GYNECOLOGIC ONCOLOGY A population-based study of selected demographic characteristics of Israeli-Jewish women with cervical squamous cell carcinoma Joseph Menczer • Liron Kogan • Eduardo Schejter • Irena Liphshiz • Micha Barchana Received: 18 February 2010 / Accepted: 28 June 2010 / Published online: 10 July 2010 � Springer-Verlag 2010 Abstract Purpose The age-standardized incidence rate (ASR) of invasive cervical cancer in Israeli-Jewish women is per- sistently low compared to many other countries. The aim of the present study was to assess selected demographic characteristics of Israeli-Jewish women with cervical squamous cell carcinoma (SCC) in an attempt to identify current selected risk factors. Method Included were all histologically confirmed SCC patients diagnosed during 2002–2004 according to the Israel National Cancer Registry. Demographic and popu- lation data were obtained from the Central Population Registry and from the Israel Central Bureau of Statistics annual abstract reports. The ASR and incidence rate for each demographic category were computed. Results During the study period, 350 SCC patients (mean age 50.3 years) were diagnosed (ASR of 3.8/100,000). High SCC incidence rates of single women 40?, of mar- ried women 30? years old and of divorced and widowed women in the 40–49 age group were found. The mean number of children was 2.1 (range 0–9). Compared to the population the rate of childless patients in the 50? age group, that of patients with 1–2 children in the 40–49 age group and that of North-African-born patients was signif- icantly higher. No excess rate was found for multiparity and low socioeconomic status. Conclusion High incidence rates of SCC were observed for some age groups of single and married women, for women without children or 1–2 children and for North- Africa-born women. Great differences between age groups within each demographic category were observed. Keywords Cervical squamous cell carcinoma � Israeli-Jewish women � Demographic characteristics Introduction The age-standardized incidence rate (ASR) of invasive cervical cancer in Israeli-Jewish women is persistently low (5.6/100,000) compared to that in many other countries [1]. It is well established that oncogenic human papillomavirus (HPV) is the primary cause of cervical cancer [2]. How- ever, other cofactors, including sexual habits, reproductive and environmental factors, are necessary for progression from cervical HPV infection to cancer [3]. In Israel, cytological screening for detection of cervical cancer is opportunistic. The exact percentage of women screened and the rate of HPV infection of Israeli women is unknown. Older studies have shown that in Jewish women some cofactors are alike to other communities. Thus Martin in 1967 [4] compared 40 American-Jewish cervical squamous cell carcinoma (SCC) patients to 36 controls and found a significant younger age at coitarche and a higher number of J. Menczer (&) Department of Obstetrics and Gynecology, Gynecologic Oncology Unit, E. Wolfson Medical Center, Holon, Israel e-mail:
[email protected] L. Kogan Department of Obstetrics and Gynecology, The Hadassah Ein Kerem University Medical Center, Jerusalem, Israel E. Schejter Colposcopic Clinic, Maccabi Health Services, Tel Aviv, Israel I. Liphshiz � M. Barchana National Cancer Registry, Jerusalem, Israel 123 Arch Gynecol Obstet (2011) 283:629–633 DOI 10.1007/s00404-010-1582-2 coital partners among the cases than among the controls. Pridan et al. in [5] compared 222 Israeli-Jewish SCC patients diagnosed during an 18-year period to 424 con- trols. They also found that cases commenced sexual rela- tions at an earlier age and had a higher number of partners compared to controls. In addition they found that more women in the control group fell into a higher social class than cases when judged by father’s occupation. The aim of the present population-based study was to assess selected current demographic characteristics of Israeli-Jewish women with SCC. Materials and methods The study group includes all women with histologically confirmed SCC diagnosed during the 3-year-period 2002– 2004. The diagnosis was based on the original pathology report. The number of non-Jewish women (74 