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Nonmelanoma Skin Cancer Mortality (1988-2000)
The Rhode Island Follow-Back Study
Kevan G. Lewis, MS;
Martin A. Weinstock, MD, PhD
Arch Dermatol. 2004;140:837-842.
ABSTRACT
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Objectives To estimate (1) the magnitude of and the components and factors associated with nonmelanoma skin cancer (NMSC) mortality and (2) the proportion of deaths misclassified as NMSC.
Design Population-based follow-back study.
Setting and Patients All Rhode Island residents whose deaths between 1988 and 2000 were attributed to NMSC.
Main Outcome Measures Distribution of diagnoses, verification of the causes of death, and characterization of associated factors.
Results The proportion of misclassified deaths was significantly higher for nongenital NMSC (57%) than for genital NMSC (18%; P<.001). Most of the deaths misclassified as nongenital NMSC were caused by squamous cell carcinoma of mucosal surfaces. The age-adjusted NMSC mortality rate was 0.91 (per 100 000 persons per year), of which almost half (0.45) were due to genital carcinoma. Nonmelanoma skin cancer mortality increased sharply with age. The mortality rate from nongenital NMSC in men was more than twice that in women, but for genital NMSC this ratio was reversed. Skin cancers originating on the ear were responsible for more than a quarter of all deaths caused by nongenital NMSC. No cases of NMSC mortality occurred in organ transplant recipients. Many individuals had comorbid psychiatric conditions or evidence of unreasonable delay in seeking medical care for their lesions.
Conclusions Misclassifying the cause of death as nongenital NMSC accounts for a large source of error on death certificates in Rhode Island. Overall, nongenital squamous cell carcinoma and basal cell carcinoma death rates have declined, and mortality due to genital carcinoma was about half of total NMSC deaths. The dermatology community should emphasize prevention of mortality from genital skin cancer, while continuing to stress the importance of reducing excessive exposure to UV light and prompt treatment of NMSC.
INTRODUCTION
Nonmelanoma skin cancer (NMSC) is the most commonly diagnosed malignancy in the United States, and recent reports suggest that the incidence is increasing.1-2 Despite the magnitude of the public health burden, investigation of NMSC mortality has been limited.3 Mortality due to NMSC in Rhode Island may be related to several factors including rising incidence, increased awareness leading to earlier detection, aging of the population, the introduction of Mohs surgery in 1989, possible changes in the accuracy of death certificate coding, and potentially greater scrutiny by the medical community leading to better treatment. In addition, the number of organ transplant recipients in Rhode Island has increased over the last decade; the risk of NMSC mortality in this subgroup is higher than in the general population. The purpose of this study was to determine the rate of NMSC mortality among Rhode Island residents from 1988 through 2000 and to identify circumstances that may have contributed to a fatal outcome. We also examined the occurrence of coding errors in cause-of-death certification under the International Classification of Diseases, Ninth (ICD-9) and 10th (ICD-10) Revision, and compared these results with those from a previous study concerning the period from 1979 through 1987. Whereas mortality from carcinomas arising on genital skin were excluded from the prior investigation, deaths attributed to this cause are included herein. Results of this investigation may be useful in developing strategies to reduce mortality from NMSC.
METHODS
Medical records (death certificates, Rhode Island Department of Health cancer registry data, and hospital medical records) were sought for all Rhode Island residents whose deaths from 1988 to 2000 were attributed to NMSC. Death certificates for which the cause of death was attributed to NMSC under ICD-9 and ICD-10 rubrics were obtained from the Rhode Island Department of Health. Carcinomas of genital skin (ie, vulva, penis, and scrotum) were included, but cutaneous lymphomas (ICD-9 202.1 and 202.2 and ICD-10 C84.0 and C84.1) and cancers of the perianal skin (ICD-9 154.3 and ICD-10 C21.0) were excluded. Institutional review board approval was obtained from the Rhode Island Department of Health as well as from Kent, Memorial, Miriam, Newport, Rhode Island, Roger Williams, South County, St Joseph's, and the Veterans Affairs Medical Center hospitals.
All 239 death certificates meeting these criteria were obtained. Complete medical records were available for 135 cases, incomplete records were available for 96 cases, and no records (except for the death certificate) were available for 8 cases. Records were incomplete or absent in some cases in which the diagnosis and treatment of disease occurred out of state or in an outpatient or nursing home setting or in cases in which the hospital records had been destroyed or could not be located by the medical records department staff.
