Plasma concentrations of coenzyme Q10 and tocopherols in cervical intraepithelial neoplasia and cervical cancer.

Cervical intraepithelial neoplasia (CIN) may, at times, unpredictably progress to invasive carcinoma of the cervix. Epidemiological nutritional studies suggest that higher dietary consumption and circulating levels of certain micronutrients may be protective against cervical cancer. However, a preventive role of dietary antioxidants in CIN is not well established. The purpose of this cross-sectional study was to investigate the comparative plasma concentrations of three potent antioxidants, coenzyme Q(10,) alpha-tocopherol and gamma-tocopherol, in women with normal Pap smears and patients with a biopsy-confirmed histopathological lesion diagnosed as CIN or cervical cancer. Plasma concentrations of coenzyme Q(10,) alpha-tocopherol and gamma-tocopherol were measured by high-pressure liquid chromatography in both normal women without any history of abnormal Pap smears (n=48), and patients with histopathologically confirmed diagnoses of: (a) CIN I, n=98; (b) CIN II, n=49; (c) CIN III, n=10; and (d) cervical cancer, n=25. The mean plasma levels of coenzyme Q(10), alpha-tocopherol and gamma-tocopherol were significantly lower (P<0.001,<0.001, and<0.001, respectively by Kruskal-Wallis test) in patients with various grades of CIN and cervical cancer compared with controls. After controlling for age and smoking, an inverse association between histological grades of epithelial lesions and both plasma coenzyme Q(10) and alpha-tocopherol concentrations was observed. The low plasma concentrations of coenzyme Q(10) may be due to deficient dietary intake or a decrease in endogenous coenzyme Q(10) biosynthesis that may reflect increased utilization as a result of free radical reactive oxygen species induced oxidative stress. Further molecular studies on the mechanistic role of antioxidants in women with precancer cervical lesions are needed.

Placental and serum levels of carotenoids in preeclampsia.

OBJECTIVE: We compared placental tissue, maternal serum, and umbilical cord venous blood levels of four dietary carotenoids (alpha-carotene, beta-carotene, lycopene, and canthaxanthin) in normal pregnant women and those with preeclampsia. METHODS: Levels of alpha-carotene, beta-carotene, lycopene, and canthaxanthin were measured in placental tissue, maternal serum, and umbilical cord venous blood from 22 normal pregnant women and 19 women with preeclampsia. The criteria for recruitment included gestational age of 30-42 weeks, singleton pregnancy, intact membranes, absence of labor contractions, and absence of any other medical complication concurrent with preeclampsia. Carotenoids were measured using high-pressure liquid chromatography. RESULTS: All four carotenoids were detectable in human placental tissue, maternal serum, and umbilical cord venous blood samples. The levels of beta-carotene, lycopene, and canthaxanthin in placentas from preeclamptic women were significantly lower (P =.032, .009, and .013, respectively, by Mann-Whitney test) than those from normal pregnant women. Maternal serum levels of beta-carotene and lycopene were significantly lower (P =.004 and .008, respectively, by Mann-Whitney test) in women with preeclampsia. However, umbilical cord venous blood levels of these carotenoids were not significantly different between the two groups. CONCLUSION: Lower placental tissue and maternal serum carotenoid levels in women with preeclampsia suggest that oxidative stress or a dietary antioxidant influence might have an effect on the pathophysiology of preeclampsia.

Viral characteristics of human papillomavirus infection and antioxidant levels as risk factors for cervical dysplasia.

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.

HPV 16 and cigarette smoking as risk factors for high-grade cervical intra-epithelial neoplasia.

