changes over time in ascertainment, diagnostic criteria, self-examination, and registry procedures make it difficult to draw reliable inferences about the effectiveness of early detection from epidemiologic data.5–7 In an analysis of trends in Australia and New Zealand, Burton and colleagues noted that although there has been a huge increase in the incidence of very thin melanomas, the incidence of thick melanomas has increased as well.8 Some experts interpret this to mean that increased surveillance in the population may detect a relatively unaggressive, unimportant type of thin melanoma.7–10 Increased detection of these very thin, nonmetastasizing melanomas would increase the incidence and five-year survival rates for melanoma but would have little impact on mortality. However, in contrast to prostate and thyroid cancers, in which a large

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Extending Medicare Coverage for Preventive and Other Services FIGURE B-2 Ratio of incidence to mortality by age. reservoir of unaggressive cancers are known to exist, longitudinal studies of melanoma have not established the frequency or existence of histologically malignant, but behaviorally benign, melanoma in the general population. Nonmelanoma Skin Cancer Rates of nonmelanoma skin cancer in the United States are difficult to determine, since these cancers are not typically tracked by cancer registries. Cancer registries in Denmark and Canada do include nonmelanoma skin cancers. In British Columbia, Canada, the age-standardized incidence rate for basal cell cancer in men was 70.7 per 100,000 in 1973, increasing to 120.4 per 100,000 in 1987.11 In women, basal cell cancer incidence increased from 61.5 to 92.2 per 100,000 over the same period. Squamous cell cancer incidence rose from 16.6 to 31.2 per 100,000 in men and from 9.4 to 16.9 per 100,000 in women. Population-based surveys show substantial variation among geographic areas. In Queensland, Australia in the early 1990s, the age-adjusted incidence rates of basal cell carcinoma among men and women were 2,074 and 1,579 per 100,000 per year, respectively.12 Squamous cell carcinoma occurred at half the rate of basal cell carcinoma among men and at about one-third the rate among women. In Geraldton, Western Australia, the estimated incidence of basal cell carcinoma was 1,335 per 100,000 in men and 817 per 100,000 in women.13 In that community, the prevalence of nonmelanoma skin cancer in men and women

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Extending Medicare Coverage for Preventive and Other Services under 65 years of age was 7 percent in men and 4.7 percent in women; approximately 90 percent of these were basal cell cancers. A survey of one large health plan in Albuquerque, New Mexico, which was not population based, found age-standardized basal cell cancer rates of 1,073 per 100,000 in non-Hispanic white men and 415 per 100,000 in non-Hispanic white women. Squamous cell cancer rates were 214 and 50 per 100,000 for non-Hispanic white men and women, respectively. Rates are much lower in other U.S. studies. A population-based study in Rochester, Minnesota, covering the years 1976–1984 found that age-standardized incidence rates per year of basal cell cancer were 175 per 100,000 in men and 124 per 100,000 in women.14,15 Rates of squamous cell cancer were 63.1 per 100,000 in men and 22.5 per 100,000 in women. Rates of both basal cell cancer and squamous cell cancer increased with advancing age. A population-based study of NMSC in New Hampshire suggests that incidence rates are increasing. This study looked at incidence rates for two time periods, 1979–1980 and 1993–1994.16 In men, the age-adjusted incidence of basal cell cancer increased from 170 per 100,000 in 1979–1980 to 310 per 100,000 in 1993–1994; and in women basal cell cancer incidence rose from 91 to 166 per 100,000 over the same period. For squamous cell cancer, incidence rates in men rose from 29 to 97 per 100,000 over these periods, and in women, squamous cell cancer incidence rose from 7 to 32 per 100,000. NATURAL HISTORY, DIAGNOSIS, AND STAGING OF SKIN CANCER Melanoma There are four major subtypes of melanoma: superficial spreading, nodular, lentigo maligna melanoma, and acral lentiginous melanoma.17 Superficial spreading melanoma, the most common subtype in whites, is usually diagnosed at an early (thin) stage before there is a high risk of metastasis. Nodular melanoma is the second most common subtype in whites. Nodular melanomas are difficult for patients to find and are usually diagnosed in a more advanced stage.18 The natural history of nodular melanoma is controversial.19 The prevailing view is that nodular melanoma is characterized by rapid, early vertical growth and lack of an identifiable radial growth phase. To determine which skin lesions are suspicious for melanoma, some clinicians in the United States use the ABCD checklist for detecting melanoma.20 With this system, pigmented lesions are classified as suspicious for melanoma if they have an asymmetric shape; an irregular border that is scalloped, uneven, or ragged; varied color; or a diameter larger than 6 mm. Some add a fifth criterion (ABCDE) for elevation or enlargement. Some clinicians in the United Kingdom use a seven-point checklist that includes change in mole size, shape,

