Incidence trends of cervical cancer in Puerto Rico, 1987-2004.
Abstract: Objective: Cervical cancer was the leading malignancy among women in Puerto Rico when the Central Cancer Registry was first established by law in 1950. The screening program for cervical cancer in PR was initiated in 1961 when cytological laboratories were established in regional hospitals throughout the island, reaching its peak in 1973. In 2004, invasive cervical cancer ranked fifth among the top cancers in women in PR, representing 4% of all newly diagnosed cancers and 2% of all cancer-related deaths among women. The purpose of this study was to evaluate the incidence trends of cervical cancer by histology type in PR.

Methods: Cervical cancer cases (n = 3,516) diagnosed from 1987-2004 were obtained from the Puerto Rico Central Cancer Registry. Age-adjusted and age-specific incidence rates by histological type were calculated. Annual percent changes were estimated to evaluate the incidence trends from 1987 to 2004.

Results: From 1987 to 2004, the incidence of cervical cancer showed a downward trend (APC = -2.1%). Seventy-six percent (76.3%) of invasive cervical cancer cases were squamous cell carcinoma (SCC), 15.4% were adenocarcinoma (ADC), and 8.3% had other histologies. When histology was considered, a decreasing trend was observed for the incidence rates of SCC (APC = -3.2%, p < 0.05), with the greatest decrease being seen in women aged 60-74 (APC = -6.6%, p < 0.05). While the overall incidence rate of ADC remained stable (APC = 0.8%, p > 0.05), it increased in women aged 30-44 (APC = 3.8%, p < 0.05).

Conclusion: Overall, the incidence rates for cervical cancer (SCC in particular), have decreased in PR. However, ADC does not present a similar decreasing trend. This trend, which is similar with other populations, could be explained, in part, by a decreasing prevalence of risk factors. Nevertheless, analysis by specific age group shows variations in the risk, which need careful consideration since they could imply changes in factors associated with each of the histological types. [P R Health Sci J 2010;4:364-371]

Key words: Cervical cancer, Incidence trends, Adenocarcinoma, Squamous cell carcinoma

Objetivo: El cancer de cuello uterino era la principal malignidad entre las mujeres en Puerto Rico (PR) en el ano 1950, cuando el Registro Central de Cancer de Puerto Rico (RCCPR) ffue establecido por ley. En 1961, el Departamento de Salud de PR establecio el programa de cernimiento para cancer de cuello uterino cuando implanto laboratorios citologicos alrededor de la isla, alcanzando su mayor efectividad en el 1973. En el 2004, el cancer de cuello uterino ocupo la quinta position entre los canceres en mujeres, representando el 4% de todos los canceres nuevos diagnosticados y el 2% de todas las muertes por cancer entre mujeres en PR. El proposito del estudio fue evaluar las tendencias de incidencia de cancer de cuello uterino por tipo histologico en PR. Metodos: Los casos de cancer de cuello uterino (n = 3,516) diagnosticados desde el 1987 al 2004 fueron obtenidos del RCCPR. Tasas de incidencias ajustadas por edad y especificas por tipo histologico fueron calculadas. El cambio porcentual anual (CPA) hie estimado para evaluar las tendencias de incidencia desde el 1987 al 2004. Resultados: Desde el 1987 al 2004, la incidencia de cancer de cuello uterino mostro una reduction de 2.1% (p < 0.05) anualmente. El 76.3% de los casos invasivos de cancer de cuello uterino fueron de celulas escamosas, 15.4% fueron adenocarcinoma y 8.3% tenian otras histologias. Cuando se considero tipo de histologia, una reduction en la tendencia me observada para las tasas de incidencia de carcinoma de celulas escamosas (CPA = -3.2%, p < 0.05), con la mayor reduccion en el grupo de mujeres de 60-74 anos (CPA = -6.6%, p < 0.05). Mientras que las tasas de incidencia total de adenocarcinoma permanecio estable (CPA = 0.8%, p > 0.05), aumento en mujeres de 30-44 anos (CPA = 3.8%, p < 0.05). Conclusion: En general, las tasas de incidencia de cancer de cuello uterino (en particular carcinoma de celulas escamosas) han descendido en PR. Sin embargo, el adenocarcinoma no presenta una tendencia descendente similar. Esta tendencia cual ha sido similar a otras poblaciones, podria ser explicada en parte por la reduction en la prevalencia de factores de riesgos. Sin embargo, el analisis por grupo de edad especifico muestra una variation en el riesgo, que necesita ser considerada puesto que podria implicar cambios en los factores asociados a cada uno de los tipos histologicos.
Article Type: Report
Subject: Oncology, Experimental (Analysis)
Squamous cell carcinoma (Risk factors)
Squamous cell carcinoma (Analysis)
Cervical cancer (Risk factors)
Cervical cancer (Analysis)
Cancer (Diagnosis)
Cancer (Analysis)
Cancer (Research)
Cancer (Care and treatment)
Authors: Perez-Irizarry, Javier
Nazario-Delgado, Cruz M.
De la Torre, Taina
Ortiz-Ortiz, Karen J.
Torres-Cintron, Mariela
Figueroa-Valles, Nayda R.
Pub Date: 12/01/2010
Publication: Name: Puerto Rico Health Sciences Journal Publisher: Universidad de Puerto Rico, Recinto de Ciencias Medicas Audience: Academic Format: Magazine/Journal Subject: Health Copyright: COPYRIGHT 2010 Universidad de Puerto Rico, Recinto de Ciencias Medicas ISSN: 0738-0658
Issue: Date: Dec, 2010 Source Volume: 29 Source Issue: 4
Product: Product Code: 8000220 Cancer & Cell R&D; 8000432 Cancer Therapy NAICS Code: 54171 Research and Development in the Physical, Engineering, and Life Sciences; 621 Ambulatory Health Care Services SIC Code: 8731 Commercial physical research; 8733 Noncommercial research organizations
Accession Number: 244280048
Full Text: Cervical cancer is the second most common type of cancer among women in the world, affecting more than 500,000 women worldwide each year (1-2). In developing countries, it occupies the first or second position, while in developed countries it is the seventh most common malignancy (1-2). Every year, 83% of the world's new cervical cancer cases and 85% of all cervical cancer deaths occur in developing countries (2). In 2004, invasive cervical cancer ranked fifth among the top cancers in women in Puerto Rico (PR), representing 4% of all newly diagnosed cancers and causing 2% of all cancer-related deaths among women.