Although genital human papillomavirus (HPV) infection is well established as the etiologic agent for cervical intraepithelial neoplasia (CIN), little is known about the cofactors involved in the development of high-grade lesions or the progression of low-grade to high-grade lesions. In our study of HPV-infected women with CIN (163 CIN I, 51 CIN II and 44 CIN III), women with CIN II or III were compared with those with CIN I for risk factors associated with high-grade lesions. After controlling for age, education, ethnicity and frequency of Pap smear screening, infection with HPV 16, but not high viral load or infection with multiple types, was associated with high-grade lesions (OR for CIN II = 11.96, OR for CIN III = 23.74). Risk of CIN III, but not CIN II, increased with number of cigarettes smoked per day (ORs = 1.49 and 3.35 for < or = 10 and > 10 cigarettes per day, respectively) and decreased with frequency of condom use during sex (ORs = 0.60 and 0.32 for women who used condoms occasionally/sometimes and most/all of the time, respectively). There were no associations between high-grade lesions and plasma levels of micronutrients (retinol, beta-carotene, alpha-tocopherol and reduced ascorbic acid). Our results indicate that infection with HPV 16 is associated with high-grade lesions. Additional cofactors, such as cigarette smoking, may be required as a carcinogen to advance HPV-infected cells toward neoplastic progression.

Plasma concentrations of micronutrients during a nine-month clinical trial of beta-carotene in women with precursor cervical cancer lesions.

The effects of oral supplementation of a 30-mg dose of beta-carotene on the plasma levels of carotenoids, tocopherols, and retinol were studied sequentially in 69 patients participating in a nine-month randomized placebo controlled trial conducted to examine efficacy of beta-carotene to induce regression of cervical intraepithelial neoplasia. At each visit (baseline and 1.5, 3, 6, 9, 10.5, and 15 mo), blood samples were collected and the levels of six micronutrients were determined by high-performance liquid chromatography. No limitations or changes were introduced in each participant's dietary habits. Cervico-vaginal lavage samples were also obtained at the same visit and assayed for the presence of human papillomavirus DNA by Southern blot hybridization and polymerase chain reaction. In the supplemented group, mean plasma beta-carotene levels were significantly higher (p = 0.0001) than baseline and remained markedly elevated for 15 months. In the longitudinal analysis of the placebo group, there were no variations among individual mean plasma levels of beta-carotene, alpha-carotene, lycopene, retinol, gamma-tocopherol, or alpha-tocopherol, suggesting absence of seasonal or dietary changes. In the placebo group, cigarette smoking and steroid contraceptive use were significantly associated with low levels of plasma beta-carotene (p = 0.05 and p = 0.012, respectively). However, in contrast, in the beta-carotene-supplemented group, steroid contraceptive use had no influence on the plasma beta-carotene levels. An additional noteworthy finding was that beta-carotene supplementation did not reverse the depletion effect in smokers. There was no association between the plasma levels of these six micronutrients in women with cervical intraepithelial neoplasia and persistent human papillomavirus infection status in the placebo or the supplemented groups. Functional sequential nutrient interactions with each other or with other essential micronutrients and possible long-term toxicity need to be addressed in clinical trials.

Effects of beta-carotene and other factors on outcome of cervical dysplasia and human papillomavirus infection.

Women with histopathologically confirmed cervical intraepithelial neoplasia (CIN) were followed at 3-month intervals in a randomized double-blinded trial to evaluate the efficacy of beta-carotene to cause regression of CIN. Questionnaire data, plasma levels of micronutrients, and a cervicovaginal lavage for human papillomavirus (HPV) detection were obtained at each visit, and an endpoint biopsy was performed at 9 months. Sixty-nine subjects had a biopsy endpoint evaluation; 9 of 39 (23%) subjects in the beta-carotene group versus 14 of 30 (47%) in the placebo group had regression of CIN (P = 0.039). Independent risk factors for persistent CIN at 9 months included type-specific persistent HPV infection (OR = 11.38, P = 0.006) and continual HPV infection with a high viral load (OR = 14.25, P = 0.007) at baseline and 9 months, an initial diagnosis of > or =CIN II (OR = 6.74, P = 0.016), and older age (OR for > or =25 years = 4.10, P = 0.072). After controlling for these factors, the beta-carotene and placebo groups did not differ in risk for having CIN at 9 months (OR = 1.53, P = 0.550). Resolution of baseline HPV infection was significantly correlated with non-high-risk HPV types (RR = 2.94, P = 0.015), age <25 years (RR = 2.62, P = 0.014), and douching after sexual intercourse (RR = 3.02, P = 0.012), but not with randomization group. Our data indicate that a large proportion of mild CIN lesions regress; age and HPV infection play an important role in the natural course of CIN; and repeated HPV testing may have a value in distinguishing women who need aggressive treatment for CIN versus those who do not. Supplementation of beta-carotene does not appear to have a detectable benefit in treatment of CIN.