women) was too small for meaningful analysis. The present study is therefore restricted only to Israeli-Jewish women. Data were obtained from the Israel National Cancer Registry (INCR). This registry was established in 1960 and is population-based, covering the entire Israeli population. Notification became mandatory in 1982 by a ministerial decree. All malignant tumors as well as benign brain tumors are being collected, and information sources include all hospitals including oncology departments, discharge records, surgical and pathology reports, death certificates, as well as privately owned pathological and other institutes that diagnose and/or treat cancer patients. A comprehensive survey carried out in 1991 revealed that the completeness of the INCR of solid malignant tumors was above 95% [6]. The INCR retrieves each patient’s demographic data from the Central Population Registry using the personal identification number that is being assigned to all citizens upon birth or immigration. Population data were obtained from the Israel Central Bureau of Statistics (ICBS) annual abstract reports for the study period [7]. The characteristics assessed were the only ones available. The ICBS ranks selected geographical areas, i.e., neighborhoods, localities, regional councils; statistical areas, according to their socioeconomic status (SES), based on a set of demographic, social and economic variables, and creates a socioeconomic index (SEI) from 1 (low SES) to 20 (high SES) [8]. In order to minimize the confounding effect of age, the SEI of cases and of the population was assessed only for the age group 30–59. The age-standardized incidence rate (ASR) per 100,000 was computed using the world standard population as reference. Incidence rates were calculated for selected demographic variables using as a reference the entire Israeli-Jewish female population in the same age range as the SCC patients. Differences were compared by the chi-square test and a P value of \0.05 was considered as significant. Corrected P values were computed based on the Bonferroni method in order to take into account multiple comparisons, when performed. Results Overall 456 cervical cancer patients were registered dur- ing the study period (360, 51, 17, 6, and 32 patients with squamous cell carcinoma, adenocarcinoma, adenosquamous carcinoma anaplastic carcinoma and unspecified carcinoma patients, respectively). Of the total group of 360 recorded SCC patients, in 10 the pathology report could not be located and they were excluded from the study. The present analysis is thus based on the remaining 350 patients. The ASR of SCC during the study period was 3.8/100,000 and the median age of the patients was 50.3 (range 22–93) years. None of the patients were younger than 20 years. Table 1 presents the distribution of SCC patients and of the population by age groups and age-specific incidence rates of SCC. Statistically significant differences in the distribution of the study group and the general population as well as in the specific rates between the different age groups were observed. The lowest rate was found in the 20–29 age group and the highest in the 40–49 age group. The percentage of SCC patients aged less than 30 years was significantly lower; the percentage of patients in the 40–49 age group was significantly higher than their respec- tive percentages in the general population. Among the SCC patients the percentage of single, mar- ried, divorced and widowed women was 5.4, 50.3, 29.7 and 14.9, respectively. The incidence rates for SCC patients Table 1 Distribution of SCC patients and general population by age groups and age-specific incidence rates of SCC Age group SCC no. (%) Population no. (%) Age-specific incidence rate/105* Total 350 (100.0) 1,820,700 (100.0) 20–29 15 (4.3) 406,600 (22.3) 3.69 30–39 66 (18.9) 344,100 (18.9) 19.18 40–49 91 (26.0) 307,700 (16.9) 29.57 50–59 68 (19.4) 313,900 (17.2) 21.66 60–69 49 (14.0) 187,900 (10.3) 26.08 70? 