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Cigarette smoking and dysplasia and carcinoma in
situ of the uterine cervix.
Trevathan E; Layde P; Webster LA; Adams JB; Benigno BB; Ory
H
JAMA (United States) Jul 22-29 1983, 250 (4)
p499-502
We conducted a case-control study of cigarette smoking and
dysplasia and carcinoma in situ of the uterine cervix. Cases
were black women 17 to 55 years of age who were attending a
dysplasia clinic and had biopsy-confirmed cervical pathologic
conditions. Controls were women who were attending the family
planning clinic at the same hospital and who had at least two
normal Papanicolaou smears. Results were adjusted for age,
number of sexual partners, age at first intercourse,
socioeconomic status, and oral contraceptive use. Cigarette
smoking was significantly associated with carcinoma in situ ,
severe dysplasia, and mild-moderate dysplasia (relative risks,
3.6, 3.3, and 2.4, respectively). Cumulative exposure to
cigarette smoking (as measured by pack-years smoked) was
strongly related to the risk of these conditions; women with
12 or more pack-years of exposure had relative risks of 12.7,
10.2, and 4.3, respectively, for the three conditions. There
was some evidence that the risk was greatest in women who
began smoking in their early teenage years. A reduction in the
risk of cervical cancer appears to be another inducement for
young women not to smoke.
Smoking and carcinoma in situ of the uterine
cervix.
Lyon JL; Gardner JW; West DW; Stanish WM; Hebertson RM
Am J Public Health (United States) May 1983, 73 (5)
p558-62
We carried out a case-control study of 217 cases of in situ
carcinoma of the uterine cervix and 243 controls chosen from
the general population of Utah. We found a relative risk of
3.0 for cigarette smoking after controlling for sexual and
socioeconomic risk factors. The smoking association was
strongest in the youngest age group (ages 20-29), reaching
seventeenfold, and was weaker in the older age groups. These
data suggest that cigarette smoking may be an independent risk
factor for cancer of the uterine cervix, after considering
sexual behavior and other well-established risk factors.
Genetic damage in exfoliated cells of the uterine
cervix. Association and interaction between cigarette smoking
and progression to malignant transformation?
Cerqueira E.M.M.; Santoro C.L.; Donozo N.F.; Freitas B.A.;
Pereira C.A.D.B.; Bevilacqua R.G.; Machado-Santelli G.M.
Dr. E.M.M. Cerqueira, Av. Princesa Isabel, No. 114, Porto da
Barra, Salvador Bahia Brazil
Acta Cytologica (United States) 1998, 42/3
(639-649)
OBJECTIVE: To determine, through the micronucleus (MN)
test, the cytogenetic effects of cigarette smoking on
exfoliated cells from the uterine cervix in women with normal
smears and women with inflammatory atypia, squamous
intraepithelial lesion (SIL) (cervical intraepithelial
neoplasia [CIN] 1-3) and cervical cancer.
STUDY DESIGN: The study group consisted of 200 women
divided into three subgroups: group 1 (n = 116), women
periodically undergoing cervical cytology and residents of
Salvador-Bahia; group II (n = 57), women residing in Sao Paulo
and previously selected because of a possible cytopathologic
test positive for such conditions as human papillomavirus
infections or malignant or premalignant cervical lesions (CIN
1-3); group III (n=27), inmates of the Tatuape Penal
Institution, Sao Paulo. All the women underwent cytologic and
colposcopic examination, and biopsies were performed on 68 of
them.
RESULTS: Considering the sample as a whole and using the
chisup 2 test for rare events, the number of MNs in smokers
was significantly greater than in nonsmokers. It was also
greater in women with larger exposure to smoking . The
occurrence of MN was significantly lower in women with normal
smears (smokers or nonsmokers) than in those showing any kind
of pathologic alterations. In nonsmokers the occurrence of MN
was similar between those with inflammatory atypia (IA) or low
grade (L) SIL (CIN 1) and significantly higher in women with
more severe lesions or high grade (H) SIL (CIN 2 or 3).
Smokers with LSIL (CIN 1) showed a higher number of MNs than
nonsmokers with a comparable diagnosis and smokers with IA. No
differences were observed when compared with smokers with HSIL
(CIN 2 and 3). MN occurrence was not associated with other
risk factors for SIL or cancer development, such as age at
first coitus, number of sexual partners, multiparity and use
of hormonal contraceptives.
CONCLUSION: These results suggest that the mutagenic effect
of cigarette smoking occurs in cervical cells and that the
progression of SIL is associated with increased frequency of
chromosomaI damage. Moreover, the data suggest that cigarette
smoking introduces an additional risk to the progression of
low grade LSIL (CIN 1). MN testing would be helpful in
monitoring smokers with this kind of lesion.
Smoking and the antioxidant ascorbic acid: plasma,
leukocyte, and cervicovaginal cell concentrations in normal
healthy women.
Basu J; Mikhail MS; Payraudeau PH; Palan PR; Romney SL
Department of Obstetrics and Gynecology, Albert Einstein
College of Medicine, Bronx, NY 10461.
Am J Obstet Gynecol (United States) Dec 1990, 163 (6 Pt 1)
p1948-52
The influence of cigarette smoking on the plasma ,
leukocyte, and cervicovaginal cell ascorbic acid levels in 46
healthy smokers and healthy nonsmokers was investigated. Coded
peripheral venous blood and cervicovaginal lavage specimens
obtained after informed consent were analyzed simultaneously
for their ascorbic acid content. The findings suggest that
smoking affects the levels and distribution of ascorbic acid.
In smokers (n = 16), the number of exfoliated cervicovaginal
epithelial cells and leukocyte ascorbic acid levels was
significantly higher (p less than 0.01, p less than 0.05,
respectively) compared with nonsmokers (n = 30). In addition,
cervicovaginal cell ascorbic acid, plasma reduced and total
ascorbic acid levels were significantly lower (p less than
0.001, p less than 0.01, p less than 0.01, respectively). The
exfoliated epithelial cell ascorbic acid levels in nonsmokers
was fourfold greater than that of leukocytes. The implications
of these findings within the context of free radical-induced
cellular pertubations in smokers are discussed.
Annual variation of serum selenium in patients with
gynaecological cancer during 1978-1983 in Finland, a low
selenium area.
Sundstrom H
Int J Vitam Nutr Res (Switzerland) 1985, 55 (4)
p433-8,
To explore the relationship between selenium deficiency in
cancer and nutritional factors, we measured the serum
concentrations of selenium in 1978-1983 in patients with
gynaecological cancer (N = 277) and correlated these with the
estimated daily intake of selenium, which varies in Finland
depending on the proportion of selenium-rich imported grain.