Induction of transforming growth factor beta-1 in cervical intraepithelial neoplasia in vivo after treatment with beta-carotene.

Transforming growth factor (TGF) beta1 is a potent growth inhibitor of epithelial cells. Loss of responsiveness to TGF-beta1 and/or loss of TGF-beta1 itself may be important in the progression of cervical intraepithelial neoplasia to invasive cervical cancer. Retinoids have antiproliferative effects on epithelial cells and have been used as chemopreventive and chemotherapeutic agents for several human cancers. There is evidence that retinoids exert their effects by promoting the induction of TGF-beta. The aim of this study was to determine whether the expression of TGF-beta1 was altered in patients enrolled in a clinical trial designed to test the therapeutic efficacy of beta-carotene, a carotenoid metabolized to retinol, in cervical intraepithelial neoplasia. Using an immunohistochemical technique, tissues were stained with two types of antisera that react with the intracellular and extracellular forms of TGF-beta1. Matched cervical biopsies taken from 10 patients before and after treatment with beta-carotene were immunostained simultaneously to allow direct comparison of relative staining intensity. A significant increase in intracellular TGF-beta1 immunoreactivity was noted in cervical epithelial cells in patients with cervical intraepithelial neoplasia after treatment with beta-carotene (P = 0.003). These results demonstrate regulation of a TGF-beta isoform in vivo in humans in response to beta-carotene administered as a chemopreventive agent.

Plasma levels of beta-carotene, lycopene, canthaxanthin, retinol, and alpha- and tau-tocopherol in cervical intraepithelial neoplasia and cancer.

Epidemiological studies continue to identify an association of dietary antioxidant micronutrients in cancer prevention. A number of case-control and cohort studies have demonstrated a relationship between high intake of foods rich in carotenoids, tocopherols, and vitamin C with a reduced risk of certain human malignancies. The purpose of this study was to investigate the comparative plasma levels of a profile of known dietary antioxidants, namely, beta-carotene, lycopene, canthaxanthin, retinol, alpha-tocopherol, and tau-tocopherol. The target population was women with a histopathological diagnosis of cervical intraepithelial neoplasia (CIN) or cervical cancer and a control group. All women resided in the same catchment area (Bronx Borough, New York City) and were of similar inner-city socioeconomic backgrounds representing a fairly homogenous population group. A cross-sectional sample of 235 women was recruited with informed consent. Plasma nutrient levels were measured by reverse-phase high pressure liquid chromatography under study codes. The mean plasma levels of carotenoids (beta-carotene, lycopene, and canthaxanthin), as well as alpha-tocopherol, were significantly lower in women with CIN and cervical cancer. In contrast, the mean plasma level of tau-tocopherol was higher among patients with CIN, while the mean plasma level of retinol was comparable among the groups. There were significant linear trends for all three carotenoids and quadratic trends for alpha- and tau-tocopherol with the degree of cervical histopathology. Plasma beta-carotene concentrations in cigarette smokers were significantly lower regardless of cervical pathology, whereas plasma lycopene and canthaxanthin levels were significantly lower in smokers with CIN. The findings of a decrease in all plasma antioxidant nutrient levels except tau-tocopherol in women with CIN and cancer suggest a potential role for antioxidant deficiency in the pathogenesis of CIN and carcinoma of the cervix, which requires further investigation.

Effects of smoking on the levels of antioxidant beta carotene, alpha tocopherol and retinol in human ovarian follicular fluid.