From 1950 to 1993, primary care in PR was provided at the municipal level by government health centers. The municipalities were grouped into seven health regions for the provision of health care at the secondary level. Tertiary care was provided by specialized hospitals located in the metropolitan area of the island. In 1950, the screening program for cervical cancer in PR began with the island's first detection clinic (at the School of Medicine of the University of Puerto Rico). In 1957, the Department of Health of Puerto Rico began the support of screening, and by 1961, the program had established cytology laboratories and trained personnel in all of the regional hospitals throughout the island (3). Population-based data from the Puerto Rico Central Cancer Registry (PRCCR) provided evidence that incidence rates of invasive cervical cancer had been descending since 1950 (4). The decreasing trend has continued into the present, with the exception of a significant increase incidence that occurred between the 1960s to the 1970s when the widespread implementation of the screening program had its highest effect (5). The cytological rates increased from 15.45 per 1,000 in 1962 to 176.67 per 1,000 in 1973, but afterwards the rate of cytological testing linearly decreased (p < 0.001) to 110.92 per 1,000 in 1987. A peak rate (176.67 per 1,000) of cytological tests was observed during the period of 1972-1973 (5). The average incidence rate of invasive cervical cancer (age-adjusted to the PR 1970 population) decreased 59.4% from 24.7 per 100,000 women in 1963-1967 to 10.0 per 100,000 women in 1983-1987 (5). Although descending rates had also been observed in Europe (6) and the United States (US) (7), the risk of cervical cancer for PR as compared to US subgroups populations was similar to Non-Hispanic Blacks, lower than Hispanics, and higher than Non-Hispanics Whites for the period of1998-2003 (8).

The effectiveness of screening programs has been documented in numerous studies (9-12). According to the International Agency for Research in Cancer (IARC), high quality conventional cytological screening programs can reduce the incidence of cervical cancer by at least 80% (13). Nevertheless, lifestyle and risk modifications can also explain the changing trend, in particular in populations with limited access to screening interventions (5, 14-15). As it was stated before, cervical cancer cases are diagnosed with almost twice the frequency in women living in less developed countries when compared to women living in more developed countries (2), an argument in favor of this being a disease associated with poverty. Low socioeconomic level and education attainment imposes a heavier burden on women's health. A significant correlation (p = 0.0103) was observed between increasing socioeconomic level and decreasing cervical cancer rates from 1963 to 1987 in PR (5, 14).

Human Papilloma Virus (HPV) infection (most notably HPV subtypes 16, 18, 31, 33, and 45) is a major risk factor for cervical cancer (16-18). Squamous cell carcinoma (SCC) has been associated with HPV-16, which is the most prevalent type (observed in 50%-60% of cases), while HPV-18 is observed in 10%-20% of cases (18-20). In contrast, HPV-18 plays a major role in adenocarcinoma (ADC), accounting for 40%-60% of cases, while HPV-16 has been observed in 30%-55% of cases (18-20). Different HPV types are associated with SCC and ADC of the cervix, but many cofactors are equally important for both histological types, such as lifetime number of sexual partners, age at first intercourse, oral contraceptive use, and parity (20-29). Nevertheless, smoking (current smokers) has been found to be a strong risk factor for SCC, but not for ADC of the cervix (20-21, 25, 28). Also, infection with Chlamidya trachomatis was associated with SCC, but not with ADC (20, 30-33). Bosch et al. (19), collected cervical cancer specimens from patients around the globe; evaluation by Polymerase Chain Reaction (PCR) revealed the presence of HPV DNA in more than 90% of these specimens. This suggests that HPV could be an important causal factor but that it needs triggering from other risks associated with cervical cancer (17). Other risk factors related to behavior are multiple sexual partners, early onset of sexual activity, lack of sexual protection, and having a history of sexually transmitted diseases. Long term use of oral contraceptives (27, 34), low socioeconomic status (35-36), having a history of tobacco use (24, 28, 37), and poor dietary patterns are also risk factors (38). Changes in the patterns of occurrence in any of these risk factors can affect the incidence of cervical cancer.

Despite the dramatic decrease in incidence and mortality rates, there are, to our knowledge, no published reports on the incidence of cervical cancer by histological type in PR. The aim of this study was to evaluate (by age group and histological type--squamous cell carcinoma, adenocarcinoma, and both) cervical cancer incidence trends in PR residents during the period covering 1987 to 2004.