The selenium concentration increased significantly from
1978-1979 to 1982 in the series of all cancer patients (p less
than 0.001) and separately in cases of cervical (p less than
0.001) and endometrial cancer (p less than 0.02), parallel to
the increased daily intake of selenium. The serum level of
selenium decreased in 1983, when the import of selenium-rich
grain was reduced. Low serum selenium in cancer patients thus
seems to be mainly dependent on dietary factors.
A case-control study of nutrient status and
invasive cervical cancer. I. Dietary indicators
Herrero R.; Potischman N.; Brinton L.A.; Reeves W.C.; Brenes
M.M.; Tenorio F.; De Britton R.C.; Gaitan E.
Environmental Epidemiol Branch, National Cancer Institute,
Executive Plaza North,Bethesda, MD 20892 United States
American Journal of Epidemiology (United States) 1991, 134/11
(1335-1346)
A study of 748 cases and 1,411 hospital and community
controls in four Latin American countries evaluated the
association between certain elements of diet and invasive
cervical cancer. Subjects were interviewed about their adult
consumption of 58 food items, including the major sources of
putative protective agents (vitamin A, carotenoids, vitamin C,
and folacin) as well as other behavioral and medical
characteristics related to cervical cancer. Participation
rates were above 95% for both cases and controls. After
adjustment for age, study site, sexual and reproductive
behavior, socioeconomic status, screening practices, and
detection of human papillomavirus 16/18 by filter in situ
hybridization, a slightly lower risk was observed for the
highest quartiles of consumption of fruit and fruit juices,
while no reductions in risk were associated with vegetables,
foods of animal origin, complex carbohydrates, legumes, or
folacin-rich foods. When nutrient indices were derived,
significant trends of decreasing risk were observed for
vitamin C (adjusted odds ratio (OR) = 0.69 for the highest vs.
the lowest quartile; p for trend = 0.003), beta-carotene (OR =
0.68; p = 0.02), and other carotenoids (OR = 0.61; p = 0.003).
Inclusion of vitamin C and beta-carotene in the same model
attenuated the association with beta-carotene, while the
association with vitamin C remained unchanged. The results are
consistent with those of other investigations and provide
support for a protective effect of vitamin C, carotenoids, and
other substances found in the same fruits and vegetables
against the development of invasive cervical cancer. However,
the fact that the associations were driven by relation in two
of the study sites and among women of higher socioeconomic
status leaves open the possibility of selection bias or
effects of unidentified aspects of dietary patterns.
The association of plasma micronutrients with the
risk of cervical dysplasia in Hawaii.
Goodman MT; Kiviat N; McDuffie K; Hankin JH; Hernandez B;
Wilkens LR; Franke A; Kuypers J; Kolonel LN; Nakamura J; Ing
G; Branch B; Bertram CC; Kamemoto L; Sharma S; Killeen J
Etiology Program, Cancer Research Center of Hawaii,
University of Hawaii, Honolulu 96813, USA.
Cancer Epidemiol Biomarkers Prev (United States) Jun 1998, 7
(6) p537-44
Limited data from hematological studies suggest that
certain nutrients, including carotenoids, tocopherols, and
vitamin C , may protect against malignant change in cervical
tissue. Recognizing that human papillomavirus (HPV) infection
induces most neoplastic transformation of cervical tissue, the
authors conducted a case-control study to examine the
association of plasma micronutrient concentrations with the
risk of cervical dysplasia after careful adjustment for HPV
infection, using a sensitive and reliable HPV detection
method. The sample included 147 multiethnic women, between 18
and 65 years of age, with biopsy-confirmed squamous
intraepithelial lesions (SILs) of the cervix and 191 clinic
controls identified between 1992 and 1996. Cases were
identified through cytology and pathology logs in three
clinics on Oahu, Hawaii. Controls were selected randomly from
admission logs of the participating clinics. In-person
interviews were conducted in the subjects' homes, and a
fasting blood sample was drawn to measure plasma levels of
lutein, lycopene, cryptoxanthin, total carotene, retinol,
tocopherol, ascorbic acid, and cholesterol. The presence and
type of HPV was determined in exfoliated cell samples using
PCR dot blot hybridization. Mean plasma lycopene, total
cryptoxanthin, and alpha-cryptoxanthin levels were lower among
cases than controls. We found an inverse dose-response of
alpha-cryptoxanthin, total tocopherol, and alpha-tocopherol to
the odds ratios for cervical SIL after adjustment for HPV and
other confounders. The odds ratio among women in the highest
compared with the lowest quartile was 0.3 (95% confidence
interval, 0.1-0.7) for alpha-cryptoxanthin and 0.3 (95%
confidence interval, 0.1-0.8) for alpha-tocopherol. Negative
trends in the odds ratios were suggested for other carotenoids
and vitamin C , but these were weak, and confidence intervals
were wide. Our results support existing evidence that high
plasma levels of antioxidants may reduce the risk of cervical
SILs independent of HPV infection. These findings are
significant because diet is potentially modifiable, and
nutrition education and dietary intervention might be targeted
at specific high-risk groups.
Can cervical dysplasia and cancer be prevented with
nutrients?
Giuliano AR; Gapstur S
Arizona Prevention Center, University of Arizona, Tucson
85724, USA.
Nutr Rev (United States) Jan 1998, 56 (1 Pt 1)
p9-16
Invasive cervical cancer accounts for 11.6% of all cancers
worldwide and is the second most common cancer among women. It
is the most common cancer among women living in less developed
countries. Although infection with oncogenic-type human
papillomaviruses (HPV) is associated with most cases of
cervical cancer, HPV infection alone is an insufficient cause
of cervical cancer. Research from the last two decades
suggests a role for nutrients in the prevention of cervical
cancer. However, results from phase III folic acid and
beta-carotene chemoprevention trials have been negative.
Potential reasons for the lack of treatment effect are
discussed within the context of cervical carcinogenesis. (51
Refs.)
Negative Diet and the risk of invasive cervical
cancer among white women in the United States.
Ziegler RG; Brinton LA; Hamman RF; Lehman HF; Levine RS;
Mallin K; Norman SA; Rosenthal JF; Trumble AC; Hoover RN
Environmental Epidemiology Branch, National Cancer Institute,
Bethesda, MD 20892.
