Cervical cancer among Asian subgroups in California, 1990-2004 Janet Bates, MD MPH California Cancer Registry NAACCR Annual Meeting Denver, Colorado June 10, 2008

Background National cancer statistics show lower overall cancer rates among Asians in the US Asians have wide variability in countries of origin, immigration history, culture, language, education and SES that influence cancer risk Aggregated cancer statistics for Asians mask important differences among subgroups Limited national cancer data available on Asian subgroups One of the great challenges in cancer surveillance is to document cancer patterns and disparities across a diverse spectrum of racial and ethnic groups. National cancer statistics show that in the US, Asians experience lower cancer rates overall compared to other racial and ethnic groups. The Asian population is comprised of a diverse mix with respect to country of origin, immigration history, culture, language, education, and socioeconomic status, and other factors that may influence cancer burden and risk. The practice of aggregating cancer statistics for the Asian population may mask important differences among the various Asian subpopulations. National data on cancer among subgroups is not readily available.

Asians in California California has largest Asian population of any state 3.7 million Asians = 12% of state population 90% of California Asian population comprised of 6 subgroups: Chinese, Filipino, Japanese, Korean, South Asian, and Vietnamese California has the largest Asian population of any state In 2000, 3.7 million Asians comprised approximately 12% of the states population 90% of the California Asian population is made up of 6 subgroups: Chinese, Filipino, Japanese, Korean, South Asian, and Vietnamese

Study purpose To describe patterns of cervical cancer incidence, mortality, and survival among 6 major Asian subgroups in California

Methods Cervical cancer cases diagnosed among California residents 1990-2004 Included all 6 Asian subgroups and non-Hispanic whites (NHW) Variables: Age (<40, 40-64, 65+ years) SES quintile (composite census-based measure*) Stage (local, regional, distant, unknown) Surgery (none, local, hysterectomy, other) Radiation (none, any) Chemotherapy (none, any) Invasive cervical cancer cases diagnosed in California from 1990-2004 were identified in the California Cancer Registry We included all 6 Asian subgroups and non-Hispanic whites which were used as a referent group Demographic variables included age, categorized into three groups, and socioeconomic status (SES) Briefly, the SES variable is a composite, census based measure. A principal components analysis was used that included census indicators of education, income, occupation, housing and so forth to develop an SES score for each census block group. Quintiles of this SES score were used in the analysis. Clinical variables included stage, categorized as local, regional, and distant according to seer summary stage criteria; and treatment information including surgery, radiation, and chemotherapy *Yost K et al, Cancer Causes & Control, 2001

Methods Cervical cancer incidence rates and trends calculated using SEERstat Cervical cancer survival probabilities (5 and 10 year) calculated using Kaplan-Meier method Multivariate evaluation of survival calculated using Cox proportional hazards modeling, adjusted for stage, age, SES, and treatment factors Cervical cancer incidence and trends data were analyzed in SEERstat Survival probabilities were calculated using Kaplan Meier

Results

Demographic characteristics: age and SES Chinese Filipino Japan. Korean S. Asian Viet. NHW N 485 747 198 309 88 484 10,879 % Age (yrs) * * <40 17.1 18.2 24.8 14.9 6.8 29.9 40-64 47.4 58.0 51.5 57.0 56.8 68.0 48.4 65+ 35.5 23.8 23.7 28.2 25.0 25.2 21.7 SES quintile * 1 (low) 11.6 17.0 8.1 19.4 20.0 12.2 5 (high) 13.0 25.3 21.4 21.6 13.6 21.2 We ended up with a total of 13,190 cases of invasive, histologically confirmed cervical cancer cases. 10,879 of those cases were diagnosed among non-Hispanic whites, and 2311 among the 6 Asian subgroups. The Asian subgroup with the largest number of cases was Filipinos at 747, and the smallest was South Asians at 88. Overall, the age distribution among all 6 of the Asian subgroups was older than that of non-Hispanic whites, who had a higher proportion of cases diagnosed among women under age 40, 29.9% than all of the Asian subgroups, and a lower proportion diagnosed at age 65 + than all the Asian subgroups. The age distributions highlighted in orange were significantly different from NHW at p <.05 – the Chinese, Filipino, Korean, and South Asians. Note that the Chinese had a greater proportion of cases diagnosed at age 65 + years than any other group – 35.5%, and the Vietnamese had the lowest proportion of cases diagnosed at less than 40 years of age at 6.8% There also were significant differences between the Asian subgroups and the non hispanic whites with respect to SES, highlighted in orange. For simplicity, this table only shows the proportion of cases in the lowest and highest SES quintiles, using our census based composite measure. A greater proportion of cases were diagnosed among the lowest SES group in the Filipino, Korean, and Vietnamese groups compared to whites, while among the Chinese a greater proportion of cases were diagnosed among the highest SES quintile compared to NHWs. Cases pop Chinese 484 21.0% 980642 29.8% Filipino 747 32.3% 918678 27.9% Japanese 198 8.6% 288854 8.8% Korean 309 13.4% 345882 10.5% South Asian 88 3.8% 314819 9.6% Vietnamese 484 21.0% 447032 13.6% 2310 3295907 * P for comparison with NHW is significant at < 0.05