The concentrations of beta-carotene, retinol and alpha-tocopherol were measured by high-pressure liquid chromatography in ovarian follicular fluid and plasma samples collected at the time of oocyte recovery from patients enrolled in our in vitro fertilization program. The mean beta-carotene levels in follicular fluid [0.182 +/- (SEM) 0.04 nmol/ml] and plasma (0.37 +/- 0.34 mmol/ml) of smokers (n = 5) were significantly (p < 0.025 and p < 0.001, respectively) lower compared with the mean levels in follicular fluid (0.58 +/- 0.10 nmol/ml) and plasma (1.11 +/- 0.09 mmol/ml) in nonsmokers (n = 11). The follicular fluid and plasma retinol and alpha-tocopherol levels were comparable among the nonsmokers and smokers. These findings direct attention to a possible role of the antioxidant beta-carotene, per se, as a biological marker in ovarian oocyte follicular maturation and function.

Lipid profile in women with preeclampsia: relationship between plasma triglyceride levels and severity of preeclampsia.

It has been hypothesized that, in preeclampsia, hypertriglyceridemia may lead to increased endothelial triglyceride accumulation that, in turn, may result in endothelial cell damage. The purpose of our study was to determine whether hypertriglyceridemia is associated with the severity of preeclampsia. We studied 29 preeclamptic patients and 46 normal pregnant women, aged 15 to 35 years, with singleton pregnancies, at 28 to 37 weeks' gestation. Total cholesterol, low-density lipoprotein cholesterol, and triglyceride levels were measured enzymatically. High-density lipoprotein cholesterol was determined using a dextran sulfate-magnesium precipitation method. Patients with mild preeclampsia had a significant increase in plasma triglyceride levels (P < .001), while patients with severe preeclampsia had triglyceride levels comparable to controls. Our findings suggest that there is no direct relationship between triglyceride levels and severity of preeclampsia.

Nutrient antioxidants in the pathogenesis and prevention of cervical dysplasias and cancer.

The role of nutritional factors in biochemical interactions that are part of an oncogenic process or inhibit free radical proliferation have attracted considerable interest in relation to molecular mechanism(s) and the natural history of human cancer. Epidemiologic and experimental studies have drawn attention to the association between dietary micronutrient deficiencies and the incidence of neoplastic and malignant lesions. In the last two decades, the role(s) of retinoids, carotenoids, tocopherols and water-soluble antioxidant vitamins, and allegations of anti-tumor properties in the daily dietary consumption of fresh fruits and green leafy vegetables, have captured the attention of an increasingly sensitive diet- and health care-conscious public, the biochemical community, and industrial food producers. Moreover, recent epidemiologic and compelling advances in molecular biology have linked the presence of restricted human papillomavirus (HPV) subtypes to cervical carcinoma and precursor lesions. In the present report, we identify and review measurable effects of dietary deficiencies of selected antioxidant micronutrients (i.e., beta-carotene and vitamins A, C, and E) and their association with known cervix cancer risk factors in the pathogenesis and potential prevention of cervix dysplasias, presumed to be the precursor lesions of cervix cancer.

Lipid-soluble antioxidants: beta-carotene and alpha-tocopherol levels in breast and gynecologic cancers.

Free radical-induced damage is etiologically implicated in many chronic diseases including cancer. Epidemiologic data suggest an association between increased dietary intake of nutrients that are high in antioxidant vitamins and protection against the incidence of some human cancers. The purpose of this study was (a) to determine whether specific tissue antioxidants (beta-carotene and alpha-tocopherol) and any differences in their levels were measurable in randomly selected human breast and gynecologic malignant neoplasms and nonneoplastic tissue samples obtained from the same patient and (b) to establish normal ranges of these two antioxidant levels in human female reproductive tract tissues. Tissue samples were excised immediately from surgical specimens and released by staff pathologists from a spectrum of human female cancers. Neoplastic and adjacent nonneoplastic tissues samples were obtained from the same patient. Normal reproductive tract tissue samples were obtained from women undergoing hysterectomy for benign gynecologic conditions. Breast carcinoma and adjacent nonmalignant tissue specimens were obtained from women undergoing mastectomy. The concentrations of beta-carotene and alpha-tocopherol were measured by high-pressure liquid chromatography. In the same patient, beta-carotene levels were significantly lower in the cervical (P < 0.01) and endometrial (P < 0.005) carcinoma tissues than the levels detectable in adjacent nonneoplastic sites. In contrast, beta-carotene levels were higher in the ovarian (P < 0.05), breast (P < 0.005), and vulva (P < 0.05) carcinoma tissues. The alpha-tocopherol concentrations were significantly higher in the cancer tissues of cervix (P < 0.01) and endometrium (P < 0.001) than those in adjacent noninvolved tissue sites. The tissue concentrations of alpha-tocopherol in malignant and adjacent normal sites in breast, ovary, and vulva were comparable. For the first time, the ranges for beta-carotene and alpha-tocopherol levels in the normal female reproductive tract tissues were also established. The present findings of contrasting tissue levels of the antioxidants (beta-carotene and alpha-tocopherol) in breast, cervix, endometrium, ovary, and vulva cancers and in nonneoplastic tissues of the same patient suggest an organ-specific and heterogenous distribution. These antioxidants appear to be essential nutritional requirements of the human female reproductive tract and breast and are implicated in the pathophysiology and carcinogenesis of these human organs. The findings require further study of the role of these antioxidant nutrients in epithelial cell proliferation, maturation, and differentiation.