Am J Epidemiol (United States) Sep 1990, 132 (3)
p432-45
A case-control study of incident invasive cervical cancer
was conducted in Birmingham, Alabama; Chicago, Illinois;
Denver, Colorado; Miami, Florida; and Philadelphia,
Pennsylvania, during 1982-1983. Controls were selected by
random-digit dialing and were matched to cases by age, race,
and telephone exchange. Of the white, non-Hispanic cases and
controls identified, 271 (73%) and 502 (74%), respectively,
were successfully interviewed. Diet was assessed by asking
about the usual adult frequency of consumption of 75 food
items and the use of vitamin supplements. Included were the
major sources of the four micronutrients believed to reduce
the risk of cervical cancer: carotenoids, vitamin A, vitamin
C, and folate. Women in the highest quartiles of intake of
each of these micronutrients had adjusted relative risks of
invasive squamous cell cervical cancer comparable to those of
women in the lowest quartiles, although their micronutrient
intake was estimated to be 3-4 times as high. Risk was not
affected by increased consumption of vegetables, dark green
vegetables, dark yellow-orange vegetables, fruits, or legumes,
or by high intake of the basic food groups. These generally
negative findings stand in contrast to findings in previous
epidemiologic studies, and the discrepancy is not readily
explained by bias, uncontrolled confounding, or inadequate
power. The question of the role of diet and nutrition in the
etiology of cervical cancer is not yet resolved.
Dietary factors in women with dysplasia colli uteri
associated with human papillomavirus infection.
Kwasniewska A; Charzewska J; Tukendorf A; Semczuk M
I Department of Obstetrics and Gynaecology, Lublin Medical
Academy, Poland.
Nutr Cancer (United States) 1998, 30 (1) p39-45
The studies were carried out in a group of 228 female
patients with normal cytological smear and 324 patients with
cervical intraepithelial neoplasia (CIN). The applied method
of human papillomavirus (HPV) identification, i.e., the HPV
digene hybrid capture system, made it possible to select a
control group consisting of 168 HPV-negative patients with
normal Papanicolaou smears, as well as a group of 228
HPV-positive female patients with CIN. By examining the diet
of the patients, it was shown that women with cervical
dysplasia associated with high oncogenic risk of HPV
infections consumed a smaller quantity of foods containing
vitamin C , beta - carotene , and folacin. Our studies
indicate a relationship between nutritional habits and the
development of CIN associated with HPV infection
Cervical intraepithelial neoplasia, cervical
cancer, and HPV
Holly E.A.
Epidemiol./Biostatistics Department, School of Medicine,
University of California,San Francisco, CA 94143 United
States
Annual Review of Public Health (United States) 1996, 17/-
(69-84)
Major progress has been made to control cervical cancer in
the United States and Europe using screening programs,
although it remains a major cause of morbidity and mortality
in the developing world. The association between cervical
cancer and a sexually transmissible etiologic agent was
hypothesized long before identification of human
papillomaviruses (HPV) as agents that infected the genital
tract. HPVs are among the most common sexually transmitted
agents and have been shown to induce several squamous
anogenital cancers, including squamous cell cancer of the
cervix. After an etiologic role for HPV was identified in
cervical cancer and CIN, efforts to understand the molecular
biology of HPV were greatly expanded, enhanced by the advent
of deoxyribonucleic acid (DNA) probes to identify HPV
infection. Recent research has focused on specific types of
HPV in relation to other recognized risk factors in the
pathogenesis of CIN and invasive cervical cancer.
Human papillomavirus and invasive cervical cancer
in Brazil.
Eluf-Neto J; Booth M; Munoz N; Bosch FX; Meijer CJ;
Walboomers JM
Departamento de Medicina Preventiva, Faculdade de Medicina,
Universidade de Sao Paulo, Brazil.
Br J Cancer (Scotland) Jan 1994, 69 (1) p114-9
A hospital-based case-control study was undertaken to
examine the role of human papillomavirus (HPV) in the
development of invasive cervical cancer in Brazil. The study
included 199 histologically confirmed incident cases and 225
age-frequency-matched controls selected from a wide range of
diagnostic categories. A polymerase chain reaction technique
was used to detect HPV DNA in cervical specimens collected
with spatula and brush. HPV DNA was detected in 84% of the
cases compared with 17% of controls. Grouping HPV types 16,
18, 31 and 33, 66% of the cases were positive compared with
only 6% of the controls. In addition to HPV, number of sexual
partners, early age at first intercourse, parity and duration
of oral contraceptive use were significantly associated with
an increased risk of cervical cancer. A history of previous
Papanicolaou smears was significantly associated with a
decreased risk. After adjustment, only presence of HPV DNA,
parity and history of previous smears remained as independent
risk factors. The adjusted odds ratios of cervical cancer
associated with HPV 16, 18, 31, and 33 was 69.7 (95%
confidence interval 28.7-169.6) and with unidentified types
was 12.0 (5.1-28.5). The very high risks found in this study
further implicate this virus in the aetiology of cervical
cancer.
Herpes simplex virus type 2: a possible interaction
with human papillomavirus types 16/18 in the development of
invasive cervical cancer.
Hildesheim A; Mann V; Brinton LA; Szklo M; Reeves WC; Rawls
WE
Environmental Epidemiology Branch, National Cancer Institute,
National Institutes of Health, Bethesda, MD 20892.
Int J Cancer (United States) Sep 30 1991, 49 (3)
p335-40
A case-control study of 766 histologically confirmed
incident cases of invasive cervical cancer and 1,532 hospital
and community controls was conducted in Latin America to
evaluate the etiologic role of herpes simplex virus type 2
(HSV-2) and to examine whether HSV-2 interacts with other risk
factors. In addition to a personal interview, all subjects
were asked to donate blood samples and cervical swabs for
assessment of exposure to HSV-2 and human papillomaviruses
(HPVs) respectively. Ninety-eight percent of cases and 91% of
controls agreed to the interview and blood collection. Women
testing positive for HSV-2 antibodies were found to have a 60%
increased risk of cervical cancer compared with seronegative
women (95% CI = 1.3, 1.9). Control for education, sexual and
reproductive behavior, prior Pap-smear screening, smoking,
oral contraceptive use , HPV-6/11 DNA, or HPV-16/18 DNA
detection did not materially affect this estimate. No effect
modification of HSV-2 by age, HPV-6/11 DNA, pregnancies, oral
contraceptive use or cigarette smoking was observed. However,
a significant interaction was detected between HSV-2 and
HPV-16/18. Compared with women testing negative to both virus
types, those positive for HSV-2 alone had a RR of 1.2 (95% CI
= 0.9, 1.6), those positive for HPV-16/18 DNA alone had a RR
of 4.3 (95% CI = 3.0, 6.0), and those positive for both
viruses had a RR of 8.8 (95% CI = 5.9, 13.0). These findings
corroborate recent laboratory evidence of a possible
biological interaction between HSV-2 and HPV-16/18 in the
development of cervical cancer. Further confirmatory studies
are needed, given concerns with potential misclassification of
exposure by the laboratory assays utilized.