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Extending Medicare Coverage for Preventive and Other Services and color; crusting or bleeding; sensory change; and a mole greater than 7 mm in diameter.20 Once a lesion suspected to be cancer is identified, one of several biopsy techniques is employed to obtain tissue for analysis. The pathological diagnosis of suspicious pigmented lesions can be difficult, especially for borderline and in situ neoplasms. In one recent study, four histopathologists evaluated 140 slides and classified each lesion as “melanoma” or “other pigmented lesion”; they were in agreement on diagnoses for 74 percent (kappa=.61) of the slides.21 Similarly, when eight expert pathologists (recruited based on publications and reputations) classified 37 slides as “benign,” “malignant,” or “indeterminate,” they had complete agreement, or only one discordant, on 62 percent (kappa= .50) of the cases.22 Stage is the most important prognostic factor in melanoma. The American Joint Commission on Cancer Classification, which is based on the TNM (tumor, node, metastasis) system, describes the stages from I to IV. Stage I is a primary tumor less than 1.5 mm in thickness with no regional lymph node metastases; Stage II is a primary tumor 1.5–4.0 mm in thickness with no regional lymph node metastases; Stage III is any primary tumor with regional lymph node metastases or in-transit metastases; and Stage IV is any primary tumor with distant metastases.23 According to SEER data through 1995, five-year relative survival rates for localized, regional, and distant disease were 96 percent, 59 percent, and 12 percent, respectively.2 The thickness of the primary tumor is the strongest predictor of prognosis. To measure thickness of a melanoma, the pathologist uses a device called a “micrometer,” similar to a small ruler under the microscope. This technique is called the Breslow measurement.24 In general, melanomas less than 1 mm in depth have a very small chance of metastasizing. Five-year survival for those with melanomas between 1.5 mm and 4 mm is approximately 70 percent, and for those with melanomas thicker than 4 mm, it is about 45 percent. Thickness of the melanoma also guides the choice of therapy. Nonmelanoma Skin Cancers Basal cell carcinoma and squamous cell carcinoma are the most common forms of skin cancer. Despite their very high incidence they account for less than 0.1 percent of cancer deaths. There are several morphological types of basal cell cancer, such as nodular, ulcerative, and plaque-like but regardless of type, metastasis is very rare. Basal cell carcinoma can be locally destructive and frequently recurs. Squamous cell cancers usually occur on chronically sun-exposed areas of the skin, especially the face, ears, or backs of the hands. Squamous cell cancer has the potential to metastasize and may account for up to 20 percent of deaths

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Extending Medicare Coverage for Preventive and Other Services from skin cancer. A large primary tumor (>2 cm) is associated with an increased risk of metastasis. Most studies of the natural history of nonmelanoma skin cancer have been done in selected patients who have an elevated risk due to environmental exposures, such as Psorolen plus ultraviolet-A (UV-A) radiation for psoriasis.25,26 Patients with these exposures may constitute a substantial proportion of all patients who die of metastatic squamous cell cancer.27 Very elderly men are also overrepresented among patients who die of squamous cell cancer. While there is strong suspicion on clinical grounds that advanced locally invasive or metastatic nonmelanoma skin cancers result from medical neglect, careful studies of the rate of progress of nonmelanoma skin cancers in the elderly are lacking. RECOMMENDATIONS OF SECOND TASK FORCE AND OTHERS Current recommendations of professional societies regarding screening for skin cancer vary. The American Cancer Society recommends skin examination every three years for people between 20 and 40 years of age and yearly for anyone over 40. The American College of Preventive Medicine and the U.S. Preventive Services Task Force28 recommend total body skin examination in high-risk individuals who see a physician for other reasons, but they do not recommend routine screening. All of these organizations advise some form of public or patient education to change behaviors that may increase the risk of skin cancer and increase the likelihood of early self-detection. ANALYTIC FRAMEWORK AND KEY QUESTIONS Before the consequences of screening can be estimated, a necessary first step is to formulate the screening problem by specifying the population that screening is intended to reach; the screening tests, follow-up tests, and treatments that will be used; and the types of outcomes that will be affected by screening. The analytic framework in Figure B-3 shows the interventions, intermediate outcome measures, and health outcome measures we examined. The accompanying key questions (Figure B-4) correspond to the numbered arrows in the analytic framework and articulate the main questions that guided our literature review and that are addressed in the results section of this appendix. We studied screening in the general adult population and in the elderly, the group with the highest prevalence of and mortality from skin cancer. We have included studies of both mass-screening and case-finding programs to detect and treat melanoma and nonmelanoma skin cancer in the general population. In mass-screening programs, self-selected individuals respond to an invitation to undergo a total-body skin examination. Those with suspicious skin lesions are

