Salvatore Vaccarella

Sexual behaviours and the risk of head and neck cancers: a pooled analysis in the International Head and Neck Cancer Epidemiology (INHANCE) consortium

BACKGROUND Sexual contact may be the means by which head and neck cancer patients are exposed to human papillomavirus (HPV). METHODS We undertook a pooled analysis of four population-based and four hospital-based case-control studies from the International Head and Neck Cancer Epidemiology (INHANCE) consortium, with participants from Argentina, Australia, Brazil, Canada, Cuba, India, Italy, Spain, Poland, Puerto Rico, Russia and the USA. The study included 5642 head and neck cancer cases and 6069 controls. We calculated odds ratios (ORs) of associations between cancer and specific sexual behaviours, including practice of oral sex, number of lifetime sexual partners and oral sex partners, age at sexual debut, a history of same-sex contact and a history of oral-anal contact. Findings were stratified by sex and disease subsite. RESULTS Cancer of the oropharynx was associated with having a history of six or more lifetime sexual partners [OR = 1.25, 95% confidence interval (CI) 1.01, 1.54] and four or more lifetime oral sex partners (OR = 2.25, 95% CI 1.42, 3.58). Cancer of the tonsil was associated with four or more lifetime oral sex partners (OR = 3.36, 95 % CI 1.32, 8.53), and, among men, with ever having oral sex (OR = 1.59, 95% CI 1.09, 2.33) and with an earlier age at sexual debut (OR = 2.36, 95% CI 1.37, 5.05). Cancer of the base of the tongue was associated with ever having oral sex among women (OR = 4.32, 95% CI 1.06, 17.6), having two sexual partners in comparison with only one (OR = 2.02, 95% CI 1.19, 3.46) and, among men, with a history of same-sex sexual contact (OR = 8.89, 95% CI 2.14, 36.8). CONCLUSIONS Sexual behaviours are associated with cancer risk at the head and neck cancer subsites that have previously been associated with HPV infection.

Oral cancer in southern India: The influence of smoking, drinking, paan‐chewing and oral hygiene

Between 1996 and 1999 we carried out a case‐control study in 3 areas in Southern India (Bangalore, Madras and Trivandrum) including 591 incident cases of cancer of the oral cavity (282 women) and 582 hospital controls (290 women), frequency‐matched with cases by age and gender. Odds ratios (ORs) and 95% confidence intervals (CIs) were obtained from unconditional multiple logistic regressions and adjusted for age, gender, center, education, chewing habit and (men only) smoking and drinking habits. Low educational attainment, occupation as a farmer or manual worker and various indicators of poor oral hygiene were associated with significantly increased risk. An OR of 2.5 (95% CI 1.4–4.4) was found in men for smoking ≥ 20 bidi or equivalents versus 0/day. The OR for alcohol drinking was 2.2 (95% CI 1.4–3.3). The OR for paan chewing was more elevated among women (OR 42; 95% CI 24–76) than among men (OR 5.1; 95% CI 3.4–7.8). A similar OR was found among chewers of paan with (OR 6.1 in men and 46 in women) and without tobacco (OR 4.2 in men and 16.4 in women). Among men, 35% of oral cancer is attributable to the combination of smoking and alcohol drinking and 49% to pan‐tobacco chewing. Among women, chewing and poor oral hygiene explained 95% of oral cancer.

Dietary glycemic index and glycemic load, and breast cancer risk: A case-control study

BACKGROUND Certain types of carbohydrates increase glucose and insulin levels to a greater extent than others. In turn, insulin may raise levels of insulin-like growth factors, which may influence breast cancer risk. We analyzed the effect of type and amount of carbohydrates on breast cancer risk, using the glycemic index and the glycemic load measures in a large case-control study conducted in Italy. PATIENTS AND METHODS Cases were 2,569 women with incident, histologically-confirmed breast cancer interviewed between 1991 and 1994. Controls were 2588 women admitted to the same hospital network for a variety of acute, non-neoplastic conditions. Average daily glycemic index and glycemic load were calculated from a validated 78-item food frequency questionnaire. RESULTS Direct associations with breast cancer risk emerged for glycemic index (odds ratio, OR for highest vs. lowest quintile = 1.4; P for trend <0.01) and glycemic load (OR = 1.3; P < 0.01). High glycemic index foods, such as white bread, increased the risk of breast cancer (OR = 1.3) while the intake of pasta, a medium glycemic index food, seemed to have no influence (OR = 1.0). Findings were consistent across different strata of menopausal status, alcohol intake, and physical activity level. CONCLUSIONS This study supports the hypothesis of moderate, direct associations between glycemic index or glycemic load and breast cancer risk and, consequently, a possible role of hyperinsulinemia/insulin resistance in breast cancer development.