In cases for which records were available, the cause of death was ascertained by documenting a histologic diagnosis of NMSC. In addition, the events immediately prior to death were reviewed to verify that the NMSC directly contributed to the fatal outcome. If the events leading to death were not well delineated, documentation of advanced disease such as invasion of the skull or orbital bones or unresectable metastases was considered evidence for a direct contribution to death. Cases in which the above information was available were categorized as "confirmed NMSC deaths." Cases were categorized as "probable NMSC deaths" when there was a diagnosis of invasive NMSC or suggestion that it was advanced and contributed to death in the absence of severe comorbid conditions but no specific information on the presence of metastatic disease nor events leading to death. Additional cases in which there was sufficiently detailed language on the death certificate to suggest that the cause of death was due to NMSC (eg, squamous cell carcinoma [SCC] of the ear) were also categorized as probable NMSC deaths.
Cases in which death was caused by a melanoma, noncutaneous malignancy, or a severe comorbidity were categorized as "misclassified deaths." The same parameters including documentation of metastasis, bony invasion, and events preceding death were applied to differentiate "confirmed misclassified deaths" from "probable misclassified deaths." Additional cases in which there was sufficiently detailed language on the death certificate to suggest that the cause of death was misclassified (eg, "squamous cell carcinoma" of the head and neck) in the absence of other information from the medical record were also categorized as probable misclassified deaths. Cases in which death appeared to result from the contribution of both NMSC and more severe comorbid conditions were categorized as "multifactorial deaths." Cases in which medical records were absent or devoid of useful information regarding NMSC and cause of death were categorized as "indeterminate deaths." In addition to the cause of death, data on patient demographics, risk factors for NMSC, the anatomic location and histologic features of the primary tumor, and the course of disease were abstracted.
For the purpose of examining the issue of misclassification, only confirmed (NMSC and misclassified) deaths were analyzed. For the purpose of calculating mortality rates, both confirmed and probable NMSC deaths were included in the analysis. Population estimates for Rhode Island were derived from the 1990 and 2000 Rhode Island Census. Mortality rates are age-adjusted to the 2000 US standard population (available at: http://seer.cancer.gov/stdpopulations/; accessed September 6, 2003) unless otherwise specified and are expressed as the number of deaths per 100 000 persons per year.
RESULTS
ACCURACY OF CAUSE OF DEATH CERTIFICATION
Results are based on 239 Rhode Island residents whose deaths between 1988 and 2000 were attributed to NMSC. Of these, 135 deaths (72 confirmed and 63 probable) were caused by NMSC. The remaining 104 deaths were misclassified (56 confirmed and 33 probable), multifactorial (7 deaths), or indeterminate (8 deaths). Hence, 44% of deaths with a confirmed cause (NMSC or misclassified) were, in fact, misclassified (Table 1). Among confirmed cases, misclassified deaths differed from NMSC deaths with respect to age at death (median, 66 vs 78 years; P = .01) and sex (54% vs 43% men; P = .02). An autopsy was performed in only 1 confirmed case. Although not included in the analysis of misclassification, 2 cases categorized as probable NMSC deaths were caused by SCC but were listed as basal cell carcinoma (BCC) on the death certificates. Deaths attributed to malignant neoplasms of the vagina (ICD-9 184.0) were not included in the analysis except for 1 death that was confirmed to be caused by NMSC of the vulva. Of the 72 confirmed NMSC deaths, 15 (21%) occurred in patients with physical and psychiatric disabilities that may have contributed to a fatal outcome, including anxiety or depression (7 cases), schizophrenia (2 cases), dementia (3 cases), blindness and/or deafness (2 cases), and morbid obesity (1 case).
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Table 1. Proportion of Deaths Misclassified as NMSC*
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Of 128 confirmed (NMSC and misclassified) deaths, 84 were attributed to nongenital NMSC; the remaining 44 deaths were attributed to vulvar (32 deaths) and penile carcinoma (12 deaths). Of these 84 deaths, 36 (43%) were correctly classified as nongenital NMSC and were caused by SCC (25 deaths), BCC (5 deaths), and other NMSC types (6 deaths). Analysis of misclassified cases revealed that 85% (41/48) were due to SCC arising from mucosal sites in the head and neck including larynx, pharynx, and oral cavity. These misclassified cases were typically described on death certificates as "squamous cell carcinoma of the head and neck" and were most commonly coded under ICD-9 rubric 173.4 (NMSC of the scalp and neck) (Table 2). The proportion of correctly classified deaths under ICD-9 173 (38% [26/68]) increased under the corresponding ICD-10 C44 (64% [9/14]), but this difference did not reach statistical significance (P = .10).