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Extending Medicare Coverage for Preventive and Other Services FIGURE B-3 Screening for skin cancer: Analytic framework.

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Extending Medicare Coverage for Preventive and Other Services Accuracy of Screening Arrow 1a How accurate is total-body skin examination in the detection of cancer? How accurate are risk-assessment tools as a screening test for skin cancer? Consequences of Screening Arrow 1b How often does screening detect suspicious lesions? How often does screening result in a diagnosis of melanoma? How often does screening result in a diagnosis of nonmelanoma skin cancer? How often does screening lead to referral for follow-up and biopsy? How do characteristics of the screening program affect the yield of screening? Compared to usual care, how much earlier does screening detect skin cancers and precancerous lesions? Arrow 1c What is the effect of screening on patients’ skin knowledge and self-care behavior? Arrow 2 What are the adverse effects of screening? Arrow 3 Is there direct evidence that screening for skin cancers leads to reduced morbidity and mortality? Effectiveness of Early Treatment Arrow 4a Does treatment of non-melanoma skin cancer found by screening reduce morbidity and mortality? Arrow 4b Does treatment of malignant melanoma found by screening reduce morbidity and mortality? FIGURE B-4 Key questions.

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Extending Medicare Coverage for Preventive and Other Services referred to their primary care physician or to a specialist for further evaluation. In case-finding programs, a total-body skin examination is offered to individuals who see a primary care physician for other reasons. A total-body skin examination may be offered to every individual or to selected individuals considered at high risk of skin cancer. Because the great majority of Medicare beneficiaries do see a physician each year, case-finding in physicians’ offices might reach high-risk patients, especially elderly men, who are less likely than other groups to respond to an invitation to be screened in a mass screening program. We sought studies of the accuracy of two methods of screening for skin cancer (Arrow 1a): (1) performing a total-body skin examination in all patients seen in the primary care setting, and (2) assessing the risk for skin cancer in all patients, followed by a total-body skin examination in those found to be at high risk. The primary aim of these strategies is earlier detection of melanoma, for which an examination confined to areas not covered by clothing is likely to miss a high proportion of potentially lethal cancers.29 To assess the accuracy of these methods, both for melanoma and for nonmelanoma skin cancer, we sought studies that used these initial tests to screen in the general population or in the elderly and then confirmed positive screening test results with skin biopsy results. We examined the consequences of screening on detection of squamous cell carcinoma, basal cell carcinoma, and malignant melanoma (Arrow 1b). Specifically, we examined how often patients are found to have skin cancer, how often suspected skin cancer is confirmed by biopsy, and at what stage cancer is found. In addition to early detection, screening itself might confer a potential benefit by improving patients’ knowledge and self-examination skills. We therefore sought evidence about the effect of screening on patients’ health beliefs and practices regarding skin cancer prevention (Arrow 1c). We also considered the adverse effects of screening, including the frequency and consequences of false positive examinations or biopsies and the diagnosis of noncancerous lesions that may not require treatment (Arrow 2). In considering outcomes, we sought, but did not find, direct evidence from controlled studies of the effect of screening on health outcomes (Arrow 3, dotted line) such as mortality and quality of life. In the absence of randomized trials of screening, these links may be made by studies of the association between delay of diagnosis and the outcome of cancer or of the outcomes of screened versus nonscreened populations. Note that we did not examine the effectiveness or adverse consequences of various treatments for skin cancer, but rather investigated the evidence that detection of earlier cancers by screening in the general population is associated with reduced mortality and morbidity.

