Background : Cervical cancer is the main cause of cancer deaths in some developing countries. Age-related cervical cancer incidence has been fundamental for understanding the different stages of carcinogenesis concepts. No Brazilian study explored the environmental risk factors involved on cervical cancer, according to age groups taking 70’s sexual revolution in Brazil as reference. Aim : To determine the prevalence of epidemiological and clinical aspects related to cervical cancer development in a sample of three age groups of Brazilian women based on 70’s sexual revolution. Methods : A cross-section study was proceeded in a hospital-based cohort of women with altered Pap-test refereed to the National Cancer Institute for Colposcopy and treatment from October 2004 to May 2006. Two register nurses interviewed all patients ascertaining risk factors and clinical characteristics. Biopsy, partial ablation were used for CIN-1, and conization was the treatment for CIN-2/3. Results : From 318 women included in the study, 42.8% were 18 - 30 years old (born after 1975), 43.4% were 31 - 49 years old (born 1955-1975), and 13.8% were 50 - 68 years old (born 1936-1954). Pregnancies (OR = 1.16; CI95%: 1.01 - 1.34) and menarche under 12 years old (OR = 1.95; CI95%: 1.17 - 3.25) were independently associated to CIN2- 3/cancer in 18 - 30 age group; menopause age (OR = 1.21; CI95%: 1.04 - 1.41) and current smoking habit (OR = 1.37; CI95%: 1.10 - 1.70) were associated to CIN2- 3/cancer in 31 - 49 age group; no statistical significance was observed for 50 - 68 age group. Conclusion : Brazilian women present distinct risk for cervical cancer according to the generation they belong, when taking the Brazilian sexual revolution on 70’s as a reference.
Cervical cancer is the second major cause of cancer deaths among women worldwide, and is still the main cause of cancer deaths in some developing countries [
Age-related incidence has been fundamental for understanding the different stages of carcinogenesis concepts [
However, the reason for this exponential increase in the cervical cancer rates among young women in 70s and 80s is still unknown. Although there is evidence of a change in the screened population over time from younger to older women, it provides a partial explanation for these age-specific trends in cervical cancer mortality [
In Brazil, it has been reported a high prevalence of high-risk HPV―16 (49.2%), 58 (13.4%), 31 (11.2%)―among all levels of lesions, and an increasing tobacco smoking prevalence among women under 18 years old [
Thus, the purpose of this study was to determine the prevalence of epidemiological and clinical aspects related to cervical cancer development in a sample of three age groups of Brazilian women based on 70’s sexual revolution, seeking possible specific co-factors associated with this neoplasia. As a whole, this study aimed to explore the sexual pattern modifications observed among women in Brazil, trying to elucidate their possible role in cervical cancer pathogenesis experienced in such population.
All cervical cytological and histological diagnosis and cervical cancer treatment are carried out at Hospital of Cancer II of Brazilian National Cancer Institute, wherein this investigation was performed using available recorded data. These data enabled the establishment of three different age groups of women as follow: women had born between the years 1976-88; women born between the years 1956-75; and those born between 1937-55. Therefore, considering 1970 as the year of the significant turning point of sexual behavior in Brazil, the studied population was comprised of women who were 18 - 30 years old, 31 - 49 years old, and 50 - 70 years old at the time of the interview from October 2004 to May 2006.
Patients were eligible if they were older than 18 years old, had not undergone any cervical treatment in the past 6 months, were free of any psychiatric disease, were either literate or brought a literate relative to witness the informed consent explanation. Women who refused to sign the informed consent or were left untreated because they had no lesion at the time of the colposcopy test were excluded from this study.
All enrolled patients signed the informed consent before being interviewed to ascertain exposures to risk factors and clinical characteristics, following the colposcopy test. Biopsy, partial ablation with diathermy and electrocauterization were used for CIN-1, and conization was the treatment of choice for CIN-2/3. Present study was approved by the Ethical Committee of both, National Cancer Institute in Brazil and the National School of Public Health, Oswaldo Cruz Foundation.