Decreased beta-carotene levels in exfoliated vaginal epithelial cells in women with vaginal candidiasis.

PROBLEM: Women are more susceptible to vaginal candidiasis when the host immune response is suppressed. The antioxidant nutrient beta-carotene is postulated to possess immunoenhancing properties. The purpose of this study was to investigate beta-carotene concentrations in exfoliated vaginal epithelial (EVE) cells in women with vaginal candidiasis. METHODS: Beta-carotene levels in EVE cells, collected by a saline lavage technique from 22 women with vaginal candidiasis and 20 normal controls, were analyzed. The diagnosis of vaginal candidiasis was established by the presence of pruritus, white cheesy vaginal discharge, and a positive potassium hydroxide preparation. Beta-carotene levels were assayed using high pressure liquid chromatography. RESULTS: Vaginal cell concentrations of beta-carotene were significantly decreased in women with vaginal candidiasis (P < 0.001). CONCLUSIONS: Decreased beta-carotene levels, and possibly other antioxidants, may alter the local immune response resulting in disturbances in the vaginal flora, overgrowth of candida, and the development of vaginal candidiasis.

Preeclampsia and antioxidant nutrients: decreased plasma levels of reduced ascorbic acid, alpha-tocopherol, and beta-carotene in women with preeclampsia.

OBJECTIVE: Our purpose was to investigate the plasma levels of three potent antioxidant nutrients in women with preeclampsia. STUDY DESIGN: Fasting venous blood samples were collected from 30 women with preeclampsia and from 44 women with uncomplicated pregnancies. The criteria for recruitment included age 15 to 35 years, gestational age 28 to 42 weeks, singleton pregnancy, intact membranes, absence of labor contractions, and absence of any other medical complication concurrent with preeclampsia. Reduced ascorbic acid, alpha-tocopherol, and beta-carotene levels were assayed with high-pressure liquid chromatography. RESULTS: Plasma levels of reduced ascorbic acid were significantly decreased in patients with mild and severe preeclampsia (p < 0.01). Plasma alpha-tocopherol and beta-carotene levels were significantly decreased only in severe preeclampsia compared with controls (p < 0.05 and p < 0.05, respectively). CONCLUSION: In patients with preeclampsia antioxidant nutrients may be utilized to a greater extent to counteract free radical-mediated cell disturbances, resulting in a reduction in antioxidant plasma levels. Water-soluble antioxidant nutrients may initially be consumed, followed by lipid-soluble antioxidants.

Alterations in erythrocyte glutathione metabolism associated with cervical dysplasias and carcinoma in situ.