Epidemiologic evidence showing that human
papillomavirus infection causes most cervical intraepithelial
neoplasia
Schiffman MH; Bauer HM; Hoover RN; Glass AG; Cadell DM; Rush
BB; Scott DR ; Sherman ME; Kurman RJ; Wacholder S; et al
Epidemiology and Biostatistics Program, National Cancer
Institute, National Institutes of Health, Bethesda, MD
20892.
J Natl Cancer Inst (United States) Jun 16 1993, 85 (12)
p958-64
BACKGROUND: Experimental studies have provided strong
evidence that human papillomavirus (HPV) is the long-sought
venereal cause of cervical neoplasia, but the epidemiologic
evidence has been inconsistent.
PURPOSE: Given improvements in HPV testing that have
revealed a strong link between sexual activity history and
cervical HPV infection, we conducted a large case-control
study of HPV and cervical intraepithelial neoplasia (CIN) to
evaluate whether sexual behavior and the other established
risk factors for CIN influence risk primarily via HPV
infection.
METHODS: We studied 500 women with CIN and 500 control
subjects receiving cytologic screening at Kaiser Permanente, a
large prepaid health plan, in Portland, Ore. The established
epidemiologic risk factors for CIN were assessed by telephone
interview. We performed HPV testing of cervicovaginal lavage
specimens by gene amplification using polymerase chain
reaction with a consensus primer to target the L1 gene region
of HPV. Unconditional logistic regression analysis was used to
estimate relative risk of CIN and to adjust the epidemiologic
associations for HPV test results to demonstrate whether the
associations were mediated by HPV.
RESULTS: The case subjects demonstrated the typical
epidemiologic profile of CIN: They had more sex partners, more
cigarette smoking, earlier ages at first sexual intercourse,
and lower socioeconomic status. Statistical adjustment for HPV
infection substantially reduced the size of each of these
case-control differences. Seventy-six percent of cases could
be attributed to HPV infection; the results of cytologic
review suggested that the true percentage was even higher.
Once HPV infection was taken into account, an association of
parity with risk of CIN was observed in both HPV-negative and
HPV-positive women.
CONCLUSION: The data show that the great majority of all
grades of CIN can be attributed to HPV infection, particularly
with the cancer-associated types of HPV.
IMPLICATIONS: In light of this conclusion, the
investigation of the natural history of HPV has preventive as
well as etiologic importance.
Viral characteristics of human papillomavirus
infection and antioxidant levels as risk factors for cervical
dysplasia.
Ho GY; Palan PR; Basu J; Romney SL; Kadish AS; Mikhail M;
Wassertheil-Smoller S; Runowicz C; Burk RD
Department of Epidemiology and Social Medicine, Albert
Einstein College of Medicine, Bronx, NY 10461, USA
ho@aecom.yu.edu
Int J Cancer (United States) Nov 23 1998, 78 (5)
p594-9
Genital human papillomavirus (HPV) infection is the major
causal factor of cervical intraepithelial neoplasia (CIN). The
potential role of nutrition as an additional, independent risk
factor for CIN has not been appropriately addressed in the
context of HPV. This case-control study evaluated the
etiologic role of HPV in terms of viral type and load and
examined the association between CIN and plasma levels of
micronutrients adjusting for HPV. Cases (n = 378) with
histo-pathologically confirmed CIN and controls (n = 366) with
no history of abnormal Pap smears were recruited from
colposcopy and gynecology clinics, respectively. Risk of CIN
was significantly increased among women who were infected with
multiple HPV types (odds ratio [OR] = 21.06), a high viral
load (OR = 13.08) and HPV 16 (OR = 62.49). After adjusting for
HPV positivity and demographic factors, there was an inverse
correlation between plasma alpha-tocopherol and risk of CIN
(OR = 0.15). Plasma ascorbic acid was protective at a high
level of > or = 0.803 mg/dl (OR = 0.46). CIN was not
associated with plasma retinol and beta - carotene levels. The
effect of genital HPV infection on CIN development is highly
influenced by oncogenic viral type and high viral load.
Vitamins C and E may play an independent protective role in
development of CIN that needs to be confirmed in prospective
studies.
A case-control study of nutrient status and
invasive cervical cancer. II. Serologic indicators
Potischman N.; Herrero R.; Brinton L.A.; Reeves W.C.;
Stacewicz-Sapuntzakis M.; Jones C.J.; Brenes M.M.; Tenorio F.;
De Britton R.C.; Gaitan E.
Environ. Epidemiology Branch, National Cancer
Institute,Bethesda, MD United States
American Journal of Epidemiology (United States) 1991, 134/11
(1347-1355)
A study of 387 cases and 670 controls from four Latin
American countries evaluated the hypothesis that lower serum
levels of eight micronutrients were associated with a higher
risk of invasive cervical cancer. The serologic analyses were
restricted to a sample of subjects with stage I and II disease
to minimize effects of the disease on the serologic markers.
Ninety-four percent of eligible subjects donated blood
samples, which were analyzed for carotenoids, retinol, and
tocopherols by high-pressure liquid chromatography. Cases did
not differ significantly from controls in mean serum levels of
retinol, cryptoxanthin, lycopene, alpha-carotene, lutein, or
alpha-tocopherol. The mean level of beta-carotene was lower
and the mean level of gamma-tocopherol was higher among cases
as compared with controls. After adjustment for age, study
site, sexual and reproductive behavior, socioeconomic status,
screening practices, detection of human papillomavirus types
16/18, cholesterol, and triglycerides, a trend of decreasing
risk was associated with higher levels of beta-carotene (p for
trend = 0.05), with the adjusted odds ratio decreasing to 0.72
for the highest versus the lowest quartile. beta-Carotene
results were similar by stage of disease, which argues against
an effect of disease progression on nutrient values.
Unexpectedly, increasing risks were observed as the level of
gamma-tocopherol increased (odds ratio = 2.09; p for trend =
0.03); however, levels were higher among stage II cases as
compared with stage I cases, suggesting a metabolic alteration
resulting from the disease process. The concordance in the
strength and direction of the blood and dietary results,
presented in the accompanying report (Herrero R, Potischman N,
Brinton LA, et al., American Journal of Epidemiology
1991;134:1335-46), supports a role for beta-carotene or foods
rich in beta-carotene in the etiology of cervical cancer. This
study also indicates that simultaneous analysis using
serologic and dietary nutrient indicators allows better
discrimination of the association.