Considering the cervical lesions prevalence in the State of Rio de Janeiro in 2002 (56.5% of CIN I, 21.4% of CIN II, 15.12% of CIN III, 2.8% of squamous cancer, 0.33% of adenocarcinoma in situ, and 0.82% of invasive adenocarcinoma) and a difference of 5% - 15% of each lesion degree prevalence as the worse expected value, a survey including samples of 42 women with CIN-1, 61 women with CIN-2, 49 with CIN-3, and 113 with cervical cancer were required to obtain statistically significant estimates (error I = 0.05; power = 80%) in the studied population.
After signing an informed consent and answering the questionnaire, patients underwent washing of the cervix and lower genital tract with 4% - 6% acetic acid solution, and visual inspection under colposcopy. Colposcopy impressions, lesion size and suspected grade were reported. Biopsies were made of suspicious lesions; and a Pap smear test was carried out if the colposcopy evaluation was unsatisfactory. When the result of the Pap exam at the time of colposcopy was altered, endocervical curettage (ECC) was performed.
Histological diagnosis was made through slides stained with hematoxylin and eosin(HE) for grading of the cervical lesion according to the Bethesda System [
Two oncology gynecology surgeons performed the colposcopic exams and Pap smear tests. Histological and cytological specimens were evaluated at the Department of Pathology, Brazilian National Cancer Institute.
Age, self reported skin color, education level, age at menarche, age at first sexual intercourse, parity, number of abortions, menopausal status, number of sexual partners, Marital status (if live in the same house with a sexual partner or not), history of sexually transmitted diseases (STD), contraceptive method use, co-morbidity diseases history (diabetes mellitus, hypertension), HIV status (yes/no), HBS-Ag (yes/no), HCV (yes/ no), smoking status (current, former, and never smoking) and previous Pap smear tests were obtained from an interview-administered questionnaire. Region of birth was also collected, since this variable may reflect cultural differences in sexual behavior related to different regions of Brazil (e.g. women born in Northeast region at 1937-55, could be more conservative than those who had born in Southeast in the same years). All patients were interviewed by two trained nurses applying standardized procedures.
Tobacco consumption was classified as never smoked, no passive smoking; former smoker, and current smoker. Smoking habit variables were defined as the cumulative exposure of daily cigarette packs smoked, expressed as pack-year. For this analysis, we considered 1 g of tobacco for 1 cigarette, 4 cigarettes for each cigar, and 3 cigarettes for each pipe [
Comparisons between frequencies among age groups were performed using Chi-Square test, and variables expressed as means were evaluated using independent Student’s t-test. Mantel-Haentszel procedures were performed for trend analysis between the age groups. Significant level considered in each analysis was 5%.
Association between CIN 2-3/cancer and selected risk factors at the diagnosis was first ascertained using a cross-sectional approach. Odds ratios (OR) and their 95% confidence intervals were obtained to evaluate the magnitude of association between CIN 2-3/cancer development and risk factors, using a bivariate analysis. Multivariate analysis was accomplished to obtain adjusted OR using logistic regression analysis (CI: 95%). Associations between each variable and disease susceptibility (negative/CIN-1 vs. CIN 2-3/Cancer) were adjusted by age at first sexual intercourse, pack-year smoked (when indicated), number of sexual partners and contraceptive use. Age at menopause, number of pregnancy and pack-year smoked were evaluated as continuous variables.
All analyses were proceeded using STATA program (5.0 version, Stata Press, College Station, TX).