The study was designed to test the hypothesis whether cervical dysplasias of the more severe grades are associated with elevated erythrocyte glutathione levels. Subjects were women who obtained Pap tests and were subsequently found (1) not to have any cervical lesions or (2) to have colposcopically visualized, biopsy-confirmed cervical abnormalities histopathologically diagnosed as mild, moderate, severe dysplasias, or carcinoma in situ (CIS). The erythrocyte levels of reduced glutathione (GSH), oxidized glutathione (GSSG), glutathione reductase (GR), glucose-6-phosphate dehydrogenase (G6PD), and 6-phosphogluconate dehydrogenase (6PGD) were analyzed from coded peripheral venous blood samples. GSH and GR concentrations increased with increasing severity of dysplasia. Exploratory data analysis and multiple pairwise comparisons suggested comparable levels of the glutathione-related variables between these histopathological pairs: (1) mild and moderate dysplasias or (2) severe dysplasia and CIS. We suggest that the changes in erythrocyte glutathione-related indices in conjunction with histopathological diagnosis may have the potential to distinguish between low- and high-grade cervical dysplastic lesions.

Beta-carotene levels in exfoliated cervicovaginal epithelial cells in cervical intraepithelial neoplasia and cervical cancer.

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.

Factors influencing the exfoliation of cervicovaginal epithelial cells.

OBJECTIVE: Our objective was to investigate the association of smoking and exfoliation of cervicovaginal epithelial cells while controlling for other factors that may potentially influence cell exfoliation (e.g., presence of cervical intraepithelial neoplasia or koilocytes, the use of oral contraceptives, age, and the phase of the menstrual cycle). STUDY DESIGN: Cervicovaginal lavage specimens and epidemiologic questionnaires were obtained with informed consent from 190 women. The cervicovaginal lavage samples were processed to separate other contaminants. The number of squamous epithelial cells counted was expressed as cells per milliliter of lavage. RESULTS: Multiple linear regression analysis revealed that the number of exfoliated epithelial cells was significantly higher in smokers (p < 0.01) and also in women with cervical intraepithelial neoplasia (p < 0.05). The other studied variables had no detectable effect. CONCLUSION: The findings suggest that smoking or the presence of cervical intraepithelial neoplasia may induce an acceleration in the exfoliation of cervicovaginal epithelial cells. This may alter cell maturation and may be a factor in the oncogenic process.

Endogenous estradiol and progesterone concentrations in smokers on oral contraceptives.

The simultaneous effects of cigarette smoking and oral contraceptives on serum estradiol and progesterone levels were investigated in 114 premenopausal women. Serum 17 beta-estradiol and progesterone levels were measured by radioimmunoassay. In smokers, estradiol and progesterone levels were significantly lower (p less than 0.025). In smokers using oral contraceptives, estradiol and progesterone levels were the lowest (p less than 0.001 and p less than 0.01, respectively). The findings suggest that smoking and oral contraceptives independently lower serum estradiol and progesterone concentrations in premenopausal women and that the effects may be additive.

Plasma ascorbic acid and beta-carotene levels in women evaluated for HPV infection, smoking, and cervix dysplasia.

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.

Plasma levels of antioxidant beta-carotene and alpha-tocopherol in uterine cervix dysplasias and cancer.

Chronic human health problems, namely arteriosclerosis, myocardial ischemia, and cancer, may be caused by highly active oxygen species and may be preventable by antioxidant vitamins. In humans, the sources of two major antioxidants, beta-carotene and alpha-tocopherol, are dietary. In this study, we measured the plasma concentrations of beta-carotene and alpha-tocopherol by reverse-phase high-pressure liquid chromatography in a cross-sectional sampling of 116 women. Significantly reduced plasma levels of beta-carotene and alpha-tocopherol were observed in women with histopathologically diagnosed cervical dysplasias or cancer (p less than 0.0001 and p less than 0.005, respectively). There was an inverse association between the plasma levels of both beta-carotene and alpha-tocopherol and increasingly severe graded cervical histopathology. In groups with advanced dysplasias, the percentage of smokers was markedly increased and the women were comparatively older (p less than 0.0001). A strong association was noted between smoking status and plasma beta-carotene levels, independent of cervical pathology. However, this was not evident with respect to alpha-tocopherol. The findings suggest that the antioxidants beta-carotene and alpha-tocopherol have biologic functions that are interdependent in the pathogenesis of cervical intraepithelial lesions and cervical cancer.