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Table 2. Proportion of Correctly Classified Cases Listed by Cause of Death*
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Of the 128 confirmed (NMSC and misclassified) deaths, 32 were attributed to vulvar carcinoma, of which 26 (81%) were correctly classified. Analysis of misclassified cases revealed that the cause of death was SCC of the vagina; adenocarcinoma of the cervix, uterus, or ovary; or other gynecological cancers. Twelve of the 128 deaths were attributed to penile carcinoma, of which 10 (83%) were correctly classified. The 2 misclassified deaths were caused by melanoma and ependymoma.
MORTALITY RATES AND FACTORS ASSOCIATED WITH MORTALITY
The overall NMSC mortality rate for Rhode Island residents for the period from 1988 through 2000 is estimated at 0.91 (0.99 in men and 0.86 in women) (Table 3).
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Table 3. Mortality Rates (No. of Deaths) for Nonmelanoma Skin Cancers*
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Nongenital SCC
Nongenital SCC was the cause of 44 (25 confirmed and 19 probable) deaths. The median age at death was 82 years (range, 34-96 years). Twenty-seven deaths (61%) occurred in men, and all deaths occurred in whites, who comprised 91% of the Rhode Island population in 1990. Metastases were documented in 16% of cases at the time the primary tumor was diagnosed and were documented at some point in the course of the malignancy in all but 23% of cases. Median survival from the time of initial diagnosis was 17 months. The Rhode Island nongenital SCC mortality rate is estimated at 0.29 (0.50 in men and 0.18 in women).
Primary lesions occurred most commonly on the skin of the head or neck including the ear (9 cases), face excluding the nose and eyelids (11 cases), lip (5 cases), and scalp (5 cases). Lesions originating on the extremities were documented in 14% (6/44) of cases. Most (86% [38/44]) of the deaths appeared to be related to sun exposure by virtue of their origin on sun-exposed skin (head, neck, back, chest, or extremities) and the lack of evidence for another cause. Histologically, 20% (9/44) were well differentiated, 32% (14/44) were moderately differentiated, and 34% (15/44) were poorly differentiated; detailed histological data were not available in 6 cases. We found chronic ulcers in 3 cases, chronic osteomyelitis in 1 case, prior exposure to therapeutic radiation in 2 cases, history of skin cancer in 4 cases, and/or other noncutaneous malignancies in 2 cases, but found no cases in organ transplant recipients. There was documentation of unreasonable delay in seeking medical treatment in 9 cases, of which 3 were found to have metastatic disease at the time of presentation.
Basal Cell Carcinoma
Twelve (5 confirmed and 7 probable) deaths were caused by BCC. The median age at death was 78 years (range, 61-103 years); the median ages for men and women were 65 and 83 years, respectively. Six deaths (50%) occurred in men; all 12 deaths occurred in whites. Direct invasion into vital structures was documented in 2 cases at the time of presentation and was documented later in the course of malignancy in all but 3 cases. No cases of metastatic BCC were confirmed, although 1 death in which there was radiographic evidence of metastatic spread of a BCC originating on the leg was categorized as a probable NMSC death. Median survival from the time of initial diagnosis was 61 months. A specific antecedent condition (a chronic leg ulcer) was identified in 1 case. Most (83% [10/12]) of deaths appeared to be related to sun exposure by virtue of their origin on sun-exposed skin and the lack of evidence for another cause. The Rhode Island BCC mortality rate is estimated at 0.08 (0.13 in men and 0.06 in women). The mortality rate ratio of nongenital SCC to BCC is 3.6 (3.8 in men and 3.0 in women). Mortality from nongenital SCC and BCC increased with age and was highest among persons 85 years and older (Table 3).
Other Nongenital NMSC
An additional 13 deaths (6 confirmed and 7 probable) were caused by other histological types of tumors including dermatofibrosarcoma protuberans in 1 case, Merkel cell carcinoma in 4 cases, sweat gland carcinoma in 2 cases, malignant fibrous histiocytoma of the skin in 2 cases, non–AIDS-related Kaposi sarcoma in 1 case, and 3 additional cases of uncertain histological type. The Rhode Island mortality rate is estimated at 0.09.