The role of sexual factors in the aetiology of
cervical dysplasia
de Vet HC; Knipschild PG; Sturmans F
Department of Epidemiology, University of Limburg,
Maastricht, The Netherlands.
Int J Epidemiol (England) Oct 1993, 22 (5)
p798-803
The effect of sexual behavior on the risk for cervical
dysplasia was evaluated in a case-control study. Cases (n =
257) had a histologically confirmed diagnosis of cervical
dysplasia . Controls (n = 705) were sampled from the general
population. A postal questionnaire was used to obtain
information about, among other things, age at first sexual
intercourse, number of sexual partners, current frequency of
intercourse and contraceptive use. Information was also
collected about other risk factors for cervical dysplasia , in
order to adjust for possible confounding. We observed higher
risks for cervical dysplasia (mild, moderate and severe) with
increasing number of sexual partners. This effect appeared to
be dependent on smoking behaviour. For women who reported more
than six sexual partners, the adjusted odds ratio (aOR) was
9.1 (95% CI: 3.5-23.7) for non-smokers, and 26.4 (95% CI:
11.8-58.8) for women who smoked > or = 20 cigarettes per
day. The effects of age at first sexual intercourse and
current frequency of intercourse disappeared after adjustment
for other risk factors. Use of oral contraceptives for > 10
years increased the risk (aOR = 2.3; 95% CI: 1.2-4.6). Thus,
the number of sexual partners, especially in combination with
smoking behaviour, appeared to be the most important risk
factor for cervical dysplasia .
Risk factors for cervical dysplasia: implications
for prevention.
de Vet HC; Sturmans F
Department of Epidemiology, University of Limburg,
Maastricht, The Netherlands.
Public Health (England) Jul 1994, 108 (4) p241-9
This study assessed the aetiologic and public health
importance of various risk factors for cervical dysplasia. A
case-control design was used in which all cases had a
histologically confirmed mild, moderate or severe cervical
dysplasia. Controls were sampled from the general population.
A total of 257 cases and 705 controls returned a postal
questionnaire about marital status, sexual behaviour and
contraceptive use, smoking behaviour and dietary intake of
some nutrients . An increased risk was observed for women who
were smokers and women who reported more than one sexual
partner. For women who reported more than six sexual partners,
the adjusted odds ratio was 11.5 (95% CI: 6.6-20.2); for women
who smoked more than 20 cigarettes per day, an adjusted odds
ratio of 2.5 (95% CI: 1.6-3.9) was found. Use of oral
contraceptives for more than 10 years increased the risk: the
adjusted odds ratio was 2.3 (95% CI: 1.2-4.5). The population
attributable risk percentage (PAR%) of these three risk
factors together was 72%, while number of sexual partners,
number of cigarettes smoked and oral contraceptive use alone
amounted to a PAR% of 57%, 29% and 8% respectively.
Considering the preventive potential against the background of
causality of the relationships and the social acceptability of
the proposed changes, it is concluded that cervical cancer and
its precursors might for the greater part be prevented by
behavioural changes, such as reducing smoking and using
contraceptive barrier methods.
Risk factors in the development of cervical
intraepithelial neoplasia in women with vulval warts.
Walkinshaw SA; Dodgson J; McCance DJ; Duncan ID
Department of Obstetrics and Gynaecology, Ninewells Hospital,
Dundee.
Genitourin Med (England) Oct 1988, 64 (5)
p316-20
Of 59 women referred with vulval warts whose cervices were
assessed colposcopically for the presence of cervical
intraepithelial neoplasia (CIN) before local treatment of the
wart lesions, 17 had histologically proved CIN, 12 had
histologically proved cervical wart virus infection, and 30
had abnormality on colposcopy or cytology. Seven of the 17
with CIN had no abnormality on cervical cytology. No
differences in sexual behaviour, smoking habit, or oral
contraceptive use were seen between women with CIN and those
with no cervical abnormality. Viral DNA typing of the vulval
lesions was carried out, but there were no differences in the
distribution of viral types between the three different
histological groups. Of the 30 women with no abnormality at
the initial visit, 23 were followed up colposcopically and
cytologically for one to two years. Three of them developed
CIN after adequate treatment of the vulval lesions despite the
absence of cervical abnormalities on colposcopy at the time of
treatment. Studying the known factors linked with CIN failed
to show why some women with vulval warts develop CIN, even
after treatment of the warts, and others do not. The large
number of false negative results on cervical cytology in our
patients suggests that women presenting with vulval warts
should be screened colposcopically in the first instance.
Close follow up of women whose warts are treated and who are
thought to have no cervical abnormality at that assessment is
essential.
Quantification of HPV-16 E6-E7 transcription in
cervical intraepithelial neoplasia by reverse transcriptase
polymerase chain reaction.
Hsu EM; McNicol PJ; Guijon FB; Paraskevas M
Department of Medical Microbiology, University of Manitoba,
Winnipeg, Canada.
Int J Cancer (United States) Sep 30 1993, 55 (3)
p397-401
Human papillomavirus type 16 (HPV-16) is associated with
neoplastic lesions of the uterine cervix. Viral transforming
functions have been localized to the E6-E7 open reading frame
(ORF) and this ORF is conserved consistently in cervical
intraepithelial neoplasia (CIN). Two mRNAs, generated by
alternative splicing, are expressed from the E6-E7 ORF. These
are known as E6*I and E6*II, and potentially encode the viral
E7 and E6 proteins, respectively. It is believed that the
HPV-16 transforming ability is mediated by the E6 and E7
proteins. A quantitative RT-PCR assay, developed by us to
characterize the relative expression of E6-E7 spliced
transcripts, was applied to exfoliated cervical cells obtained
from patients in varying stages of clinically defined CIN and
who were infected with HPV-16. The relationship between viral
expression, disease stage, oral contraceptive use and age was
studied. No association was observed between age or oral
contraceptive use and HPV-16 E6-E7 expression. However, when
both E6*I and E6*II were detected, a direct correlation was
observed between relative proportions of E6*I/E6*II mRNAs
greater than 95%/5% and increased disease severity. This study
underscores the importance of the relationship between
quantities of viral transforming gene transcript and the
course of cervical disease. It also suggests that
quantification of HPV-16 E6-E7 transcription may be useful as
a prognostic tool to identify women who are at increased risk
of developing cervical cancer.
[A cohort study on cancer of uterine cervix in
Jingan county, Jiangxi province]
Yang XZ
Jiangxi Provincial Gyn. & Obs. Hospital, Nanchang.
