This report summarizes the incidence, relative frequency distributions and survival & mortality by age, sex, stage and grade, of adult invasive primary cancers of the lip in two entrant time-periods as recorded in the SEER Program of the National Cancer Institute for diagnosis years 1973-2014 (SEER Stat 8.3.5). While the occurrence rates and frequency are low in the United States, they are exceptionally important from a clinical and surgical standpoint because of the morphological and functional changes involved.
Background and Importance.—Lip cancers account for 8.8% (19,213) of all oropharyngeal cancers (218,066) and 0.22% of all cancers (8,651,577) in the National Cancer Institute's SEER frequency database, 1973-2014,1 and a total of 10,599 cases in the SEER survival database.2 Mean age by sex in males and females was 65.7 and 69.7-years, respectively, and by race in whites and blacks was 66.6 and 59.7-years, respectively. This particular cancer is more common in males than females (male-to-female ratio 3.9:1) and by race, far more common in whites than in blacks (white-to-black ratio 91.3:1). While the occurrence rates and frequency are low in the United States, they are exceptionally important from a clinical and surgical standpoint because of the morphological and functional changes involved. Ninety percent of lip cancers occur on the lower lip and epidermoid carcinoma is the most common histologic type. Solar radiation, tobacco and alcohol use are well-established causes of for the development of lip cancer.
Objective.—This is a retrospective population-based cohort study using the statistical database of SEER*Stat 8.3.53 (produced 3/5/2018 for diagnosis years 1973-2014) to assess, determine, compare, and summarize the occurrence, long-term survival, and mortality indices of 19,215 patients with lip cancer by age, sex, race, stage, grade, disease duration, in two cohort entry time-periods, 1973-1994 & 1995-2014.
Methods.—Population-based data from SEER registries (released March 6, 2018), previously cited, were analyzed. Standard life table methodologies for converting SEER survival data to comparative mortality and explanations of cancer staging and grading procedures are described in previous Journal of Insurance Medicine articles4,5 and other publications.6,7 Excluded were all death certificate only and those alive with no survival time. The percentage of microscopically confirmed malignant behavior cancers for case selections was 100%.
Statistical significance: Standard errors are shown for survival rates in the SEER survival tables. Actuarial method: Ederer II method is used for cumulative expected survival. Ederer II method calculates the expected survival rates for patients under observation at each point of follow-up, so the matched individuals are considered to be at risk until the corresponding cancer patient dies or is censored.8 Confidence interval: Log (-Log ()) Transformation; the level is 95%. Poisson confidence intervals at the 95% level based on the number of observed deaths are used in this study but not displayed here to conserve space on the mortality tables.
Incidence and survival rates were obtained from the most current database SEER Cancer Statistics Review (CSR),9 and prevalence counts are based on the average of 2014 and 2015 population estimates from the US Bureau of the Census.
Results.—This report summarizes the incidence, relative frequency distributions and survival & mortality by age, sex, stage and grade, of adult invasive primary cancers of the lip in two entrant time-periods as recorded in the SEER Program of the National Cancer Institute for diagnosis years 1973-2014 (SEER Stat 8.3.5). Shifts in trends over time are identified, and the findings are correlated with prognosis, including short and long-term observed (actual), expected & relative survival, median survival, mortality rates & excess death rates per 1000 people.
Conclusions.—Trends in SEER incidence, survival & mortality by sex, race and ethnicity, and relative frequency & percent distribution of lip cancer were analyzed to provide an epidemiologic and medical-actuarial risk assessment for invasive cancer of the lip in the 1973-2014 time-frame.
In 2015, there were 0.73 per 100,000 observed new cases of lip cancer, 0.1 deaths per 100,000 in those cases age 65 and above; and 94.1% (male & female, all stages & grades combined) surviving 5-years in the United States (Chart 1).
Limited available data in Chart 2 indicates that incidence rates increase with age and vary by sex and race in the United States. Incidence is higher in males than in females, higher in whites than in blacks, and higher in the United States than the average elsewhere in the world.
Seer Case Statistics
Chart 3 indicates that after exclusion of cases with no follow-up (FU) or exclusion if the diagnosis was made by death certificate only or autopsy only, the total number of the cases characterized above for which mortality and survival data were available per cohort entry period was reduced to 10,599 (55.2%) out of 19,213 cases, with about the same percentage male-female sex distributions as in the SEER frequency database. The above numbers do not include in situ or unstaged cancers. The combinations of stage, grade, age and race have been reduced for lip cancer because of the smaller numbers of deaths. SEER historic coding was used for stage (localized, regional, distant) in Tables 1-3 and comparative mortality and survival data are given in two cohorts, 1973-1994 and 1995-2014. All of the tables show not only observed data, but also indices of comparative mortality, the mortality ratio (MR) and excess death rate (EDR), and the index of comparative survival, the survival ratio (SR).