61 (17.4) 260,500 (14.3) 23.42 SCC squamous cell carcinoma patients * Overall differences between age-specific rates: P \ 0.0001 630 Arch Gynecol Obstet (2011) 283:629–633 123 according to marital status and by age groups are presented in Table 2. The incidence crude rate of single women was significantly lower than the rate of women with other marital status (5.22, 16.27 and 39.53 per 100,000 among single, married and divorced/widowed women, respectively). Sig- nificant differences were observed in the age-specific inci- dence rates in each marital status (P \ 0.0001, P = 0.001 and P = 0.0003 for single, married and divorced/widowed women, respectively). Among single and married women, the lowest incidence rate was observed in the 20–29 age group (1.29 and 4.98, respectively). More than 60% of the single SCC patients were diagnosed at age 40 and older while only 15% of the single women in the general popu- lation were in the 40? age group. The percentage of divorced/widowed women in the 40–49 age group was almost twice than the rate in the general population (25.2% compared to 13.7%, respectively, P \ 0.001). The mean number of children of SCC patients was 2.1 (range 0–9). The distribution of SCC patients and the general population according to number of children and by age group is presented in Table 3. In total, the percentage of patients without children and that of patients with 1–2 children was lower compared to the population, (24.1% compared to 19.8% and 36.4% compared to 40.5%, respectively) but did not reach statistical significance (P = 0.098). Regarding the age distribution, in comparison to the general population, significant differences were observed in both patients without children and with 1–2 children but not in those with 3 or more children (P \ 0.0001, P = 0.007 and P = 0.23, respectively). The Bonferroni-corrected P values show significantly higher percentages in the 50? age groups in patients without children and in the 40–49 age group in SCC patient with 1–2 children compared to those in the general population (P \ 0.001 and P = 0.04, respectively). Table 4 presents the incidence rates of patients according to place of birth showing significantly higher rate of SCC among the North-African-born compared to the rates of the other origin groups. The rate of patients of other origin was not significantly different than in the population. The SES analysis could only be assessed for 151 (43.1%) patients since in the rest of them the place of residency was not included in the ICBS SEI ranking or they were younger or older than 30–59 years. The distribution of these patients according to SES is presented in Table 5. No significant differences were observed in the distribution of SCC patients and the population by SES categories. Table 2 Age-specific incidence rates of SCC by marital status Single Married Divorced/widowed SCC, n = 18 (%) Population, n = 325,900 (%) Rate/105 SCC, n = 175 (%) Population, n = 1,075,400 (%) Rate/105 SCC, n = 155 (%) Population, n = 392,100 (%) Rate/105 20–29 16.7 71.5 1.29 4.6 14.9 4.98 2.6 2.6 40.0 30–39 22.2 13.4 9.17 25.7 23.7 17.66 10.3 9.1 44.82 40–49 22.2 6.2 19.80 27.4 22.0 20.30 25.2 13.7 72.76 50? 38/9 8.9 20.62 42.3 39.4 17.47 61.9 74.7 32.79 P \0.0001 0.001 0.0003 In two patients and 27,300 women in the population—marital status was unknown SCC squamous cell carcinoma patients Table 3 Distribution of SCC patients and general population by age groups and parity Age group Number of children 0 1–2 3? SCC no. (%) Pop. no. (%) SCC no. (%) Pop. no. (%) SCC no. (%) Pop. no. (%) Total 84 (100) 50,357 (100) 127 (100) 102,943 (100) 138 (100) 100,955 (100) 20–29 5 (6.0) 34,253 (68.0) 9 (7.1) 16,796 (16.3) 1 (0.007) 3,013 (3.0) 30–39 8 (9.5) 5,584 (11.1) 32 (25.2) 23,248 (22.6) 26 (18.8) 22,519 (22.3) 40–49 7 (8.3) 3,392 (6.7) 35 (27.6) 19,490 (18.9) 49 (35.5) 30,702 (30.4) 50? 