Clinical characteristics: stage distribution Chinese Filipino Japan. Korean S. Asian Viet. NHW N 485 747 198 309 88 484 10,879 % Stage * * Local 48.0 45.9 51.0 46.0 44.3 55.0 53.7 Regional 37.5 39.9 36.9 38.5 33.0 37.6 31.3 Distant 6.8 10.4 8.6 9.7 15.9 4.6 10.9 Unknown 7.6 3.8 3.5 5.8 2.9 4.1 The stage distribution was significantly different compared to non-Hispanic whites among Chinese, Filipino, Korean and Vietnamese Cases pop Chinese 484 21.0% 980642 29.8% Filipino 747 32.3% 918678 27.9% Japanese 198 8.6% 288854 8.8% Korean 309 13.4% 345882 10.5% South Asian 88 3.8% 314819 9.6% Vietnamese 484 21.0% 447032 13.6% 2310 3295907 * P for comparison with NHW is significant at < 0.05

Clinical characteristics: stage distribution Chinese Filipino Japan. Korean S. Asian Viet. NHW N 485 747 198 309 88 484 10,879 % Stage * * Local 48.0 45.9 51.0 46.0 44.3 55.0 53.7 Regional 37.5 39.9 36.9 38.5 33.0 37.6 31.3 Distant 6.8 10.4 8.6 9.7 15.9 4.6 10.9 Unknown 7.6 3.8 3.5 5.8 2.9 4.1 The stage distribution was significantly different compared to non-Hispanic whites among Chinese, Filipino, Korean and Vietnamese Lowest proportion of cases diagnosed at local stage were found among South Asian, Filipino, and Korean women; stage distribution among South Asian women not significantly different from NHW Cases pop Chinese 484 21.0% 980642 29.8% Filipino 747 32.3% 918678 27.9% Japanese 198 8.6% 288854 8.8% Korean 309 13.4% 345882 10.5% South Asian 88 3.8% 314819 9.6% Vietnamese 484 21.0% 447032 13.6% 2310 3295907 Lowest proportion of cases diagnosed at local stage were found among South Asian, Filipino, and Korean women; stage distribution among South Asian women not significantly different from NHW * P for comparison with NHW is significant at < 0.05

Cervical cancer incidence trends: 1990-2004 Over the 15 year period 1990-2004, incidence rates declined for all Asian subgroups and for non Hispanic white women.

Cervical cancer incidence trends: 1990-2004 Vietnamese had highest incidence throughout period, as well as most dramatic decline Vietnamese had a higher incidence throughout the 15 year period than any other group, but also experienced the most dramatic decline, with rates declining from 42.6 in 1990-92 to 14.0 in 2002-04.

Cervical cancer incidence trends: 1990-2004 …followed by Korean, then Filipino women Koreans had the second highest incidence, and also a substantial decline from 16.3 to 8.3, followed by Filipino women with a decline from 12.3 to 8.4 over the period

Cervical cancer incidence trends: 1990-2004 Chinese women and NHW had comparable rates in 1990-1992… Chinese and non-Hispanic white women had comparable rates in 1990-1992 at 8.9 and 9.1 respectively

Cervical cancer incidence trends: 1990-2004 …but by 2002-2004 incidence rates were lower among Chinese women By 2002-2004, Chinese incidence rates declined to 4.8, below rates for Non Hispanic whites at 6.6 NHW Chinese

Cervical cancer incidence trends: 1990-2004 Rates among Japanese and South Asian women also declined, but trend not statistically significant Japanese Finally, rates among Japanese and South Asian women also declined but the trends were not statistically significant South Asian

Unadjusted cause-specific 5- and 10-year cervical cancer survival Survival probability (%) (95% Confidence Interval) Chinese Filipino Japanese Korean S. Asian Viet. NHW 5-year 78.6 (74.4, 82.2) 79.0 (75.9, 81.9) 72.3 (64.9, 78.4) 85.7 (80.9, 89.6) 85.8 (75.1, 92.2) 0.79 (0.64, 1.00) 77.5 (76.7, 78.3) 10-year 77.2 (72.9, 81.0) 74.8 (71.2, 78.0) 69.5 (61.7, 76.1) 82.5 (77.1, 86.7) 79.7 (75.4, 83.3) 75.4 (74.6, 76.3) This table shows the results of the unadjusted 5 and 10 year cervical cancer survival probabilities