Epidermoid carcinoma was the most common histologic type of lip cancer accounting for greater than 95% of all invasive neoplasms; the remainder were constituted primarily by adenocarcinoma and minimally by sarcomas. The age-adjusted incidence rate of lip cancer for females (0.3 per 100,000) is approximately one fourth that for males (1.1). The much lower rates for blacks (0.1) compared with those for whites (0.8) are due to a relative absence of epidermoid cancers in blacks and a much higher incidence of adenocarcinoma than in whites.
Procedures followed by the SEER registries were so effective that loss rates due to patients not being traced were minimal. Follow-up for males was 98.5% complete and for females, 96.5%.
Table 1 shows results for local cancer of the lip in the entire 1973-2014 cohort, by sex and age groups <65 and 65 up. Excess mortality was relatively modest, and tended to increase with duration, especially in men, in whom EDR for all ages was negative in the first year, then increased progressively from 6.0 per 1000 per year at 1-2 years to 18.3 at 15-20 years. At 0-5 years male, all ages, EDR was 6.2 per 1000, MR was only 115% and SR was 96.7%. Excess mortality was slightly higher in men over 65. The pattern of excess mortality by duration in women was more irregular, and exposure was too small in patients under 65 to detect any age trend.
Table 2 shows results by sex and age for regional & distant stages cancer of the lip in the total 1973-2014 cohort. With fewer than 15% of all invasive cases of lip cancer in the regional and distant stages, we have combined males and females for the age groups in regional cancer, and shown only all ages combined for the 85 cases of distant stage. In regional cancer the highest EDR value occurred in the second year: 41 per 1000 per year at ages <65, 80 in those age 65 up, with MR values of 503% and 208%, respectively. For M&F, all ages combined, EDR was lower and rather stable at durations 2-15 year and lowest at 15-20 years, 23 per 1000 per year. For duration 0-5 years in the handful of distant cases EDR was 135 per 1000, MR was 448%, SR down to 53%. There were only 38 survivors at five years out of 85 entrants, however, the width of the confidence interval is more than 25% larger than if the normal approximation was applied.
In Table 3, compared are results for subgroups of sex matched by a combination of stage and grade, all ages combined, in two cohorts, 1973-1994 & 1995-2014, and by race, local stage, all grades combined. Results are for 0-5 and 5-10 years of duration. Because of small numbers of cases. the distant stage is omitted and in the regional stage all grades have been combined. Due to small exposures, comparisons by sex and race were not statistically significant at the 95% confidence interval. Differences by grade by were not significant; excess mortality was randomly higher in 1995-2014 than in 1973-1994. There is no statistically significant increase in MR above 100% for any of the 1995-2014 local subgroups.
Cancer of the lip is characterized by a very low incidence (less than 0.3% of all cancers in the SEER database), a high predominance of epidermoid carcinoma as the histological type, male and female mean age in excess of 66 years, with a wide male-female differential, 66 and 70-years, respectively. The median age at diagnosis was lower for blacks than whites, but this dissimilarity may reflect, in large part, the lower median age of the Black or African American population (33.4 years) compared to the White Alone population (43.1 years) in 2014 (American Community Survey, US Census Bureau, 2006-2014).
Cancer of the lip is a conspicuously visible tumor in its early stages. Doubtless this accounts for the fact that approximately 85% of the cases are localized, with a relatively favorable prognosis. As shown in Table 1 the MR at duration 0-5 years averaged 152% for males under 65, and only 109% for those age 65 up. The corresponding MR values for females were 197% and 112%, respectively. There were only 467 cases of women under 65 with lip cancer from 1973-2014, with 93 total deaths and 23 deaths within 5 years. For men the trend in EDR was a slight increase with age and duration.
Excess mortality in regional lip cancer is also much lower than it is in most other cancer sites (Table 2). The average EDR for males & females, all ages combined at 0-5 years duration was only 40 per 1000 per year, and this decreased by duration, with excess mortality at 15-20 years of 23 per 1000 per year. There were only 85 cases of distant cancer, with a 20-year total of 60 observed and 26.2 expected deaths.
Not shown, but by cohort, excess mortality in lip cancer was significantly lower for males & females, all ages, stages and grades combined in 1973-1994 (10.9 per 1000 per year; 30,965.5 patient-years exposure) than in 1995-2014 (12.4 per 1000 per year: 14,885.5 patient-years exposure). Grade 3&4 cases were too few to make any valid comparison of mortality by grade.
Profound appreciation to my esteemed colleague Dr. Richard B. Singer, M.D. (deceased) for his friendship, invaluable collaboration and scholarly expertise, encouragement and assistance in the initial (unpublished) iterations of long-term comparative mortality and survival in cancers of the lip in 2003.