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Extending Medicare Coverage for Preventive and Other Services METHODS Literature Review To find relevant articles on screening for skin cancer, we searched the MEDLINE database for papers published in 1994 or later, using the search string in Addendum B-1 (see page 214). We conducted monthly updates during the course of the project. We included studies if they contained data on yield of screening, screening tests, risk factors, risk assessment, effectiveness of early detection, or cost-effectiveness. Two reviewers evaluated abstracts for inclusion. The reviewers also searched the reference lists of relevant reviews. Of 54 included studies, 5 contained data on accuracy of screening tests, 24 contained data on yield of screening, 8 contained data on stage or thickness of lesions found through screening, 11 addressed risk assessment, and 7 addressed the effectiveness of early detection (some studies addressed more than one topic) (see Addendum B-2, page 215). We retrieved the full text of these articles and abstracted the data as described below. In addition, we retrieved the full text of 47 studies of various risk factors for skin cancer. We read these articles but did not systematically abstract them. We identified the most important studies from before 1994 from the Guide to Clinical Preventive Services, Second Edition;28 from high-quality reviews published in 1994 and 1996;30,31 from reference lists of recent studies; and from experts. We found that many relevant publications from before 1994 were preliminary results of programs discussed in greater detail in more recent publications. Data Extraction and Synthesis We abstracted the following descriptive information from full-text, published studies of screening and recorded it in an electronic database: study type (mass screening, population based, case finding, other); setting (hospital, community, specialty clinic, primary care, other); population (percent white, age), recruitment (volunteers, invitation, random sampling), screening test (total-body skin examination, partial skin examination, lesion-specific examination, other); examiner (dermatologist, primary care physician, other); advertising targeted at high-risk groups or not targeted; reported risk factors of participants; and procedure for referring patients found to have a positive screen. We also abstracted the number and probability of the following events from each study: referrals for skin examination; compliance with referral; suspected basal cell cancers, squamous cell cancers, actinic keratoses, and melanoma; confirmed melanoma and melanoma in situ; negative screening examinations; biopsies performed; the number with confirmed melanoma and number with suspicious melanoma; and the number with confirmed melanoma and number of all

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Extending Medicare Coverage for Preventive and Other Services elderly is particularly important, because there is little evidence from empirical studies that lethal tumors in this group are detectable when they are still in a curable stage.

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Extending Medicare Coverage for Preventive and Other Services TABLE B-4 Summary of Evidence for Screening for Skin Cancer Linkage in Analytic Framework Evidence Code Quality of Evidence 1a. Accuracy of total body skin examination: evidence that total body skin examination can detect skin cancer. II-2 Fair: The accuracy of a total body skin examination by primary care physicians in unselected patients may be low. Reliability of pathologic diagnosis in community practice in the U.S. is not clear. 1b. Accuracy of risk-assessment: evidence that a questionnaire or interview, followed by exam in selected patients, can detect skin cancer. II-2 Fair: Mole counts and other factors predict elevated risk over time, but no study has determined the accuracy of risk stratification followed by total body skin examination in selected patients as a screening method. 2. Adverse effects of screening: evidence that screening causes significant harms. III Poor: most postulated adverse effects have not been evaluated in studies. 3. Effectiveness of early detection: evidence that persons detected through screening have better outcomes than those who are not screened. II-3 Poor: There are no studies that directly link screening to lower mortality and morbidity. Most well-done population-based studies concern promotion of self-care behaviors such as self-examination rather than universal screening.

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Extending Medicare Coverage for Preventive and Other Services 4a. Effectiveness of treatment of nonmelanoma skin cancer found by screening. III Poor: The hypothesis that early detection by screening could reduce mortality and morbidity is plausible but has not been examined in studies. 4b. Effectiveness of treatment of melanoma found by screening. II-1, III Fair: There are no controlled studies of treatment in patients found by screening to have thin melanomas, but epidemiologic studies, studies of skin health behaviors, and studies of factors associated with advanced melanoma suggest that elderly men are at high risk and are unlikely to benefit from health promotion efforts.     Studies of delay in diagnosis have conflicting results, and the ability of screening to reach individuals at high risk and to find aggressive tumors while they are still curable have not been established. *I=randomized controlled trial; II-1=controlled trial without randomization; II-2=cohort or case-control analytic studies; II-3=multiple time series, dramatic uncontrolled experiments; II-1=controlled trial without randomization; II-2=cohort or case-control analytic studies; II-3=multiple time series, dramatic uncontrolled experiments; and III opinions of respected authorities, descriptive epidemiology.