Chung Hua Chung Liu Tsa Chih (China) Nov 1992, 13 (6)
p409-12
A cohort study on 24,628 married women beyond 30 years of
age in Jingan county, Jiangxi province was carried out from
1974 to 1985. It was equivalent to 207,490 person-year. The
results showed that the earlier the first sexual intercourse
the higher the risk of cervical cancer. There was a
significant linear trend. The relative risk (RR) of cervical
cancer in women increased from 1.63 to 6.85 with increase in
the number of sex partners from one to two or more. The risk
also increased from 1.44 to 5.38 and 2.69 as their husband had
one, two or three and more extramarital sex partners.
Irregular menstruation and insanitary mentrual pads were also
risk factors. Risk factors of menarche age, age of first
delivery, number of children, smoking and drinking were
balanced in the present analysis by the logistic regression
model.
A nuclear DNA study of uterine cervical dysplasia
with reference to its prognostic significance.
Yokosuka K; Sato K; Izutsu T; Kagabu T; Nishiya I; Wied
GL
Department of Obstetrics and Gynecology, Iwate Medical
University, Morioka.
Nippon Sanka Fujinka Gakkai Zasshi (Japan) Nov 1988 , 40 (11)
p1760-6
To further define the nuclear DNA content of uterine
cervical dysplasia and its relationship to prognosis and
epidemiological features, a retrospective study using
Papanicolaou stained cytological specimen and TICAS was
undertaken. 1. Dysplasia patients was common among young
females who had a background of low age first pregnancy,
multiple Gravidity-Parity, the complication of inflammation
and the use of hormonal contraceptives and progressed rapidly.
It is recommended that a test should be repeated within 2 to 3
months regardless of the severity of the dysplasia and
patients should be followed up for at least 2.5 to 3 years. 2.
The DNA histograms were classified into 3 types (A,B and C):
Type C, which had the stem line in an aneuploidy area, showed
more severe dysplastic cases. This may be due to the
proliferation rate and significant alternation in the
chromosomes and mitoses. Nuclear DNA analysis using TICAS and
Papanicolaou stained cytological material could discriminate
between the progressive group and the persistent or regressive
group. In addition, the mean nuclear area might be the best
indicator of prognosis in uterine cervical dysplasia.
Risk factors for cervical intraepithelial
neoplasia.
Parazzini F; La Vecchia C; Negri E; Fedele L; Franceschi S;
Gallotta L
Istituto di Ricerche Farmacologiche Mario Negri, Milan,
Italy.
Cancer (United States) May 1 1992, 69 (9)
p2276-82
To evaluate risk factors for cervical intraepithelial
neoplasia (CIN), data were collected in a case-control study
based on 366 patients (58 with CIN class 1, 70 with CIN class
2, and 238 with CIN class 3) and 323 control subjects with
normal cervical smears interviewed on selected days at the
same screening clinics where cases had been identified. No
relationship emerged between indicators of socioeconomic
status (education and social class) and risk of mild/moderate
(considered together) and severe dysplasia. A total of 55
(43%) patients with CIN class 1 or 2, 107 (45%) patients with
CIN class 3, and 94 (29%) controls were current smokers. The
corresponding relative risk (RR) estimates for current versus
never smokers were 1.9 (95% confidence interval [CI] 1.2 to
3.0) for patients with CIN class 1 or 2 and 2.5 (95% CI 1.7 to
3.6) for patients with CIN class 3, and the risk increased
with the number of cigarettes smoked per day. No relationship
was observed between oral contraceptive use , parity,
spontaneous or induced abortions and the risk of CIN, but
patients tended to report earlier age at first birth than
control subjects. Compared with women reporting their first
birth before the age of 20 years, the risk estimates were 0.5
and 0.4, respectively, for patients with CIN 1 or 2 and
patients with CIN 3 in women reporting first birth at 20 to 24
years of age. The risk estimates were 0.5 and 0.6 for those
reporting their first birth at age 25 or later, but the trends
in risk were not statistically significant. The number of
sexual partners was directly associated with the risk for both
histopathologic subgroups. Compared with women reporting no
intercourse or their first intercourse after 22 years of age,
women with first intercourse before the age 18 had a RR
estimate of CIN class 1 or 2 of 2.3 and of CIN class 3 of 2.4,
with the trends in risk being statistically significant. This
study confirms considerable similarities in the epidemiology
of mild/moderate and severe cervical dysplasia. In addition,
it suggests consistency between the epidemiology of
intraepithelial and invasive cervical neoplasia for risk
factors that are likely to act on one of the first stages of
the process of carcinogenesis (i.e., indications of sexual
habits) but differences for hormone-mediated factors (i.e.,
reproductive variables or oral contraceptives).
Risk factors for cervical neoplasia in
Denmark.
Kjaer SK
Danish Cancer Society, Institute of Caner Epidemiology,
Copenhagen, Denmark.
APMIS Suppl (Denmark) 1998, 80 p1-41
With the overall goal of elucidating the risk factor
pattern for cervical neoplasia, two case-control studies and a
prospective cohort study were conducted. The first
case-control study focused on female lifestyle risk factors.
It was designed to include all women (aged 20-49 years) in
Greater Copenhagen, diagnosed with invasive cervical cancer or
carcinoma in situ (CIS) from January 1985 to December 1986.
They were identified from the Danish Cancer Registry. An
age-stratified control group was randomly selected from the
study area by means of The Danish Central Population Register.
Information on risk factors was collected using a
self-administered questionnaire. The study, which included 586
women with CIS, 59 women with cervical cancer, and 614 control
subjects, confirmed that CIS and invasive cervical cancer
share similar risk factors. Both disease entities were
strongly associated with sexual and venereal factors. This
applied especially to lifetime number of sexual partners and
age at first episode with genital warts (proxy measure for
human papillomavirus (HPV)), supporting that HPV infection in
the adolescent cervix is associated with a higher risk of
cervical neoplasia compared with such an infection later in
life. Our results also suggested that parity, oral
contraceptive use , and smoking may be important risk factors.
In the second case-control study, we identified all women with
one lifetime sexual partner based on the questionnaire
information obtained in the first case-control study. To
investigate the role of the "male factor", the women were
invited to participate in the study together with their
husband. In all, 41 case couples and 90 control couples were
enrolled. Data collection included a personal interview, blood
samples, and penile swabs from the males. The most significant
risk determinants of cervical neoplasia were a history of
genital warts in the male and non-use of condoms, emphasizing
the venereal nature and pointing to HPV as an important agent.
Genital warts are usually associated with the low-risk HPVs
(types 6 and 11) rather than with the high-risk HPV types.
