Hormonal content and potency of oral contraceptives and breast cancer risk among young women

Recent use of oral contraceptive pills is associated with a modest risk of breast cancer among very young women. In this US population-based case-control study, we evaluated whether the excess risk associated with recent oral contraceptive use is ubiquitous for all pill types or attributable to specific oral contraceptive preparations. Hormonal content and potency of combination oral contraceptives used for the longest duration within 5 years of interview for breast cancer cases aged 20-44 years (N=1640) were compared with age-matched community controls (N=1492). Women who recently used oral contraceptives containing more than 35 microg of ethinyl oestradiol per pill were at higher risk of breast cancer than users of lower dose preparations when compared to never users (respective relative risks of 1.99 and 1.27, P(trend)<0.01). This relationship was more marked among women <35 years of age, where risks associated with high- and low-dose ethinyl oestradiol use were 3.62 and 1.91 (P(trend)<0.01), respectively. We also found significant trends of increasing breast cancer risk for pills with higher progestin and oestrogen potencies (P(trend)<0.05), which were most pronounced among women aged <35 years of age (P(trend)<0.01). Risk was similar across recently used progestin types. Our findings suggest that newer low-potency/low oestrogen dose oral contraceptives may impart a lower risk of breast cancer than that associated with earlier high-potency/high-dose preparations.     

Oral contraceptives and prognosis of breast cancer in women aged 35 to 50

Among 193 breast cancer patients aged 35-50 years, there was no appreciable difference in the extent of disease at diagnosis between 53 oral contraceptive (OC) users and 140 OC non-users. There was no overall significant difference between OC users and non-users for either the disease-free interval (P = .81), metastatic period (P = .41), or survival (P = .79), either alone or when adjusted for stage or family history. The survival rate of OC users of more than 2 years was similar to the survival rate of those of shorter duration (P = .36). Patients who began the use of OC 10 years or more before diagnosis showed no statistical difference from those beginning more recently (P = .69). Recent OC users within a year of diagnosis had a survival rate similar to that of other users who stopped the pills at least 1 year prior to diagnosis (P = .14). Our data suggest no adverse effects of OC use on the prognosis of breast cancer, regardless of duration of use, latency or recency period.     

The association between oral contraceptive use and lobular and ductal breast cancer in young women

Recent reports indicate that the incidence of lobular breast cancer is increasing at a faster rate than ductal breast cancer, which may be due to the differential effects of exogenous hormones by histology. To address this issue, we examined whether the relationship between oral contraceptive use and incident breast cancer differs between lobular and ductal subtypes in young women. A population-based sample of in situ and invasive breast cancer cases between ages 20 and 44 were recruited from Atlanta, GA; Seattle-Puget Sound, WA and central New Jersey. Controls were sampled from the same areas by random-digit dialing, and were frequency matched to the expected case age distribution. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated using polytomous logistic regression. Among the 100 lobular cancers, 1,164 ductal cancers, and 1,501 controls, the odds ratios for oral contraceptive ever use were 1.10 (95% CI = 0.68-1.78) for lobular cancers and 1.21 (95% CI = 1.01-1.45) for ductal cancers, adjusted for study site, age at diagnosis, and pap screening history. Our results suggest that the magnitude of the association between ever use of oral contraceptives and breast cancer in young women does not vary strongly by histologic subtype. These results are similar to previous studies that report little difference in the effect of oral contraceptive use on breast cancer by histology.     

Use of oral contraceptives and endometrial cancer risk (Sweden)

Objectives: To estimate the magnitude and persistence of the protective effect of use of combined oral contraceptives (COCs) and endometrial cancer risk.Methods: We performed a nation-wide, population-based case–control study among postmenopausal women aged 50–74 years in Sweden, which included 709 subjects with incident, histopathologically verified endometrial cancer, and 3,368 controls with an intact uterus. We used unconditional logistic regression to calculate odds ratios as estimates of relative risks.Results: Use of any sort of oral contraceptive decreased risk for endometrial cancer by 30%, while progestin-only pills reduced risk more markedly. For COCs the reduction in risk was noticeable following 3 or more years of use (OR 0.5, 95% CI 0.3–0.7), and increased with duration of intake, reaching 80% lower risk after 10 years of use. The protective effect of COC use was similar for all degrees of tumor differentiation and invasiveness, and remained for at least 20 years after cessation of use. Subsequent use of hormone replacement did not modify these protective effects.Conclusions: We conclude that COC use confers a long-lasting protection against endometrial cancer risk which is particularly marked for long-term users.(institution where the work has been performed)     