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Extending Medicare Coverage for Preventive and Other Services ADDENDUM B-1 STRATEGY FOR SKIN CANCER SEARCH Skin neoplasms Exp mass screening genetic screening mass chest x-ray multiphasic screening vision screening mandatory screening Screen$.tw. (Text word taken from title and abstract of article) Exp physical examination self-examination skinfold thickness Exp neoplasms metastasis lymphatic metastasis neoplasm circulating cells neoplasm seeding neoplasms, unknown primary Neoplasm recurrence, local Recurrence Exp morbidity incidence prevalence Exp sensitivity and specificity predictive value of tests ROC curve 2 or 3 or 4 or 5 or 6 or 7 or 8 or 9 Skin neoplasms/mo (mortality) Skin neoplasms/ep (epidemiology) 10 or 11 or 12 1 and 13 Limit 14 to human Limit 15 to english language Looked at english abstracts for foreign language articles

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Extending Medicare Coverage for Preventive and Other Services ADDENDUM B-2 SCREENING FOR SKIN CANCER: INCLUSION CRITERIA FOR EVIDENCE TABLES

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Extending Medicare Coverage for Preventive and Other Services REFERENCES 1. Landis SH, Murray T, Bolden S, Wingo PA. Cancer statistics, 1999. CA Cancer Jr Clin. 1999; 49:8. 2. Ries LAG, Kosary CL, Hankey BF, Miller BA, Edwards BK. SEER Cancer Statistics Review, 1973–95. Bethesda, MD: National Cancer Institute, 1998. 3. Jelfs P, Coates M, Giles G. Cancer in Australia 1989–1990 (with projections to 1995). Canberra, Australian Institute of Health and Welfare; 1996. 4. Kelly J. Melanoma in the elderly—A neglected public health challenge. Med J Aust 1998; 169:403–404. 5. Dennis LK. Analysis of the melanoma epidemic, both apparent and real: data from the 1973 through 1994 surveillance, epidemiology, and end results program registry. Arch Dermatol, 1999; 135:275–280. 6. Berwick M, Halpern A. Melanoma epidemiology. Curr Opin Oncol. 1997; 9:178–182. 7. Swerlick RA, Chen S. The melanoma epidemic: More apparent than real? Mayo Clin Proc 1997; 72:559–564. 8. Burton R, Armstrong B. Recent incidence trends imply a nonmetastasizing form of invasive melanoma. Melanoma Res 1994; 4:107–113. 9. Swerlick RA, Chen S. The melanoma epidemic. Is increased surveillance the solution or the problem? Arch Dermatol 1996; 132:881–884. 10. Burton R. An analysis of a melanoma epidemic. Int J Cancer 1995; 55:765–770. 11. Gallagher RP, Hill GB, Bajdik CD, et al. Sunlight exposure, pigmentation factors, and risk of nonmelanocytic skin cancer. II. Squamous cell carcinoma. Arch Dermatol 1995; 131:164–169. 12. Green A, Battistutta D, Hart V, Leslie D, Weedon D. Skin cancer in a subtropical Australian population: Incidence and lack of association with occupation. The Nambour Study Group. Am J Epidemiol 1996; 144:1034–1040. 13. Kricker A, English DR, Randell PL, et al. Skin cancer in Geraldton, Western Australia: A survey of incidence and prevalence. Med J Aust 1990; 152:399–407. 14. Chuang TY, Popescu A, Su WP, Chute CG. Basal cell carcinoma. A population-based incidence study in Rochester, Minnesota. J Am Acad Dermatol 1990; 22:413–417. 15. Chuang TY, Popescu NA, Su WP, Chute CG. Squamous cell carcinoma. A population-based incidence study in Rochester, Minnesota. Arch Dermatol 1990; 126:185–188. 16. Karagas MR, Greenberg ER, Spencer SK, Stukel TA, Mott LA. Increase in incidence rates of basal cell and squamous cell skin cancer in New Hampshire, USA. New Hampshire Skin Cancer Study Group. Int J Cancer 1999; 81:555–559. 17. McGovern V, Cochran A, Van der Esch E. The classification of malignant melanoma, its histological reporting and registration: Revision of the 1972 Syndey classification. Pathology 1986; 18:12–21. 18. Hersey P, Sillar RW, Howe CG, et al. Factors related to the presentation of patients with thick primary melanomas. Med J Aust 1991; 154:583–587. 19. Heenan PJ, Yu L, English DR. Melanoma in the elderly—A neglected public health challenge [letter]. Med J Aust 1999; 170:394–395.

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