Vulvar Carcinoma
Vulvar carcinoma was the cause of 53 deaths (32 confirmed and 21 probable). Primary lesions were commonly identified on the labia majora, labia minora, or clitoris. We found documentation of specific antecedent conditions including human papillomavirus infection in 1 case, Bowen disease in 1 case, leukoplakia in 2 cases, lichen sclerosis in 1 case, and another noncutaneous malignancy in 1 case. In 6 cases, documentation of unreasonable delay in seeking medical treatment was identified. Metastatic disease was diagnosed at the time of presentation in 11 cases, of which 3 also had evidence of unreasonable delay. The median age at the time of diagnosis was 78 years (range, 34-103 years); the corresponding age at death was 80 years (range, 40-93 years). The median time to death was 1.2 years after diagnosis. Of the 53 tumors, 7 (13%) were well differentiated, 6 (11%) were moderately differentiated, and 10 (19%) were poorly differentiated; detailed histological data were not available in 30 cases. The Rhode Island mortality rate for vulvar carcinoma is estimated at 0.56. Mortality increased with age and was highest among persons 75 years and older.
Penile Carcinoma
Penile carcinoma was the cause of 12 deaths (10 confirmed and 2 probable). An additional case of SCC of the scrotum was identified. Primary lesions occurred most commonly on the glans and shaft. Information on circumcision was poorly documented. We found documentation of specific antecedent conditions including human papillomavirus infection (2 cases), Bowen disease (1 case), and erythroplasia de Queyrat (1 case). In 3 cases, unreasonable delay in seeking medical treatment was documented; the same number of cases presented with evidence of metastatic disease. The median age at the time of diagnosis was 67 years (range, 49-86 years) and the median age at death was 71 years (range, 53-87 years), although there was no significant difference between these age groups (P = .57). The median time to death was 1.4 years after diagnosis. Of the 10 confirmed tumors arising on the penis, 2 (20%) were well differentiated, 40% (4/10) were moderately differentiated, and 40% (4/10) were poorly differentiated. The Rhode Island mortality rate for penile carcinoma is estimated at 0.24. Mortality increased with age and was highest among individuals 85 years and older (Table 3).
COMMENT
The adjusted (to the 2000 US standard) Rhode Island mortality rate for NMSC is estimated at 0.91. Half of these deaths were caused by genital carcinoma. Greater than half of all deaths attributed to nongenital NMSC were misclassified. The proportion of misclassified deaths was highest for ICD-9 code 173.4 (92%) and written cause "squamous cell carcinoma of the head and neck" (92%). There was considerably less misclassification into other diagnostic categories. In many cases there was evidence of significant psychiatric morbidity or delay in seeking treatment. No confirmed deaths occurred in organ transplant recipients. Skin cancers originating on the ear contributed to greater than 25% of deaths caused by nongenital NMSC.
The present study is limited by several factors. The foremost is the limited detail available from retrievable medical records. An autopsy was performed in only 1 case, although detailed histopathological information was available in most cases. Strict criteria were used to categorize deaths as confirmed, probable, multifactorial, or indeterminate. Only confirmed deaths were included in the analysis of misclassified cases, whereas both confirmed and probable cases were included in mortality rate calculations. Owing to the nature of this study, it was not possible to ascertain the proportion of deaths caused by NMSC that were misclassified under other causes of death. In addition, deaths attributed to NMSC of the perianal skin (154.3) as well as deaths attributed to cutaneous lymphomas (ICD-9 202.1 and 202.2) were not included.