Catechol-O-Methyltransferase (COMT) gene polymorphism and breast cancer risk in young women

Oestrogen exposure has long been considered to be a main risk factor of breast cancer. More recently, interest has also focused on the possible carcinogenic influence from oestrogen metabolites, such as catechol oestrogens. O-methylation, catalysed by Catechol-O-Methyltransferase (COMT), is one pathway by which the potentially carcinogenic catechol oestrogens can be inactivated. The gene coding for COMT protein contains a single-nucleotide polymorphism (SNP), resulting in an amino acid shift Val-->Met, which has been shown to determine high- and low-activity configuration of the enzyme. We hypothesized that the low-activity allele, COMT(Met), may be implicated in early onset breast cancer. In the present case-control study, including 126 young breast cancer patients (相似文献   

Progestogen-only oral contraceptives and risk of breast cancer in New Zealand

Little is known about the influence of progestogen-only contraceptives on a woman's risk of breast cancer. This issue was examined in a national population-based case-control study in New Zealand. A total of 891 women aged 25 to 54 years with a first diagnosis of breast cancer and 1,864 control subjects, randomly selected from the electoral rolls, were interviewed. Use of progestogen-only pills was reported by 8.7 percent of all control subjects (and by 17.3 percent of those aged 25 to 34 years). The relative risk (RR) of breast cancer in women who had ever used progestogen-only pills was estimated to be 1.1 (95 percent confidence interval [CI]=0.73–1.5). In women aged 25 to 34 years, the RR was 2.3 (CI=1.2–4.3). Women who had started using progestogen-only pills within the last 10 years were at increased risk of breast cancer (RR=1.6, CI=1.0–2.4), whereas those who had first used them earlier were at significantly reduced risk (RR=0.44, CI=0.22–0.90). These findings are similar to results for depot medroxyprogesterone acetate, and a possible analogy with the influence of pregnancy is also suggested.The anthors are with the Department of Preventive and Social Medicine, University of Otago, Dunedin, New Zealand. Address correspondence to: Dr Skegg, Department of Preventive and Social Medicine, University of Otago Medical School, P. O. Box 913, Dunedin, New Zealand. This research was supported by grants from the Medical Research Council of New Zealand and from the Special Program of Research, Development, and Research Training in Human Reproduction, World Health Organization.     

Hypotheses: Melatonin/steroid combination contraceptives will prevent breast cancer

Summary The use of the conventional combination oral contraceptives (containing ethinyl-estradiol and a progestin) is associated with reduced risk of ovarian and endometrial cancer. However, prolonged use of these pills before first term pregnancy apparently increases the risk of pre menopausal breast cancer. We propose that the pineal gland hormone melatonin, combined with a progestin, as a new and novel oral contraceptive combination might prevent breast cancer in long term users. This hypothesis is based on the assumption that women have a propensity to develop breast cancer which correlates with number of ovulatory cycles over their lifetime. In evolution, the phylogenetic point at which women became sensitive to breast cancer evolved at a transfer point of the mechanism of ovulation from seasonal ovulation, which is still common in many mammalian species, to the current human pattern of continuous ovulatory cycles. We suggest that melatonin/ovariansteroid contraceptive will restore the lost mechanism of endogenous anovulation, and thus, by preventing continuous epithelial breast cell proliferation, will reduce the risk of breast cancer in long-term users.     

The patched polymorphism Pro1315Leu (C3944T) may modulate the association between use of oral contraceptives and breast cancer risk