Methods

Almost ninety-eight percent (97.8%) of all invasive cervical cancer cases diagnosed in PR from 1987 to 2004 and registered by the PRCCR were included in this analysis (39). Of those invasive cervical cancer cases, 97% had microscopic confirmation of disease. About 1% of cervical cancer cases had only a positive laboratory test/serum marker, direct visualization, positive radiology, or clinical diagnosis. In situ carcinomas and cases diagnosed by death certificate only (2.2% of all cases) were not included. Tumors were categorized by histological type, according to the International Classification of Diseases for Oncology (ICD-O-3) (40), as follows: squamous cell carcinoma (codes 8050-8084, 8120), adenocarcinoma (including adenosquamous carcinoma, codes 8015, 8140-8149, 8260-8490, 8560, and 8570-8575), and all histological types analyzed together (all ICD-O-3 codes for cervical cancer).

Age-adjusted and age-specific incidence rates were calculated by histological type. Incidence rates (per 100,000 women) were estimated using SEER*Stat software, v.6.5.5 (41), and adjusted to the 2000 PR Population data provided by the Census 2000 (US Census Bureau) (42). Differences in age distribution were assessed using chi-square (x2) statistics. Annual percent changes (APC) by histological type and age group (15-29, 30-44, 45-59, 60-74, and 75+) were estimated using the Joinpoint Regression Program, v.3.2 (43), to evaluate the incidence trends from 1987 to 2004. The parameters used in Joinpoint to estimate APCs were 1) log transformation of the rates, 2) two-joinpoint model, 3) standard errors of rate, 4) uncorrelated error model, 5) Hudson's method, and 6) permutation model selection methods.

Results

Study Population

A total of 3,516 invasive cervical cancer cases (diagnosed from 1987 until 2004) were included in the analysis. Three-fourths of the cases (76.3%) were SCC, 15.4% were ADC, and 8.3% had other histologies. The median age at diagnosis was 51 years, which was similar ([chi square] 1.78, p = 0.182) for SCC (52 years) and for ADC (50 years). Table 1 displays the distribution of cervical cancer cases by age group and histology. Overall, 173 (4.9%) of cases were below 30 years of age at diagnosis. Women aged 30 to 59 years contributed 60% of the total cases. There were no significant differences in the distribution of age at diagnosis by histology in the cervical cancer cases analyzed ([chi square] 7.37, p = 0.118).

Cervical cancer is a rare diagnosed in younger women in PR. Only 4.9% of cases were diagnosed in women aged under 30 years, most of these (3.4%) were diagnosed in women between the ages of 25 and 29 (Table 1). Figure 1 shows an upward trend in SCC diagnoses starting at age 20, plateauing at 45 to 55 years, and, after a dip, increasing smoothly thereafter. The age-specific incidence rates for ADC begin to rise slightly at age 25 and then remain relatively stable from 45 years onward.

Trends by Histologic Type and Age Group All Histological Types

Age-adjusted incidence rate for cervical carcinoma showed a downward trend (from 14.9 per 100,000 in 1987 to 10.6 per 100,000 women in 2004), with an APC of-2.1% (95% CI: -3.0%, -1.3%, p < 0.05) (Figure 2). When trends were stratified by age group, significant decreases in incidence were observed for the groups encompassing ages 45-59 (APC = -2.2%), 60-74 (APC = -5.3%), and 75+ (APC = -5.2%) years of age (Figures 3 and 4). However, women aged 30-44 years had a statistically significant increase of 1.4% (p < 0.05) annually, while women aged 15-29 had a similar increase of 1.4% (p > 0.05) but it was not statistically significant (Figure 4).

[FIGURE 1 OMITTED]

Squamous cell carcinoma (SCC)

The age-adjusted rates of SCC decreased from 12.3 to 7.8 per 100,000 women from 1987 to 2004 (Figure 2), with a decrease of 3.2% (95% IC: -3.9%, -2.5%, p < 0.05) annually. Since 76% of all invasive cervical cancer cases are SCC, the trends by age for SCC are similar to the trends for all histological types combined. However, for SCC the increased rate in women aged 30-44 years (APC = 0.4%) was not statistically significant, while women aged 15-29 years showed a non-significant reduction of 2.4% (p > 0.05) annually, contrary to the trend presented for all histological types analyzed together (Figure 4).

Adenocarcinoma (ADC)

An average of 30 cases of ADC is diagnosed annually in PR, thus the incidence rates were relatively low (ranging from 1.4 to 2.7 per 100,000 women/year) during the study period (Figure 2). AD C was less frequently diagnosed among women in PR; an increase of 0.8% (95% CI: -0.7%, 2.3%, p > 0.05) annually was observed. Trends of ADC by age group showed a statistically significant increase of 3.8% (95% CI: 0.9%, 6.8%, p < 0.05) annually for women aged 30-44 years, while for women aged 45-59 (APC = -0.4%) and 60-74 (APC = -2.5) years, a slight decrease in incidence was observed (Figure 4). For the youngest (15-29 years) and oldest age groups (75+ years), there were no ADC cases reported for various years; therefore, Joinpoint software could not estimate the APC.

[FIGURE 2 OMITTED]

[FIGURE 3 OMITTED]

[FIGURE 4 OMITTED]

Discussion

Over the past several decades, invasive cervical cancer incidence rates in PR have been steadily declining from 35.1 per 100,000 in 1950-54 to 8.8 per 100,000 women in 1985-89 (age adjusted to the 1970 population of PR) (4). Using cancer cases (1987-2004) from the PRCCR, our analysis showed a continuation of this trend for invasive cervical cancer and, in particular, for SCC. The decrease in overall incidence of cervical cancer principally reflects the decrease in the incidence of SCC occurring mainly in women aged 45 years or older. Nevertheless, the trend for ADC has remained stable for the same period. Similar to other populations, overall incidence trends for younger women (15-29 years) increased (10, 44-48). In this study a significant increase in ADC was seen in women aged 30-44 years of age.