From October 2004 to May 2006, 463 women met the inclusion criteria and 18 patients (3.9%) refused to participate. From 445 patients who agreed to sign the informed consent, 318 patients (71.5%) were submitted to the lesion excision or biopsy (
Variables | N* | % | IC (95%) |
---|---|---|---|
Total | 318 | 100.00 | |
Age (Years) | |||
18 - 30 | 136 | 42.8 | (37.3 - 48.2) |
31 - 49 | 138 | 43.4 | (37.9 - 48.8) |
50 - 68 | 44 | 13.8 | (10.0 - 17.6) |
Birth Region State of Rio de Janeiro Other southeast/South states North/Northeast side | 207 36 75 | 65.1 11.3 23.6 | (59.9 - 70.3) (7.8 - 14.8) (18.9 - 28.3) |
Occupation House wife House keeper Unskilled worker Student Others | 98 71 15 15 119 | 30.9 22.4 4.8 4.8 37.5 | (25.7 - 35.9) (17.7 - 26.9) (2.4 - 7.0) (2.4 - 7.0) (32.1 - 42.7) |
Ethnicity White Black Multiethnic | 95 64 159 | 29.9 20.1 50.0 | (24.8 - 34.9) (15.7 - 24.5) (44.5 - 55.5) |
Education Level Incomplete Elementary school Complete Elementary/Middle school Complete High School Complete/incomplete College Degree | 167 85 53 13 | 52.6 26.8 16.7 4.1 | (47.0 - 58.0) (21.9 - 31.6) (12.6 - 20.8) (1.9 - 6.3) |
Marital Status with no partner with a partner | 104 214 | 32.7 67.3 | (27.5 - 37.9) (62.1 - 72.5) |
Reference Cytology CIN 1 CIN 2 CIN 3 ASCUS/AGUS Invasive cancer/Adenocarcinoma | 16 132 112 50 8 | 5.1 41.5 35.3 15.8 2.6 | (2.6 - 7.4) (36.1 - 46.9) (30.0 - 40.5) (11.7 - 19.7) (0.8 - 4.2) |
HIV Yes No | 6 312 | 1.9 98.1 | (0.4 - 3.4) (96.6 - 99.6) |
HCV Yes No | 10 304 | 3.2 96.9 | (1.2 - 5.1) (93.3 - 97.9) |
HBS-Ag Yes No | 23 291 | 7.3 92.7 | (4.4 - 10.1) (88.4 - 94.6) |
Diabetes Mellitus Yes No | 12 306 | 3.8 96.2 | (1.7 - 5.9) (91.4 - 98.3) |
Hypertension Yes No | 47 271 | 14.8 85.2 | (10.9 - 18.7) (81.3 - 89.1) |
*Totals may change according to missing values.
and 127 (28.5%) were left untreated because they had no visible lesion at the colposcopy test and presented no changes at the Pap smear test taken at the time of colposcopy exam.
Demographic and clinical characteristics of enrolled women are presented at
Crude and adjusted odds ratio (OR) for CIN 2-3/cancer development, according to age group, are presented in
Observed increase in the incidence of adenocarcinoma and adenosquamous carcinoma since the early 1970s has been attributed to the sexual revolution in the late 1960s [
Variables | 18 - 30 years old N = 136 | 31 - 49 years old N = 138 | 50 - 68 years old N = 44 | ||||
---|---|---|---|---|---|---|---|
N (%) | 95% CI | N (%) | 95% CI | N (%) | 95% CI | p-trend | |
Birth region State of Rio de Janeiro Southeast/South states North/Northeast side | 104 (76.5)*φ 12 (8.8)φ 20 (14.7)*φ | (69.3 - 83.6) (4.1 - 13.6) (8.8 - 20.7) | 87 (63.0)*π 13 (9.4) 37 (26.8)π | (55.0 - 71.1) (5.1 - 15.2) (19.4 - 34.2) | 16(36.4)φπ 10 (22.7)φ 18 (40.9)φ | (2.21 - 50.6) (10.3 - 35.1) (26.4 - 55.4) | P = 0.0000 P = 0.0360 P = 0.0002 |
