Sexual behavior, condom use, and human papillomavirus: pooled analysis of the IARC human papillomavirus prevalence surveys.

Human papillomavirus (HPV) is a sexually transmitted infection but it is unclear whether differences in transmission efficacy exist between individual HPV types. Information on sexual behavior was collected from 11 areas in four continents among population-based, age-stratified random samples of women of ages > or = 15 years. HPV testing was done using PCR-based enzyme immunoassay. Unconditional logistic regression was used to estimate odds ratios (OR) of being HPV positive and corresponding 95% confidence intervals (95% CI). Variables were analyzed categorically. When more than two groups were compared, floating confidence intervals were estimated by treating ORs as floating absolute risks. A total of 11,337 women (mean age, 41.9 years) were available. We confirmed that lifetime number of sexual partners is associated with HPV positivity (OR for > or = 2 versus 1, 1.86; 95% CI, 1.63-2.11) but the association was not a linear one for HPV18, 31, and 33 (i.e., no clear increase for > or = 3 versus 2 sexual partners). Women who had multiple-type infection and high-risk HPV type infection reported a statistically nonsignificant higher number of sexual partners than women who had single-type and low-risk type infections, respectively. Early age at sexual debut was not significantly related to HPV positivity. Husband's extramarital sexual relationships were associated with an OR of 1.45 (95% CI, 1.24-1.70) for HPV positivity in their wives after adjustment for age and lifetime number of women's sexual partners. We did not observe a significant association with condom use. Our study showed an effect of both women's and their husbands' sexual behavior on HPV positivity. Furthermore, it suggests some differences in the pattern of the association between sexual behavior and different HPV types.     

Smoking, diet, pregnancy and oral contraceptive use as risk factors for cervical intra-epithelial neoplasia in relation to human papillomavirus infection

Smoking, nutrition, parity and oral contraceptive use have been reported as major environmental risk factors for cervical cancer. After the discovery of the very strong link between human papillomavirus (HPV) infection and cervical cancer, it is unclear whether the association of these environmental factors with cervical cancer reflect secondary associations attributable to confounding by HPV, if they are independent risk factors or whether they may act as cofactors to HPV infection in cervical carcinogenesis. To investigate this issue, we performed a population-based case-control study in the Vasterbotten county of Northern Sweden of 137 women with high-grade cervical intra-epithelial neoplasia (CIN 2-3) and 253 healthy age-matched women. The women answered a 94-item questionnaire on diet, smoking, oral contraceptive use and sexual history and donated specimens for diagnosis of present HPV infection (nested polymerase chain reaction on cervical brush samples) and for past or present HPV infections (HPV seropositivity). The previously described protective effects of dietary micronutrients were not detected. Pregnancy appeared to be a risk factor in the multivariate analysis (P < 0.0001). Prolonged oral contraceptive use and sexual history were associated with CIN 2-3 in univariate analysis, but these associations lost significance after taking HPV into account. Smoking was associated with CIN 2-3 (odds ratio (OR) 2.6, 95% confidence interval (CI) 1.7-4.0), the effect was dose-dependent (P = 0.002) and the smoking-associated risk was not affected by adjusting for HPV, neither when adjusting for HPV DNA (OR 2.5, CI 1.3-4.9) nor when adjusting for HPV seropositivity (OR 3.0, CI 1.9-4.7). In conclusion, after taking HPV into account, smoking appeared to be the most significant environmental risk factor for cervical neoplasia.     