Over the last decades, reproductive, lifestyle, and environmental risk factors, such as the decline in parity (49, 50), increased access to health care (51), the greater participation of women in the labor force, increased socioeconomic status and educational levels (14, 52, 53), and a decrease in tobacco use (51), have changed in PR. However, these changes could partially explain the reduction in the overall incidence rates of cervical cancer in PR. According to Grandes (5), multiple regression analysis reflected that the reduction in the rates of invasive cervical cancer in PR during 1963 to 1987 was due significantly (p = 0.0103) to the increase of the socioeconomic level and not by the screening program.

Some of the strongest identified risk factors for cervical cancer acting as cofactors to HPV are the long term use of oral contraception (22-24, 54, 55), high parity (24, 56, 57), and cigarette smoking (24, 28, 37). Recent epidemiological studies (22, 55) that evaluated the role of oral contraceptives in cervical cancer strongly suggest that women who used oral contraceptives had an increased risk of cervical cancer (up to twofold), but only those women who were both long-term users (>5 years) and who had persistent HPV infections of the cervix. The limited available data suggest that the relative risk of cervical cancer may decrease after the use of oral contraceptives ceases (22). However, only limited data are available regarding of oral contraceptive use in married Puerto Rican women aged 15-49 years; 21.5%, 14.7%, and 1.8% of married women of 15-24, 25-34 and 35-49 years of age, respectively, used oral contraceptives (58). The fact that scarce data exist on patterns of oral contraceptive use and HPV in a Puerto Rican population, limits us in hypothesizing about the impact of these factors on cervical cancer incidence trends.

A significant association between the number of full-term pregnancies and an increased risk of invasive cervical cancer, especially SCC cancer, has been reported (57). Multiple pregnancies may have a cumulative traumatic or immunosuppressive effect on the cervix, thereby facilitating the acquisition of HPV infection (59). Nonetheless, PR has experienced a reduction of fertility rates (49, 60), and the average number of children born of women of reproductive age (15-49 years) has decreased from 6.4 children in 1932 to 2.1 children in 1998 (49, 50). This suggests that a decline in parity could partly explain a reduction in cervical cancer but may in part contribute for the increased incidence trend of endometrial (61) and breast cancer (62, 63) observed in PR. The prevalence of hysterectomies in PR is high (13.1% for women 35 to 49 years and 32.5% for women [greater than or equal to] 50 years old), and this procedure provides the women who have it protection against developing cervical cancer (G. Ramos, et al, Estudio Continuo de Salud, unpublished data, 2002).

The carcinogenic effect of smoking tobacco and its role in cervical cancer was largely consistent with several studies that adjusted for HPV or restricted analyses to HPV-positive women (21, 28). According to BRFSS, the prevalence of tobacco use in PR has been in decline among women during the last decades (9.9% in 1996, 8.4% in 2004) (51), a risk factor associated mainly with SCC (20, 21, 25, 28). Lifestyle factors such as obesity and poor nutritional habits (especially the reduced consumption of fruits and vegetables) need also be considered, given that these factors have undergone drastic changes in PR (51).

Some Sexually Transmitted Diseases (STDs) such as Chlamydia trachomatis (30, 31, 33), Human Immunodeficiency Virus (HIV) (64) , Herpes Simplex Virus-2 (HSV-2) (65), and HPV infection, a major infectious etiological agent and risk factor for cervical cancer, are mainly acquired through sexual contact, which also increases the risk for cervical cancer. A possible mechanism whereby sexually transmitted infections could act is by inducing a local inflammatory response that could facilitate the establishment of a productive HPV infection (38). Transmission rates of Chlamydia infection in PR increased 88%, from 16.6 in 1993 to 92.7 per 100,000 persons in 2004, with the risk for women being more than 5-fold greater compared to that for men (66). These increases contrast the decreasing trend of SCC, where the effect of Chlamydia trachomatis appears to be more relevant for SCC than for ADC (31, 33). Moreover, PR is one of the top ten US states and territories with the highest cumulative number of HIV/AIDS cases (67). Given that cervical cancer is an important AIDS-defining malignancy (68), a significantly higher risk of cervical cancer has been observed in women with AIDS in PR, and that has not changed over time (69). This high risk of cervical cancer among women with AIDS in PR may contribute for the increasing trend observed among women aged 15-44 years, in whom HIV/AIDS is more prevalent. Even though the high risk of STDs such as Chlamydia infections and HIV, the high-risk sexual practice in early ages in younger cohorts (70-72), and the cofactors associated with HPV may contribute to the observed increased risk of cervical cancer among women aged 15-44 years in PR, there is no conclusive evidence to support that theory.

Widespread population-based screening programs for cervical cancer have been available in PR since 1961(3). One possible explanation for the decreasing temporal trends in SCC incidence rates and the contrary increase in those rates for ADC observed during the study period is that screening practices--especially the conventional Papanicolaou (Pap) test--are less effective at detecting ADC than they are at detecting SCC (73). The location of ADC can make detection by a Pap smear difficult because lesions develop in multiple locations in the cervix or in a high part of the endocervix and often go undetected (73). The absence of an overall trend in ADC incidence suggests that the screening program may have less impact for ADC (44). New and improved screening methods specifically directed at cytological changes in the endocervical glands are needed in order to more effectively detect pre-invasive and early invasive ADC (48, 73, 74). Nevertheless, it is important to note that in PR the overall decreasing trend of the risk of cervical cancer (which has so far been mainly SCC) was observed about 10 years before the introduction of Pap screening at the population level (4).