Occupation House wife House keeper Unskilled worker Student Others | 48 (35.3) 19 (14.0)*φ 06 (4.4) 14 (10.3) 49 (36.0) | (27.3 - 43.3) (8.1 - 19.8) (1.0 - 7.9) (5.2 - 15.4) (28.0 - 44.1) | 38 (27.5) 39 (28.3)* 08 (5.8) 0 (0.0) 53 (38.4) | (20.1 - 35.0) (20.7 - 35.8) (1.9 - 9.7) - (30.3 - 46.5) | 12 (27.3) 13 (29.5)φ 01 (2.3) 01 (2.3) 17 (38.6) | (14.1 - 40.4) (16.1 - 43.0) - - (24.2 - 53.0) | P = 0.2062 P = 0.0048 P = 0.8014 P = 0.0010 P = 0.6854 |
Ethnicity White Black Multiethnic | 46 (33.8) 30 (22.1) 60 (44.1)φ | (28.0 - 44.1) (15.1 - 29.0) (35.8 - 52.5) | 33 (23.91) 26 (18.84) 79 (57.25)* | (16.8 - 31.0) (12.3 - 25.4) (49.0 - 65.5) | 16 (36.4) 08 (18.2) 20 (45.4) | (22.1 - 50.6) (6.8 - 29.6) (30.7 - 60.2) | P= 0.6572 P = 0.4829 P = 0.3329 |
Education Level Incomplete Elementary school Complete Elementary/Middle school Complete High School Complete/incomplete College Degree | 53 (39.0)*φ 50 (36.8)φ 27 (19.8) 06 (4.4) | (30.8 - 47.2) (28.7 - 44.9) (13.1 - 26.6) (1.0 - 7.9) | 79 (57.1)*π 31 (22.4)* 22 (15.9) 06 (4.3) | (49.0 - 65.5) (15.5 - 29.4) (9.8 - 22.0) (0.9 - 7.8) | 35(79.5)φπ 04 (9.1) 04 (9.1) 01 (2.3) | (67.6 - 91.5) - - - | P = 0.0000 P = 0.0001 P = 0.0967 P = 0.6134 |
Marital Status with no partner with a partner | 48 (35.3) 88 (64.7) | (27.3 - 43.3) (56.7 - 72.7) | 44 (31.9) 94 (68.1) | (24.1 - 39.7) (60.3 - 75.9) | 12 (27.3) 32 (72.7) | (14.1 - 40.4) (62.2 - 87.8) | P = 0.3089 |
Reference Cytology CIN-1 CIN-2/3 Ascus/Agus Câncer | 12 (8.8) 107 (78.7)φ 17 (12.5)φ 0 (0.0) | (4.1 - 13.6) (71.8 - 85.6) (6.9 - 18.1) - | 4 (2.9) 106 (76.8)π 23 (16.7)π 03 (2.2) | - (69.8 - 83.9) (10.4 - 22.9) - | 0 (0.0) 08(18.2)φπ 33(75.0)φπ 03 (6.8) | - (6.8 - 29.6) (62.2 - 87.8) - | P = 0.0065 P = 0.0000 P = 0.0000 P = 0.0120 |
Histological results Negative CIN-1 CIN-2/3 Cancer | 20 (14.7)*φ 35 (25.7)* 76 (55.9) 05 (03.7) * | (8.8 - 20.7) (18.4 - 33.1) (46.8 - 63.5) (1.0 - 7.9) | 37 (26.8)* 19 (13.8)* 67 (48.5) 15 (10.9)* | (19.4 - 34.2) (8.0 - 19.5) (40.2 - 56.9) (5.7 - 16.1) | 17(38.6)φ 03 (6.8) 18 (40.9) 06 (13.6) | (24.2 - 53.0) - (26.4 - 55.4) (3.5 - 23.8) | P = 0.0004 P = 0.0011 P = 0.0024 P = 0.0120 |
Diabetes Mellitus Yes No | 0 (0.0) 136 (100) | - | 05 (3.6) 133 (96.4) | - - | 07 (15.9) 37 (84.1) | (5.1 - 26.7) (73.3 - 94.9) | P = 0.0000 |
Hypertension Yes No | 3 (2.2) 133 (97.8) | - | 23 (16.7)π 115 (83.3)π | (10.4 - 22.9) (77.1 - 89.6) | 21 (47.7)π 23 (52.3)π | (33.0 - 62.5) (37.5 - 67.0) | P = 0.0000 |
*p ≤ 0.05 (Between 18 - 30 years vs 31 - 49 years old);φ p ≤ 0.05 (Between 18 - 30 years vs. 50 - 68 years old); π p ≤ 0.05 (Between 31 - 49 years old vs. 50 - 68 years old).