Prevalence and Determinants of Genital Infection with Papillomavirus, in Female and Male University Students in Busan, South Korea

BACKGROUND Little is known about the prevalence of human papillomavirus (HPV) infection in young adults in Asia. METHODS We invited female and male students in Busan, South Korea, to participate in a survey that included, for females, self-collection of vaginal cells and, for males, physician-performed collection of exfoliated genital cells. The prevalences of 25 HPV types were evaluated, by a polymerase chain reaction-based assay, in 672 female students (median age, 19 years) and in 381 male students (median age, 22 years). RESULTS HPV DNA was detected more frequently in female students (15.2%) than in male students (8.7%); in both sexes, high-risk HPV types were predominant. Among sexually active students, HPV prevalence was 38.8% in females and 10.6% in males. In female students, currently smoking cigarettes and having multiple lifetime sex partners were the strongest risk factors for HPV infection; in male students, associations between HPV prevalence and sexual habits were similar to those in female students but never attained statistical significance. CONCLUSIONS Young women in South Korea start having penetrative sexual intercourse relatively late (median age, 18 years), but, once they begin, HPV prevalence quickly rises to levels comparable with those found in university students in the United States and in northern Europe. The high rate of participation in our study suggests that trials of new vaccines against HPV may be feasible among university students in South Korea.

Combined effect of tobacco and alcohol on laryngeal cancer risk: a case-control study

Objective: To provide information on the effects of alcohol and tobacco on laryngeal cancer and its subsites. Methods: This was a case–control study conducted between 1992 and 2000 in northern Italy and Switzerland. A total of 527 cases of incident squamous-cell carcinoma of the larynx and 1297 hospital controls frequency-matched with cases on age, sex, and area of residence were included. Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were estimated using multiple logistic regression. Results: In comparison with never smokers, ORs were 19.8 for current smokers and 7.0 for ex-smokers. The risk increased in relation to the number of cigarettes (OR = 42.9 for ≥25 cigarettes/day) and for duration of smoking (OR = 37.2 for ≥40 years). For alcohol, the risk increased in relation to number of drinks (OR = 5.9 for ≥56 drinks per week). Combined alcohol and tobacco consumption showed a multiplicative (OR = 177) rather than an additive risk. For current smokers and current drinkers the risk was higher for supraglottis (ORs 54.9 and 2.6, respectively) than for glottis (ORs 7.4 and 1.8) and others subsites (ORs 10.9 and 1.9). Conclusions: Our study shows that both cigarette smoking and alcohol drinking are independent risk factors for laryngeal cancer. Heavy consumption of alcohol and cigarettes determined a multiplicative risk increase, possibly suggesting biological synergy.

Worldwide Thyroid-Cancer Epidemic? The Increasing Impact of Overdiagnosis

Dramatic increases have been seen over recent decades in the reported incidence of thyroid cancer, but owing to new modes of screening, hundreds of thousands of cases may be overdiagnoses — diagnosis of tumors that would not, if left alone, result in symptoms or death.

Human papillomavirus infection among women in South and North Vietnam.

The incidence rate of invasive cervical carcinoma (ICC) is 4‐fold higher in Ho Chi Minh City, in the South of Vietnam, than in Hanoi, in the North. Thus, we explored the prevalence of and the risk factors for human papillomavirus (HPV) infection in these 2 areas. A population‐based random sample of married women aged 15–69 years were interviewed and had a gynaecological examination in the urban district of Ho Chi Minh City and in a peri‐urban district in Hanoi. HPV DNA detection was performed using a GP5+/6+ primer‐mediated PCR enzyme immunoassay. A total of 922 women from Ho Chi Minh and 994 from Hanoi, for whom a Pap smear and HPV‐status were available, were evaluated. HPV DNA was detected among 10.9% of women in Ho Chi Minh City and 2.0% in Hanoi (age standardized prevalence, world standard population: 10.6% and 2.3%, respectively). In the 2 areas combined, 30 different HPV types were found, the most common being HPV 16 (in 14 single and 18 multiple infections), followed by HPV 58, 18 and 56. A peak of HPV DNA detection in women younger than age 25 was found in Ho Chi Minh City (22.3%) but not in Hanoi. Major risk factors for HPV DNA detection were indicators of sexual habits, most notably the presence of HSV‐2 antibodies, nulliparity and the current use of oral contraceptives. Women in Hanoi showed the lowest HPV prevalence ever reported so far, suggesting that HPV has not spread widely in this population. As expected, HPV prevalence in a population seemed to be closely correlated with ICC incidence rates.