Our study shows an increased risk of cervical cancer among women of 15-29 and 30-44 years of age, particularly for ADC in women aged 30-44 years. Several authors have suggested possible explanations for the increasing trend of ADC in young women such, as the increase in the prevalence of persistent HPV infection and its cofactors (45-47, 75). The prevalence of HPV in PR has not been documented at the population level. However, such factors as high-risk sexual practices at an early age, having multiple sex partners, and lifetime number of partners--which factors are associated with HPV infection--have increased in younger cohorts (70-72). Also, the low prevalence of screening in younger women results in missing pre-invasive lesions, thereby limiting effectiveness in reducing the incidence rates in the younger age groups (48, 74). According to the Behavioral Risk Factor Surveillance System (BRFSS), women aged 18-24 years were less frequently screened than women aged 35 years or older (51). For the survey conducted from 1996 to 2004, in average, less than 42% of women 18-24 years of age in PR had a screening Pap test within the past three years as compared to over 70% for women aged 25 years or older. Also, Ortiz et al. (76) estimated the prevalence of women who, in 2006, reported having had a PAP test in the preceding 3 years as being 71.9% (95% CI: 69.4%-74.4%), below the recommended 90% established by Healthy People 2010.

One of the strengths of our study is the data provided by PRCCR, a population based-registry with high quality standard data. In 2003, a CDC audit concluded that 95.3% of all cancer cases diagnosed and treated in hospitals facilities in PR were accurately reported to the PRCCR; a result comparable to the US median (95%) (77). However, a limitation of our study is the lack of adjustment by hysterectomy rates, which deficiency may have resulted in an underestimation of disease occurrence (78). Also, the scarcity of invasive cervical cancer cases (particularly ADC) in women below 30 years resulted in less reliable rates. Given the small numbers observed annually for younger women, the precision of our rates is understandably low, which might lead to considerable variation in the rates. Therefore, the estimated APC incidence we report in this study reflects the relative change in what are, in absolute terms, small numbers (46). Caution is recommended in the interpretation of the clinical significance of these observed trends.

Although overall cervical cancer incidence has decreased over time, mainly due to the relatively greater reduction of SCC, ADC has not presented a similar decreasing trend. Also, our study identified an increased risk of invasive cervical cancer among women 15-44 years of age, in particular for AD C in women aged 30-44 years. The overall reduction of cervical cancer in PR may be attributable, in part, to an organized widespread screening program as well as lifestyle and environmental changes that have occurred over the last decades. However, the increased risk for ADC, particularly in younger women, suggests an argumentation of high-risk sexual practices, lower rates of appropriate screening and early detection of pre-invasive lesions, and the presence of high-risk HPV infection and its cofactors. The changing patterns of histology-specific cervical cancer incidence emphasize the importance of cancer surveillance by histopathology. The inclusion of HPV DNA tests in screening programs for high-risk women in PR would increase the detection rates of the precursors of cervical cancer for both SCC and ADC, as both histological types are associated with HPV. Future research should be undertaken over longer periods of time and should evaluate the potential risk cofactors associated with HPV, the introduction of the HPV vaccine, and the cost effectiveness of the HPV DNA testing in reducing cervical cancer incidence.

Acknowledgments

This work was supported in part by the Centers for Disease Control and Prevention-National Program of Cancer Registries [Grant #U58DP000782-01] for the Puerto Rico Central Cancer Registry. The authors have nothing to disclose with regard to this article.

References

(1.) Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin 2005 Mar-Apr;55:74-108.

(2.) GLOBOCAN 2002. Cancer Incidence, Mortality and Prevalence Worldwide [computer program]. Version 2.0. Lyon France: IARC Press 2004; 2010.

(3.) Martinez I. Changes of morbidity and mortality from cancer of the cervix uteri in Puerto Rico. Bol Asoc Med P R 1984;76:100-106.

(4.) Departamento de Salud de Puerto Rico. Informe Cancer de Puerto Rico 1991. Registro Central de Cancer de Puerto Rico; 1993.

(5.) Grandes G. Impacto del Programa de Deteccion Precoz sobre la incidencia y mortalidad por cancer invasivo escamoso de cerviz en Puerto Rico, 1969-1987 [master's thesis]. San Juan, PR; University of Puerto Rico, Medical Sciences Campus; 1990.

(6.) Karim-Kos HE, de Vries E, et. al. Recent trends of cancer in Europe: a combined approach of incidence, survival and mortality for 17 cancer sites since the 1990s. Eur J Cancer 2008;44:1345-1389.

(7.) Surveillance, Epidemiology, and EndResults (SEER) Program (www.seer.cancer.gov). SEER*Stat Database: Incidence - SEER 9 Regs Limited-Use, Nov 2006 Sub (1973-2004), National Cancer Institute, DCCPS, Surveillance Research Program, Cancer Statistics Branch, released April 2007, based on the November 2006 submission.

(8.) Ortiz AP, Soto-Salgado M, Calo WA, et al. Incidence and mortality rates of selected infection-related cancers in Puerto Rico and the United States. Infect Agent Cancer 2010;5:10.