Unadjusted cause-specific cervical cancer survival Now I will turn to the results of the analyses of survival. South Asian women had the highest unadjusted, cause-specific survival probabilities of 85.8% at both 5 and 10 years, followed by Korean, Vietnamese, then Chinese, Filipino, all with probabilities

Clinical characteristics: stage distribution Chinese Filipino Japan. Korean S. Asian Viet. NHW N 485 747 198 309 88 484 10,879 % Stage * * Local 48.0 45.9 51.0 46.0 44.3 55.0 53.7 Regional 37.5 39.9 36.9 38.5 33.0 37.6 31.3 Distant 6.8 10.4 8.6 9.7 15.9 4.6 10.9 Unknown 7.6 3.8 3.5 5.8 2.9 4.1 Recall the stage distribution slide from earlier – we just saw a higher unadjusted cause-specific survival among South Asians and Koreans compared to other groups, despite a lower proportion of cases diagnosed at local stage. Cases pop Chinese 484 21.0% 980642 29.8% Filipino 747 32.3% 918678 27.9% Japanese 198 8.6% 288854 8.8% Korean 309 13.4% 345882 10.5% South Asian 88 3.8% 314819 9.6% Vietnamese 484 21.0% 447032 13.6% 2310 3295907 Lowest proportion of cases diagnosed at local stage were found among South Asian, Filipino, and Korean women; stage distribution among South Asian women not significantly different from NHW * P for comparison with NHW is significant at < 0.05

Risk of death due to cervical cancer among Asian subgroups Hazard Ratio (95% Confidence Interval) Chinese Filipino Japanese Korean S. Asian Viet. Race only 0.94 (0.78, 1.15) 0.97 (0.83, 1.13) 1.28 (0.97, 1.69) 0.61 (0.45, 0.81) 0.57 (0.32, 1.04) 0.79 (0.64, 1.00) This table shows the results of the multivariate analysis in which variables are added in a stepwise fashion. With only race in the model, we see similarly to the previous slide, that the lowest risk of cervical cancer death compared to non-Hispanic whites was found among South Asians and Koreans; however, the difference is only statistically significant for Koreans where the 95% confidence interval does not include 1 Referent group is Non-Hispanic Whites

Risk of death due to cervical cancer among Asian subgroups Hazard Ratio (95% Confidence Interval) Chinese Filipino Japanese Korean S. Asian Viet. Race only 0.94 (0.78, 1.15) 0.97 (0.83, 1.13) 1.28 (0.97, 1.69) 0.61 (0.45, 0.81) 0.57 (0.32, 1.04) 0.79 (0.64, 1.00) Stage (0.79, 1.18) 0.84 (0.72, 0.98) 1.19 (0.90, 1.56) 0.49 (0.37, 0.66) 0.37 (0.20, 0.66) 0.83 (0.676, 1.03) This table shows the results of the multivariate analysis in which variables are added in a stepwise fashion. After adding stage at diagnosis to the model, the lowest risk of cervical cancer death is still found among So. Asians and Koreans, now statistically significant; the result for Filipinos is now significant. Referent group is non-Hispanic whites

Risk of death due to cervical cancer among Asian subgroups Hazard Ratio (95% Confidence Interval) Chinese Filipino Japanese Korean S. Asian Viet. Race only 0.94 (0.78, 1.15) 0.97 (0.83, 1.13) 1.28 (0.97, 1.69) 0.61 (0.45, 0.81) 0.57 (0.32, 1.04) 0.79 (0.64, 1.00) Stage (0.79, 1.18) 0.84 (0.72, 0.98) 1.19 (0.90, 1.56) 0.49 (0.37, 0.66) 0.37 (0.20, 0.66) 0.83 (0.676, 1.03) Stage, age 0.89 (0.72, 1.09) 0.82 (0.70, 0.95) 1.15 (0.87, 1.52) 0.47 (0.35, 0.62) 0.34 (0.19, 0.62) (0.64, 0.98) This table shows the results of the multivariate analysis in which variables are added in a stepwise fashion. Now with the addition of age, there is little additional change, but the confidence interval for Vietnamese no longer includes 1 Referent group is non-Hispanic whites