The association of hormonal contraceptive use and HPV prevalence

Women diagnosed with cervical cancer report longer duration and more recent use of combined oral contraceptives (COCs). It is unclear whether COC use is associated with upstream events of human papillomavirus (HPV) infection prior to development of clinical disease. The objective of our study was to assess the association of contraceptive use on the risk for prevalent HPV infection in a cohort of long‐term hormonal contraceptive (HC) users. One thousand and seventy (n = 1,070) HIV‐negative women aged 20–37 from Thailand enrolled in a prospective study of the natural history of HPV. Baseline HPV genotype information, recency and duration of HC use, sexual behavior, other sexually transmitted infection (STI) information and cervical cytology and histology were assessed. At enrollment, 19.8% and 11.5% of women were infected with any HPV or any high‐risk (HR)‐HPV, respectively. After adjustment for age, current and past sexual risk behaviors, STI history and cytology, the use of COCs for >6 years was found to be associated with an increased risk of infection with any HPV [prevalence ratio (PR): 1.88 (1.21, 2.90)] and any HR‐HPV [PR: 2.68 (1.47, 4.88)] as compared to never users. Recent, long‐term COC use was associated with an increased risk for prevalent HPV infection independent of sexual behavior and cervical abnormalities. No similar association was observed for recent or long duration use of progestin‐only contraceptives (i.e., depomedroxyprogesterone acetate). These data suggest that COC use may impact early upstream events in the natural history of HPV infection.     

A pooled analysis of 10 case-control studies of melanoma and oral contraceptive use

Data regarding the effects of oral contraceptive use on women's risk of melanoma have been difficult to resolve. We undertook a pooled analysis of all case-control studies of melanoma in women completed as of July 1994 for which electronic data were available on oral contraceptive use along with other melanoma risk factors such as hair colour, sun sensitivity, family history of melanoma and sun exposure. Using the original data from each investigation (a total of 2391 cases and 3199 controls), we combined the study-specific odds ratios and standard errors to obtain a pooled estimate that incorporates inter-study heterogeneity. Overall, we observed no excess risk associated with oral contraceptive use for 1 year or longer compared to never use or use for less than 1 year (pooled odds ratio (pOR)=0.86; 95% CI=0.74-1.01), and there was no evidence of heterogeneity between studies. We found no relation between melanoma incidence and duration of oral contraceptive use, age began, year of use, years since first use or last use, or specifically current oral contraceptive use. In aggregate, our findings do not suggest a major role of oral contraceptive use on women's risk of melanoma.     

Oral contraceptive use, human papillomavirus infection, and risk of early cytological abnormalities of the cervix

Oral contraceptive (OC) use was examined as a risk factor for cytological abnormalities of the cervix among 1964 women receiving Papanicolaou smears at three hospitals in the Washington, D.C., area. A single pathologist classified cytological results from all women as normal (n = 1423), atypia (n = 314), low grade squamous intraepithelial lesion (SIL; n = 208), or high grade SIL (n = 19). Women in each of the three abnormal groups were compared to women with normal cytological diagnoses. A subset of 579 patients, including most of the women with low or high grade SIL and a matched group of controls, was tested for human papillomavirus (HPV) by type-specific Southern blot hybridization to examine the effects of OC use while taking into account the effects of HPV infection. OC use was found to be unrelated to risk of atypia or low grade SIL but was associated with an elevated risk of high grade SIL that increased with longer duration of use (relative risk = 4.6, 95% confidence interval = 1.1-18.1 for greater than or equal to 5 years of use). HPV infection was associated, as expected, with risk of low and high grade SIL but not with atypia. Taking the HPV results into consideration did not alter the OC findings. There was no evidence that OC use synergistically increased the risk of cervical neoplasia among HPV-infected women, although small numbers prevented a reliable evaluation for high grade SIL. OC use did appear to increase the detection of HPV types 16/18, but the etiological importance of this finding is unclear.     

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.     

The prevalence of human papillomavirus infection in Mombasa,Kenya

Objectives  

A human papillomavirus (HPV) prevalence survey was done in Mombasa, Kenya, to improve the knowledge of HPV prevalence and genotype distribution in sub-Saharan African countries overall, and in women of different ages.     

Cellular manifestations of human papillomavirus infection in the oral mucosa.