64 (76.2) 7,123 (14.1) 51 (40.2) 43,409 (42.2) 62 (44.9) 44,721 (44.3) P \0.0001 0.007 0.23 Based on a representative 20% population sample SCC squamous cell carcinoma patients, Pop. population Arch Gynecol Obstet (2011) 283:629–633 631 123 Discussion The ASR (3.8/100,000) of SCC in the present study con- firms again the relatively low incidence of this malignancy in Israeli-Jewish women. The median age of the patients (50.3) was similar to that in other population-based studies and, as in population-based studies from other countries [9], higher incidence rates of SCC were found in women older than 40 years. In our study 23.1% of SCC patients were less than 40 years old while in the general population 41% were less than 40 years old. We found high incidence rates of single SCC patients older than 40 years and of married patients more than 30 years old. These lower rates may be related to factors which characterize preceding life periods in the older women. In married women more than 30 years old the excess may also be related to marriage or first pregnancy at a young age. The data with regard to these factors were not available to us. The percentage of divorced/widowed patients was significantly higher in the 40–49 age group than in the population, while in the age group of less than 40 the percentage of patients was similar to that in the population. In studies of other populations an elevated risk for divorced women [10, 11] was found. An elevated risk for widows less than 50 years old [1] was reported in one study, yet in a Norwegian study [10] no overall relation with cancer for widowed women was observed. The reason for the differ- ences between marital status patterns in our study and between our study and other studies is not clear. It may be related to different sexual behavior, differences in HPV exposure, and other cofactors. Generally rates varied in age groups within each marital status category. Multiparity has been found in many studies to be associated with SCC [12]. In the pooled analysis of the International Agency for Research on Cancer Multicentric Cervical Cancer Study, the odds ratio for SCC in women with seven or more full-term pregnancies was fourfold higher than that in nulliparous women, and the risk increased linearly with an increasing number of full-term pregnancies [12]. It has been proposed that high parity may increase the risk of cervical neoplasia because it maintains the transformation zone on the exocervix for many years [13], facilitating the direct exposure to HPV and, possibly, to other cofactors. And yet, in some studies no association between multiparity and cervical cancer has been found [3, 14] especially when adjusting for the age at first birth [15]. In line with these studies, we also found that the rate of SCC patients with 3 or more children was statistically not different than in the population. Rates varied greatly with age within each parity group. In addition we found an excess rate of patients without children and in those with 1–2 children only in certain age groups. The population of Israel consists of various ethnic sub- groups that have emigrated from various countries and continents where they have lived for many centuries. Each of these diverse populations coming from distinct geo- graphical areas is characterized by some unique genetic disease, lifestyle habits, and exposures [16]. Therefore, medical, demographic, social, political, and other statistics are reported by ethnic origin grouped according to conti- nent of birth and Israeli-born women. Previous population based studies have shown that the incidence of SCC among Israeli-Jewish women born in North Africa (N. Africa) and among their descendents [17] is significantly higher than among other ethnic groups, possibly due to genetic factors [18]. A significantly higher incidence rate of N. African-born SCC patients as com- pared to those of other origin was found in the present study as well. Many studies in different populations indicate that women of low SES have a higher than average risk of cervical cancer [19, 20]. In the current study no association between low SES and SCC was observed in our popula- tion. This is contrary to the findings in an older study of Israeli-Jewish women [5]. This may possibly be attributed to the universal compulsory government-funded health care for all Israeli citizens. Accordingly the low and high SES populations have equal access to health care. Table 4 Incidence rates of SCC in women aged over 20 years by place of birth Place of birth SCC n = 350 (%) Populationa n = 1,819,500 (%) Incidence rate/105 P* Israel 45.4 53.6 16.3 Europe/America 30.0 31.9 18.1 North Africa 17.7 8.4 40.6 \0.0001 Asia 6.9 6.1 21.5 a In 1,200 women place of birth unknown * North Africa versus Israel, Europe/America P \ 0.001 and versus Asia P = 0.06 