(9.) Ronco G, Pilutti S, Patriarca S, et al. Impact of the introduction of organised screening for cervical cancer in Turin, Italy: cancer incidence by screening history 1992-98. Br J Cancer 2005;93:376-378.

(10.) Bray F, Loos AH, McCarron P, et al. Trends in cervical squamous cell carcinoma incidence in 13 European countries: changing risk and the effects of screening. Cancer Epidemiol Biomarkers Prev 2005;14:677-686.

(11.) Comber H, Gavin A. Recent trends in cervical cancer mortality in Britain and Ireland: the case for population-based cervical cancer screening. Br J Cancer 2004;91:1902-1904.

(12.) Quinn M, Babb P, Jones J, Allen E. Effect of screening on incidence of and mortality from cancer of cervix in England: evaluation based on routinely collected statistics. BMJ 1999;318:904-908.

(13.) IARC. Cervix cancer screening. IARC Handbooks of Cancer Prevention. Lyon, France: IARC Press; 2005.

(14.) Lopez de Munaim J. Epidemiologa descriptiva del cancer invasivo de cervix de Puerto Rico, 1963-1987 [master's thesis]. San Juan, PR; University of Puerto Rico, Medical Sciences Campus; 1990.

(15.) Drain PK, Holmes KK, Hughes JP, Koutsky LA. Determinants of cervical cancer rates in developing countries. Int J Cancer 2002;100:199-205.

(16.) Schiffman MH, Bauer HM, Hoover RN, et al. Epidemiologic evidence showing that human papillomavirus infection causes most cervical intra epithelial neoplasia. J Natl Cancer Inst 1993;85:958-964.

(17.) Walboomers JM, Jacobs MV, Manos MM, et al. Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J Pathol 1999;189:12-19.

(18.) Bosch FX, Lorincz A, Munoz N, Meijer CJ, Shah KV. The causal relation between human papillomavirus and cervical cancer. J Clin Pathol 2002;55:244-265.

(19.) Bosch FX, Manos MM, Munoz N, et al. Prevalence of human papillomavirus in cervical cancer: a worldwide perspective. International biological study on cervical cancer (IBSCC) Study Group. J Natl Cancer Inst 1995;87:796-802.

(20.) Castellsague X, Diaz M, de Sanjose S., et al. Worldwide human papillomavirus etiology of cervical adenocarcinoma and its cofactors: implications for screening and prevention. J Natl Cancer Inst 2006 Mar 1;98:303-315.

(21.) Appleby P, Beral V, Berrington de Gonzalez A., et al. Carcinoma of the cervix and tobacco smoking: collaborative reanalysis of individual data on 13,541 women with carcinoma of the cervix and 23,017 women without carcinoma of the cervix from 23 epidemiological studies. Int J Cancer 2006 Mar 15;118:1481-1495.

(22.) Smith JS, Green J, Berrington de Gonzalez A, et al. Cervical cancer and use of hormonal contraceptives: a systematic review. Lancet 2003 Apr 5;361:1159-1167.

(23.) Appleby P, Beral V, Berrington de Gonzalez A, et al. Cervical cancer and hormonal contraceptives: collaborative reanalysis of individual data for 16,573 women with cervical cancer and 35,509 women without cervical cancer from 24 epidemiological studies. Lancet 2007;370: 1609-1621.

(24.) Castellsague X, Munoz N. Chapter 3: Cofactors in human papillomavirus carcinogenesis--role of parity, oral contraceptives, and tobacco smoking. J Natl Cancer Inst Monogr 2003;20-28.

(25.) Berrington de Gonzalez A, Sweetland S, Green J. Comparison of risk factors for squamous cell and adenocarcinomas of the cervix: a meta-analy sis. Br J Cancer 2004;90:1787-1791.

(26.) Lacey JV, Jr., Swanson CA, Brinton LA, et al. Obesity as a potential risk factor for adenocarcinomas and squamous cell carcinomas of the uterine cervix. Cancer 2003;98:814-821.

(27.) Lacey JV, Jr., Brinton LA, Abbas FM, et al. Oral contraceptives as risk factors for cervical adenocarcinomas and squamous cell carcinomas. Cancer Epidemiol Biomarkers Prev 1999;8:1079-1085.

(28.) Plummer M, Herrero R, Franceschi S, et al. Smoking and cervical cancer: pooled analysis of the IARC multi-centric case--control study. Cancer Causes Control 2003;14:805-814.

(29.) Lacey JV, Jr., Brinton LA, Barnes WA, et al. Use of hormone replacement therapy and adenocarcinomas and squamous cell carcinomas of the uterine cervix. Gynecol Oncol 2000;77:149-154.

(30.) Smith JS, Bosetti C, Munoz N, et al. Chlamydia trachomatis and invasive cervical cancer: a pooled analysis of the IARC multicentric case-control study. Int J Cancer 2004;111:431-439.

(31.) Anttila T, Saikku P, Koskela P, et al. Serotypes of Chlamydia trachomatis and risk for development of cervical squamous cell carcinoma. JAMA 2001;285:47-51.

(32.) Madeleine MM, Anttila T, Schwartz SM, et al. Risk of cervical cancer associated with Chlamydia trachomatis antibodies by histology, HPV type and HPV cofactors. Int J Cancer 2007;120:650-655.

(33.) Koskela P, Anttila T, Bjorge T, et al. Chlamydia trachomatis infection as a risk factor for invasive cervical cancer. Int J Cancer 2000;85:35-39.