The gene coding for the human homologue of the Drosophila segment polarity gene patched (PTCH1) is mutated in several common human tumors. In mice, haplodeficiency at the Ptch1 locus results in severe histologic defects in mammary ductal structure. We found no mutations within the coding region of PTCH1 in 17 human primary breast carcinomas. However, the biallelic Pro1315Leu (C3944T) polymorphism of PTCH1 was significantly associated with breast cancer in 41 Bavarian patients compared to 85 healthy controls. We investigated whether this variant influences susceptibility for breast cancer in 611 breast cancer patients diagnosed by age 50 years and 1,057 controls matched by age and study region in Germany and in 1,093 breast cancer patients from the United Kingdom. Allele and genotype frequencies were not different between cases and controls. However, multivariate logistic regression analysis revealed an effect modification of oral contraceptive use (OC) on breast cancer risk by Leu-carrier status. Compared to women who have Pro/Pro and never used OC, Pro/Pro OC users had an increased odds ratio for breast cancer of 1.7. The odds ratio was also 1.7 for Leu-carriers who never used OC, but this was attenuated among Leu-carriers who ever used OC by 20%. The gene-environmental interaction was confirmed in case-only analysis of the German and British studies, yielding an interaction odds ratio of 0.7 for premenopausal women (p = 0.06). Longer duration of pill use was associated with a significantly greater risk reduction (p for trend = 0.015). Our novel observation of a differential effect of OC use on breast cancer risk by PTCH1 1315Leu-carrier status suggests the interesting possibility of the Sonic hedgehog/Patched (SHH/PTCH1) signaling pathway being involved in hormone-induced development of breast carcinoma.     

Oral contraceptive use and breast cancer risk among African-American women

Recent epidemiologic studies, most of them in predominantly White populations, have suggested that long duration of oral contraceptive (OC) use may increase the risk of breast cancer at young ages. We assessed the relationship of OC use to the risk of breast cancer in African-American women aged 25 to 59 years, using interview data from a multipurpose hospital-based case-control study. Five hundred and twenty-four cases hospitalized for invasive breast cancer were compared with 1,021 controls with nonmalignant conditions unrelated to OC use. Relative risks (RR) and 95 percent confidence intervals (CI) were estimated relative to a reference category of use for less than 12 months; potential confounders were controlled by multiple logistic regression analysis. Among women under age 45, three or more years of OC use was associated with an increased risk of breast cancer: the RR estimate was 2.8 (CI=1.5–5.0) for three to four years of use, and declined to 1.5 (CI=0.8.3.0) for 10 or more years of use. Recency and timing of use did not explain the observed association. Among women aged 45 to 59, OC use was associated with little or no increase in risk: the RR estimate for three or more years of use was 1.3 (CI=0.7–2.4). The findings add to the evidence from studies of White women and a recent study of Black women which have suggested an increased risk of breast cancer at young ages for moderate or long duration use of OCs.This research was supported by the US National Cancer Institute (grants R01 CA55766 and R01 CA45762). Additional support was provided by the US Food and Drug Administration (FD-U-000082); the views expressed do not necessarily represent the views of the Food and Drug Administration. The Slone Epidemiology Unit also receives support from Hoffmann-La Roche, Inc., and Marion Merrell Dow Inc.     

Previous oral contraceptive use and breast cancer risk according to hormone replacement therapy use among postmenopausal women

Objective To assess postmenopausal breast cancer risk in relation to particular patterns of oral contraceptive (OC) use according to hormone replacement therapy (HRT) exposure.Methods Time-dependent Cox regression models were used to analyse information on postmenopausal women from a large-scale French cohort. Among a total of 68,670 women born between 1925 and 1950, 1405 primary invasive postmenopausal breast cancer cases were identified from 1992 to 2000.Results A non-significant decrease in risk of around 10% was associated with ever OC use as compared to never OC use in postmenopausal women. No significant interaction was found between OC and HRT use on postmenopausal breast cancer risk. Breast cancer risk decreased significantly with increasing time since first OC use (test for trend: p=0.01); this was consistent after adjustment for duration of use or for time since last use.Conclusion No increase in breast cancer risk was associated with previous OC exposure among postmenopausal women, probably because the induction window had closed. Some women may develop breast cancer soon after exposure to OCs, leading to a deficit of cases of older women. Further investigation is therefore required to identify young women at high risk.* Address correspondence to: F. Clavel-Chapelon, Equipe E3N-EPIC, INSERM “Nutrition, Hormones, Cancer”, Institut Gustave-Roussy, 94805 – Villejuif, France.     