Variables | 18 - 30 years old N = 136 | 31 - 49 years old N = 138 | 50 - 68 years old N = 44 | |||
---|---|---|---|---|---|---|
Normal/CIN-1 (n = 55) | CIN 2-3/Cancer (n = 81) | Normal/CIN-1 (n = 56) | CIN 2-3/Cancer (n = 82) | Normal/CIN-1 (n = 20) | CIN 2-3/Cancer (n = 24) | |
Menopause (Mean ± SD) | - | - | 46.7 (0.6)* | 42.5 (0.7)* | 46.5 (7.5)* | 50.0 (2.8)* |
Number Pregnancies (Mean ± SD) | 1.6 (1.5)* | 2.3 (1.5)* | 3.2 (2.0) | 3.7 (2.2) | 4.1 (2.1) | 4.2 (3.1) |
Pack-year smoked (Mean ± SD) | 3.4 (4.5) | 5.9 (6.7) | 12.0 (10.6)* | 19.2 (15.9)* | 33.0 (41.5) | 22.0 (26.0) |
Menarche | ||||||
≤12 years | 28 (50.9) | 50 (61.7) | 39 (69.6) | 52 (63.4) | 12 (60.0) | 14 (58.3) |
>12 years | 27 (49.1) | 31 (38.3) | 17 (30.4) | 30 (36.6) | 08 (40.0) | 10 (41.7) |
Age at sexual onset | ||||||
≤16 years | 35 (63.6) | 61 (75.3) | 15 (26.8)* | 39 (47.6)* | 05 (25.0) | 07 (29.2) |
>16 years | 20 (36.4) | 20 (24.7) | 41 (73.2) | 43 (52.4) | 15 (75.0) | 17 (70.8) |
Parity | ||||||
0 - 1 | 39 (70.9) | 39 (48.1) | 16 (28.6) | 16 (19.5) | 02 (10.0) | 06 (25.0) |
>1 | 16 (29.1)* | 42 (51.9)* | 40 (71.4) | 66 (80.5) | 18 (90.0) | 18 (75.0) |
Number of Abortions | ||||||
0 - 1 | 49 (89.1) | 72 (88.9) | 47 (83.9) | 64 (78.0) | 14 (70.0) | 14 (58.3) |
>1 | 06 (10.9) | 09 (11.1) | 9 (16.1) | 18 (22.0) | 06 (30.0) | 10 (41.7) |
Number of Sexual Partners | ||||||
1 - 2 | 21 (38.2) | 25 (30.9) | 21 (37.5) | 15 (18.3) | 11 (55.0) | 09 (37.5) |
3 - 4 | 16 (29.1) | 29 (35.8) | 13 (23.2)* | 33 (40.2)* | 03 (15.0) | 10 (41.7) |
≥5 | 18 (32.7) | 27 (33.3) | 22 (39.3)* | 34 (60.7)* | 06 (30.0) | 05 (20.8) |
Oral Contraceptive | ||||||
Current use | 38 (69.1) | 57 (70.4) | 29 (51.8) | 42 (51.2) | 6 (30.0)* | 13 (54.2)* |
Former use | 07 (12.7) | 17 (21.0) | 17 (30.3) | 27 (32.9) | 9 (45.0) | 4 (16.7) |
Never use | 10 (18.2) | 07 (8.6) | 10 (17.9) | 13 (15.9) | 5 (25.0) | 7 (29.2) |
Duration of contraceptive use | ||||||
0 | 10 (18.2) | 07 (8.6) | 11 (19.6) | 14 (17.1) | 05 (25.0) | 07 (29.2) |
1 - 60 | 28 (50.9) | 38 (47.0) | 16 (28.6) | 31 (37.8) | 06 (30.0) | 08 (33.3) |
≥60 | 17 (30.9)* | 36 (44.4)* | 29 (51.8) | 37 (45.1) | 09 (45.0) | 09 (37.5) |
Tobacco Smoking | ||||||
Current smoker | 10 (18.2) | 20 (24.7) | 14 (25.0)* | 39 (47.6)* | 4 (20.0) | 8 (34.8) |
Former smoker | 04 (7.3) | 14 (17.3) | 13 (31.2) | 18 (22.0) | 9 (45.0) | 8 (34.8) |
Never smoke | 41 (74.5) | 47 (58.0) | 29 (51.8) | 25 (30.5) | 7 (35.0) | 7 (30.4) |
Duration of tobacco smoking | ||||||
≤15 | 14 (100) | 30 (88.2) | 10 (37.0) | 11 (19.3) | 04 (30.8) | 06 (37.5) |
>15 | 0 (0.0) | 04 (11.8) | 17 (63.0) | 46 (80.7) | 09 (69.2) | 10 (62.5) |
*p ≤ 0.05 (between groups: Negative/LSIL vs. HSIL/Cancer.