(34.) Lech MM, Ostrowska L. Risk of cancer development in relation to oral contraception. Eur J Contracept Reprod Health Care 2006;11:162-168.

(35.) dos Santos Silva I, Beral V. Socioeconomic differences in reproductive behaviour. IARC Sci Publ 1997;285-308.

(36.) Faggiano F, Partanen T, Kogevinas M, Boffetta P. Socioeconomic differences in cancer incidence and mortality. IARC Sci Publ 1997;65-176.

(37.) Winkelstein W, Jr. Smoking and cervical cancer--current status: a review. Am J Epidemiol 1990 Jun;131:945-957.

(38.) Franco EL, Schlecht NF, Saslow D. The epidemiology of cervical cancer. Cancer J 2003 Sep-Oct;9:348-359.

(39.) Puerto Rico Central Cancer Registry (PRCCR). Incidence Case File-Feb 2010. Comprehensive Cancer Center of University of Puerto Rico, 2010.

(40.) Fritz A, Jack A, Percy C, et al. International classification of diseases for oncology, 3rd ed. Geneva: World Health Organization; 2000.

(41.) SEER*Stat software (www.seer.cancer.gov/seerstat) version 6.5.2. [computer program]. Version 6.5.2 2010.

(42.) Junta de Planificacion, Programa de Planificacion Economica y Social, Oficina del Censo. Poblacion Estimada, Puerto Rico; 2000.

(43.) Joinpoint Regression Program [computer program]. Version 3.4.2. Bethesda, Md: National Cancer Institute, Division of Cancer Control and Population Sciences, Statistical Research and Applications Branch, 2002; 2010.

(44.) Bulk S, Visser O, Rozendaal L, et al. Cervical cancer in the Netherlands 1989-1998: Decrease of squamous cell carcinoma in older women, increase of adenocarcinoma in younger women. Int J Cancer 2005;113: 1005-1009.

(45.) Liu S, Semenciw R, Mao Y. Cervical cancer: the increasing incidence of adenocarcinoma and adenosquamous carcinoma in younger women. CMAJ 2001 Apr 17;164:1151-1152.

(46.) Chan PG, Sung HY, Sawaya GF. Changes in cervical cancer incidence after three decades of screening US women less than 30 years old. Obstet Gynecol 2003 Oct;102:765-773.

(47.) Bray F, Carstensen B, Moller H, et al. Incidence trends of adenocarcinoma of the cervix in 13 European countries. Cancer Epidemiol Biomarkers Prev 2005 Sep;14:2191-2199.

(48.) Smith HO, Tiffany MF, Qualls CR, Key CR. The rising incidence of adenocarcinoma relative to squamous cell carcinoma of the uterine cervix in the United States--a 24-year population-based study. Gynecol Oncol 2000 Aug;78:97-105.

(49.) Vazquez-Calzada J. La Poblacion de Puerto Rico y su Trayectoria Historica [The Population of Puerto Rico and its historic evolution]. Rio Pie dras, PR: Raga Offset Printing Service, 1988.

(50.) Pan American Health Organization: Special Program for Health Analysis Based on: World Population Prospects: the 1998 Revision United Nations. 1998.

(51.) Behavioral Risk Factor Surveillance System Survey Data [computer program]. Atlanta, Georgia: U.S: Department of Health and Human Services, Centers for Disease Control and Prevention; 1996-2004.

(52.) Rigau-Perez JG. Health in Puerto Rico in the 20th century [in Spansh]. P R Health Sci J 2000 Dec;19:357-368.

(53.) Negociado del Censo Federal. Censo de Poblacion y Vivienda de Puerto Rico: 1990 y 2000); Ano 1990, Compendio de Datos 3a y Ano 2000, Compendio de Datos3) y Junta de Planificacion, Programa de Planificacion Economica y Social, Oficina del Censo; 2000.

(54.) Moodley J. Combined oral contraceptives and cervical cancer. Curr Opin Obstet Gynecol 2004 Feb;16:27-29.

(55.) Moreno V, Bosch FX, Munoz N, et al. Effect of oral contraceptives on risk of cervical cancer in women with human papillomavirus infection: the IARC multicentric case-control study. Lancet 2002;359: 1085-1092.

(56.) Munoz N, Castellsague X, de Gonzalez AB, Gissmann L. Chapter 1: HPV in the etiology of human cancer. Vaccine 2006;24 Suppl 3:S3-1-S310.

(57.) Munoz N, Franceschi S, Bosetti C, et al. Role of parity and human papillomavirus in cervical cancer: the IARC multicentric case-control study. Lancet 2002 Mar 30;359:1093-1101.

(58.) Davila AL, Ramos G, Mattei H. Encuesta de Salud Reproductiva: Puerto Rico, 1995-1996. Resumen de los Hallazgos. [Reproductive Health Survey: Puerto Rico, 1995-1996:Summary Report]. San Juan, Puerto Rico: Escuela Graduada de Salud Publica; 1998.

(59.) Schneider A, Hotz M, Gissmann L. Increased prevalence of human papillomaviruses in the lower genital tract of pregnant women. Int J Cancer 1987 Aug 15;40:198-201.

(60.) Puerto Rico Department of Health,Axillary Secretariat for Planning and Development, Division of Statistical Analysis. Informe Anual de Estadisticas de Puerto Rico, 2003: Table 11-Specific Fertility Rates. San Juan, Puerto Rico.

(61.) Ortiz AP, Perez J, Otero-Dominguez Y, et al. Endometrial cancer in Puerto Rico: incidence, mortality and survival (1992-2003). BMC Cancer 2010;10:31.