Worldwide trends in cervical cancer incidence: Impact of screening against changes in disease risk factors

BACKGROUND Cervical cancer trends in a given country mainly depend on the existence of effective screening programmes and time changes in disease risk factors, notably exposure to human papillomavirus (HPV). Screening primarily influences variations by period of diagnosis, whereas changes in risk factors chiefly manifest themselves as variations in risk across successive birth cohorts of women. METHODS We assessed trends in cervical cancer across 38 countries in five continents, age group 30-74 years, using age-standardised incidence rates (ASRs) and age-period-cohort (APC) models. Non-identifiability in APC models was circumvented by making assumptions based on a consistent relationship between age and cervical cancer incidence (i.e. approximately constant rates after age 45 years). FINDINGS ASRs decreased in several countries, except in most of Eastern European populations, Thailand as well as Uganda, although the direction and magnitude of period and birth cohort effects varied substantially. Strong downward trends in cervical cancer risk by period were found in the highest-income countries, whereas no clear changes by period were found in lower-resourced settings. Successive generations of women born after 1940 or 1950 exhibited either an increase in risk of cervical cancer (in most European countries, Japan, China), no substantial changes (North America and Australia) or a decrease (Ecuador and India). INTERPRETATION In countries where effective screening has been in place for a long time the consequences of underlying increases in cohort-specific risk were largely avoided. In the absence of screening, cohort-led increases or, stable, cervical cancer ASRs were observed. Our study underscores the importance of strengthening screening efforts and augmenting existing cancer control efforts with HPV vaccination, notably in those countries where unfavourable cohort effects are continuing or emerging. FUNDING Bill and Melinda Gates Foundation (BMGF).

Smoking and human papillomavirus infection: pooled analysis of the International Agency for Research on Cancer HPV Prevalence Surveys

BACKGROUND Smoking increases the risk of squamous-cell carcinoma of the cervix, but it is not clear whether smoking increases the risk of acquisition or persistence of human papillomavirus (HPV) infection. METHODS Information on smoking was collected from 10 areas in four continents among population-based, age-stratified random samples of women aged 15 years or older. HPV testing was performed using PCR-based enzyme immunoassay. Unconditional logistic regression was used to estimate odds ratios (OR) and corresponding 95% confidence intervals (CI) of being HPV-positive by smoking habits, adjusted for age and lifetime number of sexual partners. RESULTS Ten thousand five hundred and seventy-seven women (mean age 41.4 years) were included. Among current smokers, the risk of being HPV-positive increased with smoking intensity, after allowing for lifetime number of sexual partners: ORs for <5, 5-14 and >/=15 cigarettes per day were 1.21 (95% CI 0.95-1.54), 1.39 (95% CI 1.04-1.87) and 2.01 (95% CI 1.32-3.08), respectively, as compared with never-smokers. The risk among former smokers (OR = 0.95, 95% CI 0.73-1.23) was similar to that among never-smokers. Analyses stratified by lifetime number of sexual partners showed a significant trend in risk only for women with one lifetime sexual partner. CONCLUSIONS Our study suggests that current, though not former, smoking is associated with an increased prevalence of HPV, after allowance for sexual covariates. Among current smokers, HPV prevalence increased with smoking intensity, but a clear dose-response relationship was exclusively seen among women who declared one lifetime sexual partner.

Prevalence of human papillomavirus infection in women in Busan, South Korea.

To investigate the prevalence of and the risk factors for human papillomavirus (HPV) infection in South Korea, we interviewed and examined a randomly selected sample of 863 sexually active women (age range = 20–74 years, median 44) and 103 self‐reported virgins from Busan. The presence of DNA of 34 different HPV types in cervical exfoliated cells was tested among sexually active women by means of a PCR‐based assay. IgG antibodies against L1 virus‐like particles (anti‐VLPs) of HPV types 16, 18, 31, 33 and 58 were also evaluated by means of ELISA. The overall prevalence of HPV DNA was 10.4% (95% confidence interval, CI: 8.5–12.7%). The most often found HPV DNA types were HPV 70, HPV 16 and HPV 33; 19.8% (95% CI: 17.2–22.0) of sexually active women had antibodies against one or more HPV types. The most common anti‐VLPs were against HPV 18, 31 and 16. Prevalences standardized by age on the basis of the world standard population were 13.0% for HPV DNA and 17.1% for anti‐VLPs. The concordance between the 2 HPV markers at an individual level was modest, but the risk factors for detection of HPV DNA and anti‐VLPs were similar: number of lifetime sexual partners (odds ratio, OR for ≥ 4 vs. 1 = 3.5 and 5.4, respectively), seropositivity for herpes simplex virus‐2 antibodies (OR = 2.6 and 2.5, respectively) and being single or divorced. HPV DNA, but not anti‐VLPs, were elevated among women whose husbands were thought by their wives to have extra‐marital affairs and those who had undergone vasectomy. Among 103 virgins, 4.9% had anti‐VLPs (1/73 among those aged 24 years or less).