Progestin‐only and combined oral contraceptives and receptor‐defined premenopausal breast cancer risk: The Norwegian Women and Cancer Study

Receptor‐defined subtypes of breast cancer represent distinct cancer types and have differences in risk factors. Whether the two main hormonal forms of oral contraceptives (OCs); i.e. progestin‐only (POC) and combined oral contraceptives (COC), are differentially associated with these subtypes are not well known. The aim of our study was to assess the effect of POC and COC use on hormone receptor‐defined breast cancer risk in premenopausal women in a prospective population‐based cohort – The Norwegian Women and Cancer Study (NOWAC). Information on OC use was collected from 74,862 premenopausal women at baseline. Updated information was applied when follow‐up information became available. Multiple imputation was performed to handle missing data, and multivariable Cox regression models were used to calculate hazard ratios (HR) for breast cancer. 1,245 incident invasive breast cancer cases occurred. POC use ≥5 years was associated with ER+ (HR = 1.59, 95% CI 1.09– 2.32, p_trend = 0.03) and ER+/PR+ cancer (HR = 1.63, 95% CI 1.07–2.48, p_trend = 0.05), and was not associated with ER? (p_{heterogeneity} = 0.36) or ER?/PR? (p_{heterogeneity} = 0.49) cancer. COC use was associated with ER? and ER?/PR? cancer, but did not increase risk of ER+ and ER+/PR+ cancer. Current COC use gave different estimates for ER/PR‐defined subtypes (p_{heterogeneity} = 0.04). This is the first study to show significant associations between POC use and hormone receptor‐positive breast cancer. The lack of power to distinguish effects of POC use on subtype development calls for the need of larger studies to confirm our finding.     

Breast cancer and specific types of oral contraceptives: a large Norwegian cohort study

The aim of our study was to examine the risk of breast cancer according to specific types of estrogens and progestagens in oral contraceptives (OCs) based on the prospective Norwegian Women and Cancer study (NOWAC). Between 1991-97 women aged 30-70 years were drawn at random from the central person register and mailed an invitation and a questionnaire. Women (102,443) were enrolled with follow-up information collected throughout 1999 by linkage with national registries of cancer, mortality and emigration based on the unique national identification number. Among the 96,362 women included in the present analysis 851 invasive breast cancer were diagnosed. The adjusted risk of breast cancer increased with 25% for ever use of OCs and the risk increased with increasing duration of use (test for trend: p = 0.007). No association between time since last use and breast cancer risk was found after stratification on duration of use. Positive trend was still found for total duration of use among women who used OCs more than 5 years ago. Second generation of OCs had an increased risk with increasing duration of use. Classifying progestagens according to chemical groups, the relative risk increased significantly with increasing cumulative dose of levonorgestrel progestagen. It was difficult to conclude for the other groups due to lack of power. In a multivariate analysis the cumulative dose for all progestagen groups were non-significant, although we observed a significant increased risk with increasing milligram-months of estrogen exposure (p = 0.002). In conclusion, the increased risk of breast cancer related with OC formulations could be due mostly to estrogen component.     

Recent oral contraceptive use and risk of breast cancer (United States)

We examined the association between recent oral contraceptive (OC) use and the risk of breast cancer in data from a large population-based case-control study in the United States. Cases (n=6,751) were women less than 75 years old who had breast cancer identified from statewide tumor registries in Wisconsin, Massachusetts, Maine, and New Hampshire. Controls (n=9,311) were selected randomly from lists of licensed drivers (if aged under 65 years) and from lists of Medicare beneficiaries (if aged 65 through 74 years). Information on OC use, reproductive experiences, and family and medical history was obtained by telephone interview. After adjustment for parity, age at first delivery, and other risk factors, women who had ever used OCs were at similar risk of breast cancer as never-users (relative risk [RR]=1.1, 95 percent confidence interval [CI]=10–1.2). Total duration of usealso was not related to risk. There was a suggestion that more recent use was associated with an increased risk of breast cancer; use less than two years ago was associated with an RR of 1.3 (CI=0.9–1.9). However, only among women aged 35 to 45 years at diagnosis was the increase in risk among recent users statistically significantly elevated (RR=2.0, CI=1.1–3.9). Use prior to the first pregnancy or among nulliparous women was not associated with increased risk. Among recent users of OCs, the risk associated with use was greatest among non-obese women, e.g., among women with body mass index (kg/m²) less than 20.4, RR=1.7, CI=1.1–2.8. While these results suggest that, in general, breast cancer risk is not increased substantially among women who have used OCs, they also are consistent with a slight increased risk among subgroups of recent users.Authors are with the University of Wisconsin Comprehensive Cancer Center, Madison, WI, USA (Dr Newcomb, Ms Trentham Dietz); NIEHS Epidemiology Branch, Research Triangle Park, NC (Dr Longnecker); Fred Hutchinson Cancer Research Center, Seattle, WA (Dr Surer); Department of Obstetrics and Gynecology, Pritzker School of Medicine, The University of Chicago, Chicago, IL (Dr Mittendorf); Department of Community and Family Medicine, Dartmouth Medical School, Hanover, NH (Dr Baron); Boston University, School of Public Health, Boston, MA (Dr Clapp); Department of Epidemiology and Department of Nutrition, Harvard School of Public Health, and Channing Laboratory, Harvard Medical School and Department of Medicine, Brigham and Women's Hospital, Boston, MA (Dr Willett). Address correspondence to: Dr Polly A. Newcomb, University of Wisconsin-Madison Comprehensive Cancer Center, 1300 University Ave., #4780, Madison, WI 53706, USA. Supported by Public Health Service (National Cancer Institute) grants R01 CA 47147 and R01 CA 47305.     