BACKGROUND AND OBJECTIVES: Human papillomavirus infection has been suggested to play a role in the development of epithelial carcinomas, particularly those of the uterine cervix. Less information is available on the role of the virus in oral lesions. It has been proposed that the viral oncoproteins specifically complex with the products of cellular tumor suppressor gene, namely E6 with p53 and E7 with retinoblastoma gene product. Inactivation or mutation in p53 gene is also known to result in loss of control over the cell cycle and increases in tumor proliferation rates. The present study examines the role of HPV infection in relation to p53 and the extent of the tumor proliferative compartment reflected by cyclin D1 and Ki-67 expression during various phases of tumor progression in the oral epithelium. METHOD: Nonisotopic in situ hybridization (NISH) was performed to detect HPV 6/11 and 16/18. Expression of p53, cyclin D1, Ki-67, and the HPV 16/18 E6 protein were detected by immunocytochemistry. RESULTS: There was significant correlation between the extent of histological abnormality and HPV infection. A correlation (r = 0.250, P = 0.0089) was evident between the presence of HPV 16 and occurrence of invasive cancer. Expression of the tumor suppressor p53 protein also showed significant positive correlation with histology (r = 0.475, P = 0.00004). The tumor proliferative fraction also increased with the extent of histological abnormality (r = 0.387, P = 0.0003 for cyclin D1 and r = 0.463, P = 0.0001 for Ki 67). Accumulation of p53 and increase in tumor proliferation also correlated to the presence of HPV infection (r = 0.511, P = 0.00003 for p53; r = 0.478, P = 0.00002 for cyclin D1 and r = 0.521, P = 0.00004 for Ki-67). CONCLUSIONS: The present study thus demonstrates the importance of HPV infection in oral tissue. Expression of the high-risk HPV 16/18 E6 protein also appears to be a critical event along with aberrant p53 expression. These results are of significance to the molecular epidemiology of oral cancer and may also be used to supplement and elaborate the diagnosis of oral lesions.     

PCR-detected genital papillomavirus infection: prevalence and association with risk factors for cervical cancer.

In an investigation conducted in student health clinic patients, the polymerase chain reaction was used to detect human papillomavirus (HPV) DNA, thereby allowing measurement of the prevalence of HPV infection and study of the association between HPV infection and risk factors for cervical cancer. Of 159 women eligible to participate, 105 (66%) provided a specimen of cervical cells for HPV typing, and also answered an interviewer-administered questionnaire which sought information on risk factors for cervical cancer. Nucleic acid extracted from cervical cells was screened with primers for HPV types 6, 11, 16, 18, 33 and with an HPV Consensus primer. Overall, the prevalence of HPV infection was 18.1%, while for HPV-6/11 it was 2.9% and for HPV-16/18 it was 10.5%. There were statistically significant increases in risk of HPV infection with a history of ever having smoked cigarettes (overall, and for HPV-16 alone) and with a history of usually having sexual intercourse during menstrual periods (overall, but not for HPV-16), and these associations were independent of the effects of age at first sexual intercourse and number of sexual partners. The latter 2 variables, as well as the total number of occasions of sexual intercourse, a history of anal intercourse, and a history of ever having used oral contraceptives, were not associated with statistically significant alterations in risk of HPV infection.     

Human papillomavirus and long-term oral contraceptive use increase the risk of adenocarcinoma in situ of the cervix.