after Bonferroni correction for multiple comparisons Table 5 Distribution of SCC patients and general population aged 30–59 years according to socioeconomic index SEI SCC no. (%) Population no. (%) P Total 151 (100.0) 745,630 (100.0) \5 7 (4.6) 28,415 (3.8) 5–8 25 (16.6) 146,263 (19.7) 9–12 54 (35.8) 255,314 (34.2) 0.6 13–15 38 (25.2) 159,704 (21.4) [15 27 (17.8) 155,934 (20.9) SEI socioeconomic index, SCC squamous cell carcinoma patients 632 Arch Gynecol Obstet (2011) 283:629–633 123 The strength of our study is the relatively large number of Israeli-Jewish SCC patients, its population-based nature, and the ability to use data from the INCR. The weaknesses of our study are the limitations inherent in its retrospective nature and the limited number of characteristics recorded in the INCR. Thus data with regard to HPV status, sexual and smoking habits, age at first delivery, oral contraceptive use and other cofactors that are associated with SCC were not available for assessment. The demographic characteristics, among those assessed in the present study, associated with a significantly increased rate of SCC were single women aged more than 40 years, married women more than 30 years old and divorced/widowed patients 40–49 years old, childless patients in the 50? age group patients with 1–2 children in the 40–49 age group and that of N. African-born patients. The age distribution of multiparous SCC patients was not different from the age distribution in the population. Great differences between age groups within each demographic category were observed. Further population-based studies of clinical and demo- graphic characteristics of Israeli-Jewish SCC patients are indicated. Conflict of interest statement None. References 1. (2002) Cancer in five Continents. Volume VIII. IARC Scientific Publication No. 155, Lyon 2. Schiffman MH, Castle P (2003) Epidemiologic studies of a necessary causal risk factor: human papillomavirus infection and cervical neoplasia. 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Cancer Epidemiol Biomarkers Prev 13:1574–1582 Arch Gynecol Obstet (2011) 283:629–633 633 123 A population-based study of selected demographic characteristics of Israeli-Jewish women with cervical squamous cell carcinoma Abstract Purpose Method Results Conclusion Introduction Materials and methods Results Discussion References /ColorImageDict > /JPEG2000ColorACSImageDict > /JPEG2000ColorImageDict > /AntiAliasGrayImages false /CropGrayImages true /GrayImageMinResolution 149 /GrayImageMinResolutionPolicy /Warning /DownsampleGrayImages true /GrayImageDownsampleType /Bicubic /GrayImageResolution 150 /GrayImageDepth -1 /GrayImageMinDownsampleDepth 2 /GrayImageDownsampleThreshold 1.50000 /EncodeGrayImages true /GrayImageFilter /DCTEncode /AutoFilterGrayImages true /GrayImageAutoFilterStrategy /JPEG /GrayACSImageDict > /GrayImageDict > /JPEG2000GrayACSImageDict > /JPEG2000GrayImageDict > /AntiAliasMonoImages false /CropMonoImages true /MonoImageMinResolution 599 /MonoImageMinResolutionPolicy /Warning /DownsampleMonoImages true /MonoImageDownsampleType /Bicubic /MonoImageResolution 600 /MonoImageDepth -1 /MonoImageDownsampleThreshold 1.50000 /EncodeMonoImages true /MonoImageFilter /CCITTFaxEncode /MonoImageDict > /AllowPSXObjects false /CheckCompliance [ /None ] /PDFX1aCheck false /PDFX3Check false /PDFXCompliantPDFOnly false /PDFXNoTrimBoxError true /PDFXTrimBoxToMediaBoxOffset [ 0.00000 0.00000 0.00000 0.00000 ] /PDFXSetBleedBoxToMediaBox true /PDFXBleedBoxToTrimBoxOffset [ 0.00000 0.00000 0.00000 0.00000 ] /PDFXOutputIntentProfile (None) /PDFXOutputConditionIdentifier () /PDFXOutputCondition () /PDFXRegistryName () /PDFXTrapped /False /CreateJDFFile false /Description > /Namespace [ (Adobe) (Common) (1.0) ] /OtherNamespaces [ > /FormElements false /GenerateStructure false /IncludeBookmarks false /IncludeHyperlinks false /IncludeInteractive false /IncludeLayers false /IncludeProfiles false /MultimediaHandling /UseObjectSettings /Namespace [ (Adobe) (CreativeSuite) (2.0) ] /PDFXOutputIntentProfileSelector /DocumentCMYK /PreserveEditing true /UntaggedCMYKHandling /LeaveUntagged /UntaggedRGBHandling /UseDocumentProfile /UseDocumentBleed false >> ] >> setdistillerparams > setpagedevice