However, an explanation for the observed relationship between
risk of cervical neoplasia and genital warts in the woman
herself and in her male partner could be, that they are more
likely also to harbour the high-risk HPV types. Only 2 case
husbands and no control husbands had HPV DNA detected in the
penile swabs (ViraPapR, ViraTypeTM). As the number of cells in
the swab always exceeded 3 x 10(4), the result may reflect
shortcomings in the test kit used. From our population-based
prospective cohort study of 11,088 women, we selected the
prevalent cases (199 women with LSIL/HSIL(low-grade/high-grade
squamous intraepithelial neoplasia), 131 women with ASCUS
(atypical squamous cells of undetermined significance)), and
1000 random controls (women and normal cervical cytology). At
enrollment, the women were personally interviewed and had a
gynecological examination including cervical swabs for HPV
testing and a Pap smear. HPV DNA detection was done using
polymerase-chain-reaction methods. Cervical HPV infection
(especially with the high-risk types) was the out-standing
risk factor for all grades of neoplasia, the association being
strongest for HSIL. Women with high-risk HPV infection had a
nearly 33-fold increased risk of HSIL compared to HPV-negative
women. Possible risk factors for cervical neoplasia in
HPV-positive women included smoking, non-use of barrier
contraceptives and parity. If analysis was restricted to
histologically confirmed high-grade lesions, the proportion of
cases that could be attributed to HPV infections was 80%. The
importance and urgent need for studies which include HPV as an
adjunct to cervical cytology is emphasized. Greater effort
should be made to determine the usefulness of this modality
(HPV diagnostics) in cervical cancer screening or in the
management of cervical neoplasia, especially ASCUS and
LSIL.
Correlation of cervical cancer mortality with
reproductive and dietary factors, and serum markers in
China
Guo W.-D.; Hsing A.W.; Li J.-Y.; Chen J.-S.; Chow W.-H.; Blot
W.J.
National Cancer Institute, 6130 Executive Blvd EPN
415,Bethesda, MD 20892-7368 United States
International Journal of Epidemiology (United Kingdom) 1994,
23/6 (1127-1132)
Background. Cervical cancer is the second leading cause of
cancer death among Chinese women. Within China, a considerable
geographical variation in mortality rates has been observed,
but the reasons are not well understood. Methods. Cervical
cancer rates were examined in relation to indices of
reproductive factors, dietary habits, and selected serum
biomedical markers in 65 rural Chinese counties. Results.
Cervical cancer mortality rates correlated positively and
significantly with antibodies to herpes simplex virus type 2
(HSV-2) (r = 0.40, P < 0.01), serum levels of ferritin (r =
0.33, P < 0.01), body mass index (BMI) (r = 0.42, P <
0.01) and cigarette smoking (r = 0.51, P < 0.05) and
negatively and significantly with age at first birth (r =
-0.51, P < 0.01), consumption of green vegetables (r =
-0.40, P < 0.01) and animal foods (r = -0.40, P < 0.01),
and serum levels of selenium (r = -0.26, P < 0.05). When
these variables were considered in the multiple regression
analysis, early age at first birth and higher BMI were
positively associated with cervical cancer mortality, while
consumption of green vegetables and animal foods were
negatively correlated. In the serum model, infection with
HSV-2 and low levels of sex hormone binding globulin (SHBG)
were positively related to cervical cancer mortality. No
relation was found for consumption of fruits. Conclusions.
Although limitations of these ecologic data preclude causal
inferences, findings in this study, including associations
with HSV-2 infection, early age at first birth, consumption of
green vegetables and animal foods, may provide clues to
cervical cancer aetiology.
Spontaneous evolution of intraepithelial lesions
according to the grade and type of the implicated human
papillomavirus (HPV)
Syrjanen K.J.
Dept. of Pathology/Forensic Medicine, University of Kuopio,
POB 1627,FIN-70211 Kuopio Finland
European Journal of Obstetrics Gynecology and Reproductive
Biology (Ireland) 1996, 65/1 (45-53)
Because of the fact that any meaningful classification
should bear a close relationship to the biological behavior of
the lesions, the usefulness of all new classifications of
cervical precancer lesions can only be established by well
controlled prospective follow-up studies. However, several
methodological and conceptual problems are encountered in the
natural history studies conducted during the past several
decades. While reviewing the available prospective follow-up
studies on cervical intraepithelial neoplasia (CIN), Ostor
(1993) found 3529 cases of CIN 1, of which 57% showed
regression, persistence was found in 32%, progression to CIN
III in 11%, and progression to invasive cancer in 1% of cases.
The corresponding figures for CIN II were 43%, 35%, 22%, and
5%, respectively. The recognition of the association between
human papillomavirus (HPV) and CIN has further complicated the
assessment of the natural history of cervical precancer
lesions. Results from the early prospective follow-up studies
are remarkably consistent, however. Progression from HPV-NCIN
(i.e., koilocytosis without CIN) to CIN I or greater was
reported for 18 (8%) of 232 women followed by Syrjanen et al.
for an average of 25 months, for 26 (8%) of 314 women followed
by de Brux et al. (1981) for 15 to 18 months, and for 113
(13%) of 846 women followed for up to six years by Mitchell et
al. During a 42-month follow-up period, 10% progression rate
was found in 1269 women with HPV-CIN I, and in 17% of 762
women with HPV-CIN II by de Brux et al. (1983). The
spontaneous regression rates were 53% and 39% in these
cohorts, respectively. This is fully consonant with our
experience from an almost 14-year follow-up of 530 women in
Kuopio, where the spontaneous regression rate seems to
increase in parallel with the extent of the follow-up time,
currently being 66.7% for HPV-NCIN and 55.7% for HPV-CIN I.
The figures for progression are 6.3% and 14.2%, respectively.
It is obvious that the probability of a cervical precancer
lesion to progress into an invasive disease increases with the
severity of the atypia. Another distinct prognostic factor is
HPV type, HPV 16 lesions possessing a significantly higher
risk for progression than infections by other HPV types. The
follow-up data also indicate, however, that even the high
grade lesions may spontaneously regress, which should have
important implications in therapy. The continuous problem
still remains; these natural history observations only apply
to a large series of women but are of little help in
predicting the disease outcome in individual women.
Plasma ascorbic acid and beta- carotene levels in
women evaluated for HPV infection, smoking, and cervix
dysplasia.
Basu J; Palan PR; Vermund SH; Goldberg GL; Burk RD; Romney
SL
Department of Obstetrics and Gynecology, Albert Einstein
College of Medicine, Bronx, NY 10461.