(62.) Nazario CM, Figueroa-Valles N, Rosario RV. Breast cancer patterns and lifetime risk of developing breast cancer among Puerto Rican females. P R Health Sci J 2000 Mar;19:7-13.

(63.) Ortiz-Ortiz KJ, Figueroa-Valles NR, Perez-Irizarry J, et al. Patrones de incidencia y Mortalidad de Cancer de Mama en Puerto Rico. Revista Puertorriquena de Medicina y Salud Publica 2009;15:19-27.

(64.) Palefsky JM, Minkoff H, Kalish LA, et al. Cervicovaginal human papillomavirus infection in human immunodeficiency virus-1 (HIV)-positive and high-risk HIV-negative women. J Natl Cancer Inst 1999;91:226-236.

(65.) Smith JS, Herrero R, Bosetti C, et al. Herpes simplex virus-2 as a human papillomavirus cofactor in the etiology of invasive cervical cancer. J Natl Cancer Inst 2002 Nov 6;94:1604-1613.

(66.) Departamento de Salud de Puerto Rico. Programa de Prevencion de ETS/VIH/SIDA. 2005.

(67.) CDC. HIV/AIDS among Hispanics. National Center for HIV, STD, and TB Prevention, Divisions of HIV/AIDS prevention.11-16-2004, 2-7. 2005.

(68.) Maiman M, Fruchter RG, Clark M, et al. Cervical cancer as an AIDS defining illness. Obstet Gynecol 1997 Jan;89:76-80.

(69.) Ramirez-Marrero FA, Smith E, De La Torre-Feliciano T, et al. Risk of cancer among Hispanics with AIDS compared with the general population in Puerto Rico: 1987- 2003. P R Health Sci J 2010;3:29.

(70.) Mosher WD, Chandra A, Jones J. Sexual behavior and selected health measures: men and women 15-44 years of age, United States, 2002. Adv Data 2005 Sep 15;1-55.

(71.) Finer LB, Darroch JE, Singh S. Sexual partnership patterns as a behavioral risk factor for sexually transmitted diseases. Fam Plann Perspect 1999 Sep-Oct;31:228-236.

(72.) National Center for Chronic Disease Prevention and Health Promotion, Division of Adolescent and School Health. Youth Risk Behavior System Surveillance Data. Atlanta, Georgia: U.S: Department of Health and Human Services, Centers for Disease Control and Prevention, 2008.

(73.) Kalir T, Simsir A, Demopoulos HB, Demopoulos RI. Obstacles to the early detection of endocervical adenocarcinoma. Int J Gynecol Pathol 2005 Oct;24:399-403.

(74.) Zappa M, Visioli CB, Ciatto S, et al. Lower protection of cytological screening for adenocarcinomas and shorter protection for younger women: the results of a case-control study in Florence. Br J Cancer 2004;90:1784-1786.

(75.) Wu X, Groves FD, McLaughlin CC, et al. Cancer incidence patterns among adolescents and young adults in the United States. Cancer Causes Control 2005 Apr;16:309-320.

(76.) Ortiz AP, Hebl S, Serrano R, et al. Factors associated with cervical cancer screening in Puerto Rico. Prev Chronic Dis 2010 May;7:A58.

(77.) National Program of Cancer Registries: Technical Assistance and Audit Puerto Rico Central Cancer Registry, Case Completeness and Data Quality Audit. Atlanta, Georgia: Centers for Disease Control and Prevention; 2003.

(78.) Luoto R, Raitanen J, Pukkala E, Anttila A. Effect of hysterectomy on incidence trends of endometrial and cervical cancer in Finland 1953-2010. Br J Cancer 2004 May 4;90:1756-1759.

Javier Perez-Irizarry, MPH, CTR *; Cruz M. Nazario-Delgado, PhD ([dagger]); Taina De la Torre, MS, CTR *; Karen J. Ortiz-Ortiz, MPH, CTR *; Mariela Torres-Cintron, MS, CTR *; Nayda R. Figueroa-Valles, MD, MPH, CTR *

* Puerto Rico Central Cancer Registry, Cancer Control and Population Sciences Program, University of Puerto Rico Comprehensive Cancer Center, San Juan, Puerto Rico; ([dagger]) Graduate School of Public Health, Department of Biostatistics and Epidemiology, Medical Sciences Campus, University of Puerto Rico.

Author correspondence to: Nayda Figueroa-Valles, MD, MPH, CTR University of Puerto Rico Comprehensive Cancer Center, PMB 711, 89 De Diego Ave., Suite 105, San Juan, PR 00927-6346. Tel: (787) 772-8300 * Fax: (787) 752-3283 * Email: nfigueroa@rcpr.org
Table 1. Distribution of invasive cervical cancer cases by age group
in Puerto Rico, 1987-2004 ([dagger])

Age       SCC          ADC          Total
(years)   n (%)        n (%)        n (%)

15-29     121 (4.5)    17 (3.1)     173 (4.9)
30-44     800 (29.8)   183 (33.9)   1082 (30.8)
45-59     806 (30.0)   169 (31.3)   1028 (29.2)
60-74     628 (23.4)   118 (21.9)   814 (23.2)
75+       329 (12.3)   53 (9.8)     419 (11.9)
Total     2,684        540          3,516

([dagger])SCC = squamous cell carcinoma; ADC = adenocarcinoma
Gale Copyright: Copyright 2010 Gale, Cengage Learning. All rights reserved.