Oral contraceptives and the risk of endometrial cancer

The relationship between the use of combbination oral contraceptives (OCs) and the risk of endometrial cancer was assessed in a case-control study conducted in the Swiss Canton of Vaud between 1 January 1988 and 31 July 1990. Subjects included 122 women aged 75 or less with histologically confirmed endometrial cancer, and 309 control women in hospital for acute conditions unrelated to OC use. Overall, 14 percent of cases and 27 percent of controls had ever used OCs, corresponding to a multivariate relative risk (RR) of 0.5 (95 percent confidence interval [CI]: 0.3. 0.8). The risk of endometrial cancer was found to be related inversely to duration of OC use: RR=1.0 for less than two years of OC use; 0.5 for two to five years; and 0.3 (95 percent CI: 0.1, 0.7) for more than five years. The protection appeared greater within 20 years since last use, and the RR rose to 0.8 after 20 or more years since last use; numbers are too small, however, for reliable inference from these subanalyses. No significant interaction or modifying effect was observed with other major factors related to endometrial cancer, including parity, body mass index, estrogen replacement therapy, and cigarette smoking. While this study provides further evidence for the protective effect of OCs against risk of endometrial cancer, the relationship requires continued evaluation to assess the long-term implications and public health impact of OC use.This work was supported in part by the Swiss National Science Foundation Grant No. 3.866-0.88.     

Combined effect of oral contraceptive use and hormone replacement therapy on breast cancer risk in postmenopausal women

OBJECTIVE: We examined breast cancer risk related to lifetime exposure to oral contraceptives (OCs) and hormone replacement therapy (HRT) in postmenopausal women. METHODS: The Women's Contraceptive and Reproductive Experiences (CARE) Study was a population-based case-control study that included 1847 postmenopausal women with incident invasive breast cancer, and 1932 control subjects, identified using random digit dialing. RESULTS: 45% of cases and 49% of controls used both OCs and HRT. OC users were not at increased risk regardless of subsequent HRT exposure. HRT users who had used OCs previously did not have a higher risk of breast cancer than women with no exposure to OCs. We observed a negative interaction (p-value: 0.032) of combined hormone replacement therapy (CHRT) and past OC use. The increase in risk with CHRT was stronger in women who had never used OCs in the past (odds ratio: 1.05; 95% confidence interval: 1.01-1.10 per year of exclusive CHRT use) than in women who had used OCs (odds ratio: 1.00; 95% confidence interval: 0.97-1.03). CONCLUSIONS: We found no indication that adverse effects of exposure to OCs or HRT appeared only in the presence of the other hormone or were exacerbated by exposure to the other hormone.     

Hepatomas in young women on oral contraceptives: report of two cases and review of the literature

Hepatocellular carcinoma (HCC) developed in two women who had ingested oral contraceptives for prolonged duration. One of the patients had hepatoma restricted to the liver, and it was successfully resected. The other patient presented with metastatic HCC to the sacrum and lung, and she died after an initial response to chemotherapy in 12 months. Review of literature showed 23 previously reported cases of HCC associated with "pill" use since 1973. Although the reported instances of HCC in pill users are few in number, the majority of affected females were in their 20s and early 30s, without any preexisting liver disease. Even though the risk of developing HCC on oral contraceptives is low, this association adds to the list of complications induced by oral contraceptives in premenopausal women. Two cases are reported and literature reviewed.     