We examined United States Surveillance, Epidemiology, and End Results incidence data and conducted a population-based case-control study to examine the role of human papillomavirus (HPV) and oral contraceptive (OC) use in the etiology of adenocarcinoma in situ of the cervix (ACIS). One hundred and fifty women diagnosed with ACIS and 651 randomly selected control women completed in-person interviews. The presence of HPV DNA in archival ACIS specimens was determined by E6 and L1 consensus PCR. Serum samples from case and control subjects were collected at interview, and antibodies to HPV-16 L1 and HPV-18 L1 were detected by virus-like particle capture assays. The overall prevalence of HPV DNA was 86.6%, with 39.0% positive for HPV-16 DNA, 52.4% positive for HPV-18 DNA, and 13.4% positive for more than one HPV type. The age-adjusted relative risk of ACIS associated with HPV-18 seropositivity was 3.3 (95% confidence interval 2.2-4.9). No increased risk was associated with antibodies to HPV-16 L1. Among women born after 1945, the relative risk increased with duration of OC use, with the highest risk for 12 or more years of use (odds ratio, 5.5; 95% confidence interval, 2.1-14.6) relative to nonusers. The detection of HPV DNA in 86.6% of ACIS and the strong association of ACIS with HPV-18 L1 seropositivity underscore the importance of HPV, particularly HPV-18, in the etiology of ACIS. In addition, long-term OC use may contribute to the pathogenesis of these tumors in some women.     

Human papillomavirus type 16 and TP53 mutation in oral cancer: matched analysis of the IARC multicenter study

TP53 mutations were analyzed in 35 human papillomavirus (HPV) type 16 DNA-positive cancers of the oral cavity and oropharynx and in 35 HPV DNA-negative cancers matched by subsite, country, sex, age, and tobacco and alcohol consumption. Wild-type TP53 was found more frequently in cancer specimens that contained HPV16 DNA than in those that did not. All 14 HPV16 DNA-positive cancers in HPV16 E6 antibody-positive patients contained wild-type TP53, compared with 50% of corresponding HPV DNA-negative cancers (matched odds ratio, infinity; 95% confidence interval, 1.4- infinity ). In contrast, for HPV16 DNA-positive cancers in E6-negative patients, wild-type TP53 frequency was similar to that in corresponding HPV DNA-negative cancers (matched odds ratio, 1.0; 95% confidence interval, 0.2-5.4). TP53 inactivation is a major mechanism of HPV-related carcinogenesis in the oral cavity and oropharynx. The role of HPV in cancers also containing TP53 mutations remains to be clarified.     

A prospective analysis of smoking and human papillomavirus infection among men in the HPV in Men Study

At present it is unknown whether the higher prevalence of human papillomavirus (HPV) infection among smokers in men is attributed to a higher probability of acquiring an infection or because of longer infection persistence. Thus, we investigated the role of smoking on the incidence (acquisition) and clearance (persistence) of genital HPV infections among 4,026 men in the HPV in Men (HIM) Study, a multinational prospective study of the natural history of genital HPV infection in men. Genital HPV infections were grouped by any, oncogenic and nononcogenic HPV infections and smoking status was categorized as current, former and never smokers. The incidence of any, oncogenic and nononcogenic HPV infections was significantly higher among current smokers compared to former and never smokers (p < 0.01). In multivariable analyses adjusting for sexual behavior and potential confounders, when compared to never smokers, current smokers exhibited significantly higher probability of acquiring any [hazard ratio (HR) = 1.23; 95% confidence interval (CI) 1.02–1.50] and nononcogenic (HR = 1.21; 95% CI 1.00–1.45) infections and a borderline significant probability for oncogenic infections (HR = 1.18; 95% CI 0.98–1.41). Although the median duration of HPV infection was generally longer among current smokers, we found no statistically significant associations in the multivariable analyses. Overall, these results demonstrated that current smoking exhibited the highest incidence and highest probability of acquiring genital HPV infections.     