Risk of death due to cervical cancer among Asian subgroups Chinese Filipino Japanese Korean S. Asian Viet. Race only 0.94 (0.78, 1.15) 0.97 (0.83, 1.13) 1.28 (0.97, 1.69) 0.61 (0.45, 0.81) 0.57 (0.32, 1.04) 0.79 (0.64, 1.00) Stage (0.79, 1.18) 0.84 (0.72, 0.98) 1.19 (0.90, 1.56) 0.49 (0.37, 0.66) 0.37 (0.20, 0.66) 0.83 (0.676, 1.03) Stage, age 0.89 (0.72, 1.09) 0.82 (0.70, 0.95) 1.15 (0.87, 1.52) 0.47 (0.35, 0.62) 0.34 (0.19, 0.62) (0.64, 0.98) Stage, age, Rx, SES (0.68, 1.02) 0.78 (0.67, 0.91) 1.13 (0.86, 1.50) 0.42 (0.31, 0.57) 0.31 (0.17, 0.56) 0.77 (0.62, 0.96) Finally, with all variables in the model, the pattern we saw in the unadjusted analysis generally holds with South Asians and Koreans having the lowest risk of cervical cancer death; Risk among the Filipino and Vietnamese was also lower than that of non-Hispanic whites. Referent group is non-Hispanic whites

Discussion Higher incidence among Vietnamese, Korean, Filipino women mirror international patterns South Asian rates relatively low despite high rates in countries of origin Overall, we saw higher cervical cancer incidence rates among Vietnamese, Filipino, and Koreans relative to other Asian subgroups and Non-Hispanic whites. This generally mirrors international incidence patterns internationally. The exception was South Asians. Incidence rates were relatively low in this population, whereas rates in India are the highest of any Asian country. This may be related to a relatively high level of education of South Asian immigrants in California compared to other race/ethnic groups.

Discussion Variability in cervical cancer incidence is largely attributed to screening Expect populations with low screening to have higher incidence Examined cervical cancer screening survey data from the California Health Interview Survey (CHIS) When we look at the reasons for variability in cervical cancer incidence, cervical cancer screening is the first place to look. Because cervical cancer screening can lead to the detection and removal of pre cancerous lesions, we would expect that a highly screened population would have a lower incidence of invasive cervical cancer. So we examined the data on cervical cancer screening from the 2003 California Health Interview Survey, or CHIS among Asian subgroups in California.

Percent pap test in past 3 years by Asian subgroup, California Here are the results from CHIS showing the proportion of women reporting having a pap test in the past 3 years. These survey results are for women over the age of 18 who did not report having had a hysterectomy. The lowest prevalence of screening was seen among the Koreans – 67%, followed by Chinese, Vietnamese, South Asians. Filipinos reported the highest prevalence of recent pap testing, 88%, comparable to that of NHW at 88.9%. Source: California Health Interview Survey 2003

Percent pap test in past 3 years and cervical cancer incidence by Asian subgroup, California The red lines show the 3 year age adjusted average incidence rate for 2002-2004 superimposed over the pap test results, and we see no consistent pattern. Korean and Vietnamese women had relatively low utilization of the pap test, and relatively higher cervical cancer incidence rates, which is what we would predict. However, pap utilization reported among Chinese women was also relatively low, but they also had low incidence, which is not what we would predict. Conversely, Filipino women had high pap utilization, but also had higher incidence. So at least on initial examination, there is no obvious correlation. Clearly, these relationships would need to be teased our further with additional evaluation and data.. Source: California Health Interview Survey 2003

Limitations Limited number of cases in some subgroups Misclassification of race is possible Risk factor data (HPV subtypes, smoking, diet, co-morbidities, immigration data, etc.) not available Before concluding, I will note some of the limitations of this study As you saw, some of the analyses were based on a low number of cases in some subgroups Race information is obtained from the medical record and not by self report, so misclassification with respect to subgroup is possible Information of lifestyle factors that may influence cervical cancer risk are not avaiable

Summary Distinct variations among subgroups in patterns of cervical cancer incidence and survival Practice of aggregating statistics for Asians masks these differences Public health programs targeting cervical cancer screening and prevention must take these differences into account To sum up, we found distinct variations in the burden of cervical cancer among our 6 Asian subgroups. These differences are masked by the general practice of aggregating statistics for Asians. Public health programs that target cervical cancer screening and prevention must take these differences into account in order to be successful in reducing the cervical cancer burden among Asians

Summary Lower risk of cervical cancer death among Vietnamese, Korean, Filipino, and South Asian women Few studies on this Further evaluation of reasons for this apparent survival advantage is needed Finally, we found a lower risk of cervical cancer death among Vietnamese, Korean, Filipino and south Asian women, even after adjusting for demographic and clinical factors. There are few studies on this, and further evaluation is needed of this apparent survival advantage.

Acknowledgements Co-authors: Brenda Hofer, Arti Parikh-Patel CDC Cancer supplement coordinators: Meg Watson, Mona Saraiya CCR research and surveillance program staff: Mark Allen, Allyn Fernandez Ami, Sandy Kwong