Reproductive risk factors and oestrogen/progesterone receptor-negative breast cancer in the Breast Cancer Family Registry

Background:

Oestrogen receptor (ER)- and progesterone receptor (PR)-negative (ER−PR−) breast cancer is associated with poorer prognosis compared with other breast cancer subtypes. High parity has been associated with an increased risk of ER−PR− cancer, but emerging evidence suggests that breastfeeding may reduce this risk. Whether this potential breastfeeding benefit extends to women at high risk of breast cancer remains critical to understand for prevention.

Methods:

Using population-based ascertained cases (n=4011) and controls (2997) from the Breast Cancer Family Registry, we examined reproductive risk factors in relation to ER and PR status.

Results:

High parity (⩾3 live births) without breastfeeding was positively associated only with ER−PR− tumours (odds ratio (OR)=1.57, 95% confidence interval (CI), 1.10–2.24); there was no association with parity in women who breastfed (OR=0.93, 95% CI 0.71–1.22). Across all race/ethnicities, associations for ER−PR− cancer were higher among women who did not breastfeed than among women who did. Oral contraceptive (OC) use before 1975 was associated with an increased risk of ER−PR− cancer only (OR=1.32, 95% CI 1.04–1.67). For women who began OC use in 1975 or later there was no increased risk.

Conclusions:

Our findings support that there are modifiable factors for ER−PR− breast cancer and that breastfeeding in particular may mitigate the increased risk of ER−PR− cancers seen from multiparity.     

Oral contraceptive use and the prognosis of breast cancer

Summary In 471 breast cancer patients the influence of a positive history of oral contraceptive (OC) use on survival was investigated. 297 (63%) patients used OCs during any period of their life and 92 (20%) used them still at the time of diagnosis. Sixty months after diagnosis OC users had a significantly increased overall survival (p = 0.037). Survival rates amounted to 79.5% and 70.3% for OC users and non-users, respectively. The effect persisted after adjustment for other prognostic factors and was mainly attributed to women who had taken OCs four years or longer (p = 0.025). Comparing the survival after a 56 months median follow-up dependent on duration of OC use (never, 1–48 months, 49 months) in subgroups of prognostic factors, the most significant influence on survival was observed among long-term users with tumors more than 2 cm in diameter (p = 0.005), with axillary node-positive tumors (1–3 nodes, p = 0.055/ 4 nodes, p = 0.019), and with tumors of low estrogen receptor (p = 0.015) or progesterone receptor content (p = 0.04). The difference in survival between OC users and non-users cannot be explained by the distribution of prognostic factors investigated (histological type, histological grade, tumor size, lymph node involvement, hormonal receptor content). OC users had an even higher percentage of poorly differentiated tumors (p = 0.003). These results suggest an effect of OC use on tumor biology during the preclinical phase of the disease.     

Breast cancer family history as a risk factor for early onset breast cancer

Summary Since full breast cancer screening is not generally recommended for young women, it is important to identify individuals who are at higher risk for early onset breast cancer. We investigated the relationship between age of onset of breast cancer in 328 probands (consecutively ascertained patients from our oncology clinic) and breast cancer incidence and age of onset in their female relatives. We found that a family history of early onset breast cancer was associated with higher risk of early onset breast cancer. A family history of early onset breast cancer occurred more frequently among young (<40) breast cancer probands than among older (40) breast cancer probands (p<0.001; OR = 23). This relationship was particularly evident when the analysis was restricted to thehereditary breast cancer probands (p<0.001; OR = 44). We also observed a positive family history of breast cancer (any age) more frequently in young breast cancer probands than in older breast cancer probands (p<0.001; OR = 2.8). These observations have important pragmatic implications for surveillance. We recommend intense surveillance for breast cancer, initiated earlier, for women with close relatives diagnosed with early onset breast cancer.     

Human papillomavirus infection and use of oral contraceptives

Human papillomavirus (HPV) infection is thought to be a necessary but not sufficient cause of most cases of cervical cancer. Since oral contraceptive use for long durations is associated with an increased risk of cervical cancer, it is important to know whether HPV infection is more common in oral contraceptive users. We present a systematic review of 19 epidemiological studies of the risk of genital HPV infection and oral contraceptive use. There was no evidence for a strong positive or negative association between HPV positivity and ever use or long duration use of oral contraceptives. The limited data available, the presence of heterogeneity between studies and the possibility of bias and confounding mean, however, that these results must be interpreted cautiously. Further studies are needed to confirm these findings and to investigate possible relations between oral contraceptive use and the persistence and detectability of cervical HPV infection.