Variables | 18 - 30 years old | 31 - 49 years old | 50 - 68 years old | |||
---|---|---|---|---|---|---|
crudeOR (CI:95%) | *adj. OR (CI:95%) | crude OR (CI:95%) | *adj. OR (CI:95%) | crude OR (CI:95%) | *adj. OR (CI:95%) | |
Menopause age | - | - | 0.44 (0.25 - 0.76) | 1.21 (1.04 - 1.41) | 1.08 (0.99 - 1.18) | 1.13 (0.98 - 1.32) |
Number Pregnancy | 1.10 (1.02 - 1.20) | 1.16 (1.01 - 1.34) | 1.04 (0.98 - 1.11) | 1.03 (0.98 - 1.09) | 1.01 (0.91 - 1.11) | 1.03 (0.89 - 1.20) |
Pack-year smoked | 1.02 (0.99 - 1.04) | 1.02 (0.99 - 1.05) | 1.01 (1.00 - 1.019) | 1.00 (0.99 - 1.01) | 0.99 (1.00 - 1.01) | 0.99 (0.98 - 1.01) |
Menarche | ||||||
>12 years | 1.00 | 1.00 | 1.00 | 1.00 | 1.00 | 1.00 |
≤12 years | 1.03 (0.85 - 1.25) | 1.95 (1.17 - 3.25) | 1.12 (0.84 - 1.49) | 1.22 (0.94 - 1.57) | 1.03 (0.59 - 1.81) | 0.89 (0.38 - 2.09) |
Age at sexual onset | ||||||
>16 years | 1.00 | 1 | 1 | 1 | 1 | 1 |
≤16 years | 1.27 (0.92 - 1.76) | 1.06 (0.65 - 1.73) | 1.41 (1.07 - 1.86) | 1.20 (0.95 - 1.51) | 1.10 (0.60 - 2.01) | 0.81 (0.35 - 1.87) |
Parity | ||||||
0 - 1 | 1 | 1 | 1 | 1 | 1 | 1 |
>1 | 1.45 (1.09 - 1.91) | 1.26 (0.82 - 1.91) | 1.24 (0.88 - 1.77) | 1.02 (0.78 - 1.32) | 0.67 (0.35 - 1.26) | 0.65 (0.23 - 1.80) |
Number of Abortions | ||||||
0 - 1 | 1 | 1 | 1 | 1 | 1 | 1 |
>1 | 1.01 (0.65 - 1.57) | 1.43 (0.80 - 2.59) | 1.16 (0.83 - 1.62) | 1.26 (0.97 - 1.65) | 1.25 (0.71 - 2.19) | 1.44 (0.58 - 3.59) |
Number of Sexual Partners | ||||||
1 - 2 | 1 | 1 | 1 | 1 | 1 | 1 |
3 - 4 | 1.18 (0.84 - 1.67) | 0.67 (0.39 - 1.17) | 1.72 (1.16 - 2.55) | 1.09 (0.81 - 1.48) | 1.71 (0.91 - 3.21) | 1.41 (0.57 - 3.49) |
≥5 | 1.10 (0.78 - 1.57) | 0.91 (0.57 - 1.44) | 1.46 (0.98 - 2.15) | 1.05 (0.79 - 1.41) | 1.01 (0.47 - 2.17) | 0.89 (0.31 - 2.49) |
Oral Contraceptive | ||||||
Never use | 1 | 1 | 1 | 1 | 1 | 1 |
Former use | 1.72 (0.98 - 3.03) | 1.11 (0.64 - 1.83) | 1.08 (0.71 - 1.66) | 0.89 (0.64 - 1.24) | 0.53 (0.22 - 1.24) | 0.42 (0.13 - 1.36) |
Current use | 1.46 (0.88 - 2.41) | 1.08 (0.57 - 0.44) | 1.05 (0.70 - 1.56) | 0.93 (0.70 - 1.24) | 1.17 (0.62 - 2.23) | 1.15 (0.44 - 2.99) |
Duration of contraceptive use | ||||||
0 | 1 | 1 | 1 | 1 | 1 | 1 |
1 - 60 months | 1.40 (0.83 - 2.35) | 0.99 (0.57 - 1.73) | 1.18 (0.78 - 1.77) | 0.90 (0.67 - 1.22) | 0.98 (0.48 - 1.99) | 0.77 (0.27 - 2.21) |
≥60 months | 1.65 (0.98 - 2.78) | 1.22 (0.69 - 2.18) | 1.00 (0.67 - 1.49) | 0.93 (0.69 - 1.27) | 0.86 (0.43 - 1.71) | 0.82 (0.29 - 2.32) |
Tobacco Smoking | ||||||
Never smoke | 1 | 1 | 1 | 1 | 1 | 1 |