Cervical cytokines and clearance of incident human papillomavirus infection: Hawaii HPV cohort study

Mechanisms for the control and resolution of human papillomavirus (HPV) infection of the cervix include the local production of cytokines, which control recruitment and function of cells integral to pathogen control. We established a cohort of women for long‐term follow‐up to examine the mucosal expression of antiviral (IFN‐α2), Type‐1 (IFN‐γ, IL‐12), regulatory (IL‐10), and proinflammatory (IL‐1α, IL‐1β, IL‐6, IL‐8, MIP‐1α, and TNF) cytokines in association with the clearance of incident cervical HPV infection. Interviews and specimens for HPV DNA analysis and cytokine protein measurement were obtained at baseline and at 4‐month intervals. A Cox proportional hazards model was used to study the relationship between clearance of 107 high‐risk and 111 low‐risk incident HPV infections and cytokine levels among 154 women. Positive changes from baseline levels of IL‐10, IL‐12, MIP‐1α, and TNF were associated with significantly longer times to type‐specific HPV clearance. Inverse trends in the hazard ratios associated with clearance of high‐risk HPV infections were monotonic and significant for IL‐12 (p_trend = 0.02) and TNF (p_trend = 0.02); the likelihood of high‐risk HPV clearance was reduced by 65% and 67%, respectively, among women in the highest as compared with the lowest quartile of change from baseline. Our results suggest that in women with a nontransient cervical HPV infection, proinflammatory, Type‐1, and regulatory cytokines are elevated, underscoring the long‐term commitment of local immune mediators to viral eradication.     

Reproductive and sex hormonal factors and oesophageal and gastric junction adenocarcinoma: A pooled analysis

BackgroundThe rapidly rising incidence and the striking male predominance are as yet unexplained features of oesophageal and gastric junction adenocarcinoma. Few and underpowered studies have examined the impact of female reproductive factors on risk of these adenocarcinomas in women. We therefore pooled data on women from four population-based case-control studies to examine the association of female reproductive and sex hormonal factors with oesophageal and gastric junction adenocarcinoma.MethodsData on women from case-control studies conducted in Ireland, the United Kingdom (UK), Australia and United States of America (USA) were pooled. Multivariable logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for a range of reproductive factors, adjusted for age, study and major risk factors for oesophageal and gastric junction adenocarcinoma.ResultsWe included 218 cases and 862 controls. Among parous women, a reduced risk of oesophageal and gastric junction adenocarcinoma was found after breastfeeding (OR = 0.58, 95% CI = 0.37–0.92) and the risk decreased with increased duration of breastfeeding (>12 months OR = 0.42, 95% CI = 0.23–0.77). The endogenous reproductive factors such as parity, menstruation, history of pregnancy and the exogenous factors such as use of oral contraceptives and of hormone replacement therapy were not statistically significantly associated with oesophageal and gastric junction adenocarcinoma.ConclusionOur findings suggest that breastfeeding is associated with a decreased risk of oesophageal and gastric junction adenocarcinoma. The potential mechanism of this association warrants further investigation.     

The human papillomavirus infection in men study: human papillomavirus prevalence and type distribution among men residing in Brazil, Mexico, and the United States

Male sexual behavior influences the rates of cervical dysplasia and invasive cervical cancer, as well as male human papillomavirus (HPV) infection and disease. Unfortunately, little is known regarding male HPV type distribution by age and across countries. In samples combined from the coronal sulcus, glans penis, shaft, and scrotum of 1,160 men from Brazil, Mexico, and the United States, overall HPV prevalence was 65.2%, with 12.0% oncogenic types only, 20.7% nononcogenic types only, 17.8% both oncogenic and nononcogenic, and 14.7% unclassified infections. Multiple HPV types were detected in 25.7% of study participants. HPV prevalence was higher in Brazil (72.3%) than in the United States (61.3%) and Mexico (61.9%). HPV16 (6.5%), HPV51 (5.3%), and HPV59 (5.3%) were the most commonly detected oncogenic infections, and HPV84 (7.7%), HPV62 (7.3%), and HPV6 (6.6%) were the most commonly detected nononcogenic infections. Overall HPV prevalence was not associated with age. However, significant associations with age were observed when specific categories of HPV, nononcogenic, and unclassified HPV infections were considered. Studies of HPV type distribution among a broad age range of men from multiple countries is needed to fill the information gap internationally with respect to our knowledge of HPV infection in men.