Based on results from the present study, the Rhode Island nongenital SCC mortality rate (adjusted to the US 1970 population) is estimated at 0.21 for the current period compared with 0.26 for the previous period (1979-1987).3 The estimated rates for men and women for the current period are 0.35 and 0.12, respectively, compared with 0.49 and 0.13 for the earlier period. The BCC mortality rate for the current period is estimated at 0.05 compared with 0.10 for the earlier period. Hence, the BCC and nongenital SCC mortality rates appear to be declining over time in Rhode Island. Similar findings have been reported in Finland and in Australia.4-5
The proportion of deaths misclassified as nongenital NMSC for the current period (57%) was similar to that of the earlier period (54%).6 Most of the misclassified deaths were caused by SCC arising from mucosal surfaces in the head and neck (73%). These misclassified deaths were most commonly coded under the ICD-9 173.4 rubric (92%), but rubrics 140 to 149 would have been correct in most of these cases. In the present study, the proportion of misclassified cases was significantly lower for deaths attributed to genital carcinoma in both men (17%) and women (19%) compared with nongenital SCC (P<.001). Previous studies examining the proportion of deaths falsely attributed to NMSC suggest that the problem of misclassification is not confined to the United States.7-8
The period from 1988 through 2000 includes the year in which public health departments began using the ICD-10 for cause of death certification rather than the ICD-9. Deaths attributed to NMSC during 1988 to 1998 were coded under ICD-9 rubrics; the years 1999 to 2000 correspond to ICD-10. The proportion of correctly classified deaths under the ICD-9 173 rubric (38%) increased under the corresponding ICD-10 C44 rubric (64%), although this difference did not reach statistical significance. Of note, 2 deaths attributed to BCC were caused by SCC of the skin. Coding rubrics for ICD-9 and ICD-10 do not permit differentiation of BCC from SCC. In addition, 1 death that was attributed to 184.0 (carcinoma of the vagina) was caused by NMSC of the vulva. The correct ICD-9 code would have been 184.4. It is assumed that the number deaths caused by NMSC that are misclassified under non-NMSC rubrics is low. However, with the exception of deaths attributed to code 184.0, we did not investigate this potential source of misclassification. Nevertheless, estimated mortality rates must be interpreted with appropriate caution.
The incidence of SCC and BCC in Rhode Island has not been directly measured. However, incidence data for the nearby state of New Hampshire are available from a recent population-based study, although genital carcinomas were not included in this investigation.2 The incidence rate ratios of nongenital SCC to BCC were 0.3 in men and 0.2 in women. By contrast, the corresponding mortality rate ratios in Rhode Island were 4.1 in men and 2.6 in women. Hence, these data indicate that case fatality for nongenital SCC is substantially higher than that for BCC.
We are unaware of previous population-based estimates of mortality rates for genital carcinomas. The Rhode Island mortality rates for vulvar and penile carcinomas suggest that mortality due to genital NMSC represents nearly half of all deaths caused by NMSC in Rhode Island. In addition, while men are twice as likely to die from nongenital SCC than from genital SCC, women are more than 3 times as likely to die from vulvar carcinoma than from nongenital SCC. Nevertheless, efforts by the dermatology community to promote primary prevention of human papillomavirus infection in the United States pale in comparison to those promoting reduction of exposure to UV light. Leaders in the dermatology community need to recognize the risk of mortality from genital carcinoma and place greater emphasis on strategies to prevent it.
The challenges to conducting population-based mortality studies are readily apparent. Although Rhode Island is the smallest state in the United States, considerable difficulty was encountered with respect to medical record accrual. Because of space limitations, several medical institutions have an ongoing schedule for the destruction of medical records. More medical care is being delivered in an outpatient setting, which often promotes a decentralized system of record keeping. Some European countries continue to maintain detailed national cancer registries that can be cross-referenced with cause of death registries, yielding a powerful tool for conducting epidemiology research. Obvious concern over privacy of medical records in the United States has led to increased regulatory burdens that inhibit the creation and use of centralized health information databases for approved research purposes.
Mortality is one critical measure of the public health impact of disease. For NMSC, the accuracy of cause of death certification must be improved to ascertain trends in mortality more reliably. This study also underscores the importance of genital skin cancer and suggests that the dermatology community could be a forceful advocate for its prevention and early detection.
AUTHOR INFORMATION
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Correspondence: Martin A. Weinstock, MD, PhD, Dermatoepidemiology Unit, VA Medical Center—111D, 830 Chalkstone Ave, Providence, RI 02908 (maw{at}brown.edu).
Accepted for publication January 5, 2004.
This study was supported by the Medical Student Fellowship from the American Dermatological Association, Millwood, NY (Mr Lewis), and grant CSP402 from the Department of Veterans Affairs and grant 78800 from the National Cancer Institute, Bethesda, Md (Dr Weinstock).
We would like to acknowledge the contribution of Suleka Neelagaru, BS, in acquiring death certificates. John Fulton, PhD, extracted data from the Rhode Island cancer registry and facilitated access to death certificates. Numerous people in medical records departments at hospitals across Rhode Island provided an invaluable contribution through the acquisition of patient medical charts.
From the Dermatoepidemiology Unit, Veterans Affairs Medical Center, and the Department of Dermatology, Rhode Island Hospital and Brown Medical School (Mr Lewis and Dr Weinstock), and the Department of Community Health, Brown University (Dr Weinstock), Providence, RI. The authors have no relevant financial interest in this article.
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