Former smoker | 1.46 (0.99 - 2.14) | 1.44 (0.97 - 2.13) | 1.25 (0.85 - 1.85) | 1.20 (0.94 - 1.54) | 0.94 (0.46 - 1.93) | 1.20 (0.54 - 2.65) |
Current smoker | 1.25 (0.89 - 1.75) | 1.31 (0.93 - 1.87) | 1.59 (1.15 - 2.20) | 1.37 (1.10 - 1.70) | 1.33 (0.65 - 2.73) | 1.19 (0.55 - 2.60) |
Duration of tobacco smoking | ||||||
≤15 years | 1 | 1 | 1 | 1 | 1 | 1 |
>15 years | 1.47 (0.82 - 2.61) | 1.43 (0.76 - 2.72) | 1.39 (0.96 - 2.03) | 1.13 (0.90 - 1.43) | 0.88 (0.43 - 1.77) | 0.74 (0.35 - 1.60) |
*Odds Ratio adjusted by Number of Sexual Partners, Contraceptive use, Age at sexual onset and Pack-year smoked.
havior, and habits of women who were at age of 15 - 30, under 15, and those who were born on an already changed society. Such sexual changing could modulate the risk of acquitting HPV infection between age groups, leading to a different pattern of co-factors distribution and different risk of CIN 2-3/cancer according to age groups [
In the present study, we observed a smaller contribution of affected women born on 1937-1955 years (13.8%) as compared to those born on 1956-75 and 1976-88, respectively, 43.4% and 42.8%. Until 1998 cervical cancer screening in Brazil was opportunistic, and only after 1998 screening for cervical cancer has been mainly strengthened as a systematical program. So, our results could be explained by the low Pap test coverage of the 50 - 70 years old group. Also, it could result from different reasons, such as behavioral differences among generations to undergo the Pap exam, as a consequence of their poorer survival after diagnosis by the screened women, or lower incidence of precursor lesion among the oldest women [
The varying development of cervical cancer according to age groups because of behavioral, cultural, social and educational differences is highlighted by the observation that 40.9% of women from the oldest group, compared to 14.7% among the youngest, were migrants and showed lower education.
As expected, CIN-1 was statistically more frequent (25.7%) and cancer was statistically less frequent (03.7%), among the youngest women, as compared to the oldest women (6.8% and 13.3%, respectively). Nevertheless, considering the latency needed to develop CIN 2-3, a higher frequency of these lesions would be expected among older women. Thus, unexpectedly, a higher frequency of CIN 2-3 (55.9%) was only seen in the youngest women as compared to the older women (CIN 2-3 1956-75: 48.6%; CIN 2-3 1937-55: 40.9%), with a significant linear trend between them (p-trend = 0.0024).
