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.     

Reproductive factors, oral contraceptive use, and human papillomavirus infection: pooled analysis of the IARC HPV prevalence surveys.

High parity, early age at first full-term pregnancy (FTP), and long-term oral contraceptive (OC) use increase cervical cancer risk, but it is unclear whether these variables are also associated with increased risk of acquisition and persistence of human papillomavirus (HPV) infection, the main cause of cervical cancer. Information on reproductive and menstrual characteristics and OC use were collected from 14 areas worldwide, among population-based, age-stratified random samples of women aged 15 years or older. HPV testing was done using PCR-based enzyme immunoassay. Unconditional logistic regression was used to estimate the odds ratios (OR) of being HPV-positive according to reproductive and menstrual factors and corresponding 95% confidence intervals (CI). When more than two groups were compared, floating CIs (FCI) were estimated. A total of 15,145 women (mean age, 40.9 years) were analyzed. Women with >or=5 FTPs (OR, 0.90; 95% FCI, 0.76-1.06) showed a similar risk of being HPV-positive compared with women with only one FTP (OR, 1.00; 95% FCI, 0.86-1.16). However, nulliparous women showed an OR of 1.40 (95% CI, 1.16-1.69) compared with parous women. Early age at first FTP was not significantly related to HPV positivity. HPV positivity was similar for women who reported >or=10 years of use of OCs (OR, 1.16; 95% FCI, 0.85-1.58) and never users of OCs (OR, 1.00; 95% FCI, 0.90-1.12). Our study suggests, therefore, that high parity, early age at first FTP, and long-term OC use are not associated with HPV prevalence, but rather these factors might be involved in the transition from HPV infection to neoplastic cervical lesions.     

Epigenetics and cancer, 2nd IARC meeting,Lyon, France, 6 and 7 December 2007

It is becoming widely accepted that epigenetic alterations are universally present in human malignancies and that cancer is as much a disease of abnormal epigenetics as it is a genetic disease. The potential utility of epigenetics and epigenomics in cancer research and cancer control is highlighted by the fact that many funding agencies put cancer epigenetics on the priority list. The goal of this meeting, held at the offices of the International Agency for Research on Cancer in Lyon, France, 6 and 7 December 2007, was to discuss recent conceptual and technological advances in cancer epigenetics and epigenomics, the future research needs in the field, and their implications for early detection, risk assessment and prevention of cancer.While epigenetics has been historically linked to phenomena that do not follow normal genetic principles of heritability, recent mechanistic advances have begun to change our understanding of complex diseases including cancer, traditionally viewed as genetic in origin. It is now known that epigenetic mechanisms play critical roles in regulation of many cellular functions and their deregulation may disrupt the control of fundamental processes leading to tumour formation. A flurry of screening and functional studies revealed that most key processes found in cancer cells, such as silencing of tumour suppressor genes, activation of oncogenes, aberrant cell cycle processes, defects in DNA repair, and deregulation of cell death, can be triggered by epigenetic deregulation. Two important features that distinguish epigenetic changes from genetic alterations are the gradual appearance and reversibility of epigenetic events. These features make epigenetic alterations an attractive target for therapeutic intervention and the development of preventive strategies. For example, aberrant patterns of DNA methylation and histone acetylation and methylation can be targeted by drugs aiming to re‐activate epigenetically silenced genes. Until now, most studies on epigenetic changes in cancer were generally focused on specific genes. However, this meeting also stressed the need to take advantage of recent progress in epigenomics and emergence of powerful technologies for detection of epigenetic changes in high throughput and genome‐wide settings. This may further advance our capacity to evaluate the contribution of epigenetic changes induced by environmental epimutagens to human cancer. This information may prove critical for the design of efficient strategies for early diagnosis, therapy, and prevention of cancer.