Cancer Detect Prev (United States) 1991, 15 (3)
p165-70
The association of the plasma levels of the essential
micronutrients, ascorbic acid and beta-carotene, with smoking
and human papillomaviruses (HPV) infection has been studied in
75 women referred to a colposcopy clinic for an abnormal Pap
smear. Each patient had a repeat Pap smear and a
colposcopically directed biopsy of a visually perceived cervix
abnormality. Cervicovaginal lavage specimen and peripheral
venous blood sample were obtained for HPV DNA hybridization
studies and nutrient analyses, respectively. Samples were
obtained and analyzed without knowledge of each woman's
clinical status. A group of 45 subjects had
histopathologically diagnosed dysplasias of varying grades of
severity. Among women with dysplasias, 53.3% were smokers. Of
subjects with and of subjects without dysplasias, 66 and 34%,
respectively, were positive for HPV infection. The mean plasma
reduced ascorbic acid, retinol, and beta-carotene levels
between the dysplastic groups were comparable. A strong
association with smoking history and plasma reduced ascorbic
acid level was note independent of cervical dysplasias or HPV
status. The findings underscore the importance of smoking,
ascorbic acid, and beta-carotene as nutritional variables, and
HPV infection in the pathogenesis of cervical dysplasias.
Nutrients in diet and plasma and risk of in situ
cervical cancer
Brock K.E.; Berry G.; Mock P.A.; MacLennan R.; Truswell A.S.;
Brinton L.A.
Department of Public Health, Human Nutrition Unit, University
of Sydney, Sydney, NSW Australia
Journal of the National Cancer Institute (United States)
1988, 80/8 (580-585)
Both plasma and dietary measures of vitamin A status were
investigated along with previously established risk factors
(number of sexual partners, age at first intercourse, smoking,
and oral contraceptive use) in a study of 117 in situ cervical
cancer patients and 196 matched community controls in Sydney,
Australia. Neither total calories nor retinol from foods was
related to cancer risk, nor was plasma retinol. When plasma
and dietary indexes were considered together, vitamin C, fruit
juices, and plasma beta-carotene showed protective effects.
Plasma beta-carotene reduced risk from top to bottom quartile
by 80%, vitamin C by 60%, and fruit juices by 50%. Thus the
evidence suggests that cancer risk is associated with some
aspect of diet that is reflected in the effect of plasma
beta-carotene. There is no clear effect of any one nutrient
but fruit juices appear protective. Thus vitamin C and
beta-carotene are likely candidates.
The role of vitamins in the etiology of cervical
neoplasia: An epidemiological review
Schneider A.; Shah K.
Department of Obstetrics and Gynecology, University of Ulm,
D-7900 Ulm Germany
Archives of Gynecology and Obstetrics (Germany ) 1989, 246/1
(1-13)
Diet may act as a cofactor in the development of cancer of
the cervix. A consistent correlation exists between low tissue
concentrations, low serum level, and low intake of vitamin A,
beta-carotene, vitamin C, or folic acid and an increased
prevalence of cervical neoplasia. A moderate effect is seen in
clinical trials with vitamin treatment of cervical
intraepithelial neoplasias. The studies reviewed here were not
consistent especially in the choice of controls and methods
for the assessment of dietary and confounding factors. Proper
morphologic identification of cervical intraepithelial
neoplasia was not always achieved. Longitudinal and
prospective cohort studies using more reliable methods for
diet monitoring may be valuable for future research in this
field.
Beta- carotene levels in exfoliated cervicovaginal
epithelial cells in cervical intraepithelial neoplasia and
cervical cancer.
Palan PR; Mikhail MS; Basu J; Romney SL
Department of Obstetrics and Gynecology, Albert Einstein
College of Medicine, Bronx, NY 10461.
Am J Obstet Gynecol (United States) Dec 1992, 167 (6)
p1899-903
OBJECTIVE: The purpose of this study was to measure
beta-carotene levels in exfoliated epithelial cervicovaginal
cells collected by a lavage technique in normal women and
patients with histopathologically diagnosed cervical
intraepithelial neoplasia and cervical cancer.
STUDY DESIGN: In a cross-sectional sampling of women (n =
105), cervicovaginal cells and plasma beta-carotene levels
were assayed with high-pressure liquid chromatography. In
addition, beta-carotene levels were measured in exfoliated
epithelial samples of cervicovaginal cells obtained from women
(n = 24) enrolled in an ongoing oral beta-carotene
supplementation clinical trial.
RESULTS: Cervicovaginal cells and plasma beta-carotene
levels were found to be significantly decreased in women with
cervical intraepithelial neoplasia and cervical cancer as
compared with controls (p < 0.0001, analysis of variance).
Retinol levels in cervicovaginal cells were undetectable. The
beta-carotene levels in cervicovaginal cells were markedly
increased in the majority of patients (79%) after oral
supplementation as compared with baseline levels in women
enrolled in the beta-carotene clinical trial.
CONCLUSION: The study demonstrates that changes of in situ
cellular beta-carotene concentrations are measurable in
samples of exfoliated epithelial cells obtained by a
noninvasive saline lavage harvesting technique. The current
findings further support our previous hypothesis that
beta-carotene deficiency may have an etiologic role in the
pathogenesis of cervical intraepithelial neoplasia and/or
cervical cancer.
Dietary vitamin C and uterine cervical
dysplasia
Wassertheil-Smoller S.; Romney S.L.; Wylie-Rosett J.; et
al.
Dept. Commun. Hlth, Albert Einstein Coll. Med., Bronx, NY
10461 United States
American Journal of Epidemiology (United States) 1981, 114/5
(714-724)
A case-control study of women with cervical abnormalities
identified through Pap smears, was conducted in the Bronx, New
York, to explore the relationship between nutritional intake
and cervical dysplasia. Nutrient intake was estimated from
computer analysis of three-day food records and 24-hour recall
for 169 study participants (87 cases, 82 controls), including
a subset of 49 pairs matched for age, race and parity. Mean
vitamin C intake per day from three-day food record for
controls was 107 mg, compared to 80 mg for cases (p <
0.01). Analysis of matched pairs showed similar results; 29%
of cases compared to 3% of controls in matched subset had
vitamin C intake less than 50% of the recommended daily
allowance, yielding a ten-fold increase in risk of cervical
dysplasia as estimated by odds ratio (p < 0.05). Younger
age, greater frequency of sexual intercourse and younger age
at first intercourse were associated with higher risk of
cervical dysplasia. Multiple logistic analyses indicated that
low vitamin C intake is an independent contributor to risk of
severe cervical dysplasia when age and sexual activity
variables are controlled. Approximately 35% of US women in
their reproductive years have daily vitamin C intake below 30
mg, and 68% have vitamin C intake below 88 mg. If other
studies confirm these findings, it may be important to explore
a possible protective role of supplementary vitamin C for
women at high risk of cervical cancer.
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