Epidemiological and clinical characteristics distributions were statistically different among the studied age groups. Known risk factors such as number of pregnancy and early age at menarche were statistically associated to CIN 2-3/cancer in the youngest group. In Brazil, 20.8% of pregnancies in 1994 occurred in adolescents, reaching 26% in 2000 [
On the other hand, finding age at menopause and current smoking habit independently associated to CIN 2-3/cancer in the group from 31 to 49 years old, could suggest that older women who are sexually active might be at higher risk of cancer development. Cruikshank et al. [
Surprisingly, none of the sexual behavior and environmental habits (smoking and oral contraceptive use) evaluated were significantly associated to CIN2-3/cancer among the oldest women group (50 - 68 years old). Since those women were aged 15 to 30 years old on 70’s sexual revolution, such findings could be probably due to both, either small number of older women in the sample study or a more conservative sexual behavior, such as late sexual onset, smaller number of sexual partner, stable marital status, late use of oral contraceptive and smoking habits. Since 1982, Murphy et al (1993) [
Besides diffusion of health promotion, including health education related to safe sexual behavior, smoking habits should also be considered in such programs. Current smoking habits were independently associated to the risk of developing CIN-2/3 and cancer among women from 31 to 49 years old, showing that special care must be taken about this issue. Because the health effects of smoking only become fully evident many years after the widespread uptake of smoking, the full global impact of smoking on women health will not be fully pictured for some decades. Many women, even in developed countries, are unaware of the extension of the risk of cervical cancer. In this sense, our study can provide evidence to support tobacco control programs focused on Brazilian women who are at higher risk of developing cervical cancer all over the country.
Present study limitations that must be addressed includes those inherent to cross- sectional studies, where exposures and outcomes are evaluated in a point of time. Thus, it is not possible to stablish causal association between exposures and outcome. Nevertheless, because of the latency period for cervical cancer development, the prevalence of known co-factors that may cumulatively affect the risk of this neoplasia (e.g. tobacco smoking, oral contraceptive use); and of those behavioral characteristics that may be a proxy of HPV infection opportunity in a lifetime (e.g. number of sexual partners, early menarche, late menopause, parity), may enable us to hypothesize about the changings occurred in the society concerning to risk of cervical cancer. Moreover, when such prevalence differ according to the generation based on a well described behavioral-impacting sociological event, such as the Sexual Revolution, such hypothesis become stronger. However, in order to test such hypothesis, analytical studies with greater sample size are required.
Present study suggests that risk factors for CIN-2/3/cervical cancer may have played different roles among generations of Brazilian women in Rio de Janeiro. In this sense, our data suggest that Brazilian women present distinct risk for cervical cancer according to the age group they belong, when taking the Brazilian sexual revolution on 70’s as a reference. Thus, among women from 18 to 30 years old, number of pregnancies and early age at menarche would be independently associated with CIN 2-3/cancer. However, among women from 31 to 49 years old, the independent risk factors for CIN 2-3/cancer would be age at menopause and smoking habits; while known behavioral risk factors would have smaller effect among women from 50 to 68 years old. Such findings suggest that cervical cancer control programs in Brazil should include smoking prevention among young women and smoking cessation among the oldest women. Pap smear exam adherence should be accomplished among all women sexually active, regardless their age, and public health advertisement must reach each age group of women, considering their cultural and generational differences.
This investigation was supported by the National Counsel of Technological and Scientific Development (CNPq), and the National Cancer Institute of Brazil (INCA).
da Silva, I.F., Koif- man, R.J., Parreira, V.A.G., Soares, S. and Koifman, S. (2017) Risk Factors for Cervical Cancer in a Sample Comprising Three Gene- rations of Brazilian Women. Journal of Can- cer Therapy, 8, 12-25. http://dx.doi.org/10.4236/jct.2017.81002