Is an oropharyngeal HPV infection more frequently detectable in women with a genital HPV infection?

PURPOSE: If not eliminated by the immune system and persisting over years, oropharyngeal high-risk HPV infection can lead to cancer development in the oropharynx. HPV infection is very commonly found in the genital region and can serve as an HPV reservoir. In this study, we investigate whether women with a genital HPV infection are at a higher risk of harboring an undetected oropharyngeal HPV infection via genital-oropharyngeal transmission. METHODS: Women presenting for routine gynecological checkups were included in this study. All participants received an HPV brush test from the genital region as well as from the oropharynx. Additionally, probable risk factors for an HPV infection were assessed in a structured questionnaire. RESULTS: 142 women were included in this study. The rate of oropharyngeal HPV infection was low with 2/142 (1,4%) women positive for a low-risk HPV genotype. In the genital brush test, 54/142 (38%) women were tested HPV positive of which 41/142 (29%) were positive for a high-risk HPV genotype. CONCLUSIONS: The rate of an oropharyngeal HPV detection in our population was low with 2/142 women harboring a low-risk HPV infection.

Factors affecting children's HPV vaccination in Austria: Evidence from a parent survey.

Human papillomavirus (HPV) is a sexually transmitted infection that causes cervical cancer, head and neck cancer, other urogenital cancers, and genital warts. In Austria, where HPV vaccination is free for children, the vaccination rate nevertheless remains insufficient for herd immunity against HPV. Using a cross-sectional survey of parents (N = 334) in the state of Tyrol, Austria, we examined parents' reasons for rejecting children's HPV vaccination and key predictors of vaccination intention for their children, including knowledge about HPV, attitude toward vaccination, sources of information about the HPV vaccine, socioeconomic factors, and HPV vaccination intention. Data analyzed using descriptive statistics and logistic regression modeling revealed an overall 81.9% acceptance rate of HPV vaccination. The most common reasons for vaccine hesitancy were a fear of side effects, a perceived lack of information, and the perception that children are too young to be vaccinated. A high level of knowledge about HPV was significantly associated with vaccine acceptance for female but not male children. Negative attitude toward vaccination was significantly related to lower vaccine acceptance, and parents who reported informing themselves about HPV vaccination from online sources were less likely to accept vaccination. Such results call for more educational measures to reduce misinformation about HPV vaccination and thereby reduce the fear of its side effects and promote early vaccination. More information is also needed to improve parents' attitude toward and their knowledge about vaccination, the dissemination of which should focus on the benefits of vaccines for children of both sexes.

Regimen of Coronavirus Disease 2019 Vaccination Influences Extent and Kinetics of Antibody Avidity.

We investigated antibody titers and avidity after heterologous versus homologous coronavirus disease 2019 vaccination over 6 months after the second dose. We found a significantly higher avidity in regimens including at least 1 dose of the adenoviral vector vaccine ChAdOx1-S compared with 2 doses of the mRNA vaccine BNT162b2.

14-year-old Schoolchildren can Consent to Get Vaccinated in Tyrol, Austria: What do They know about Diseases and Vaccinations?

In Austria, consent to receiving vaccines is regulated at the federal state level and in Tyrol, children aged 14 years are allowed to consent to receiving vaccination. In August 2017, we investigated determinants associated with vaccine hesitancy, having been vaccinated against measles and human papillomavirus (HPV) and the intention to vaccinate among schoolchildren born in 2002 and 2003. Those who consider measles and HPV a severe disease had a significantly higher intention to be vaccinated (prevalence ratio (PR) of 3.5 (95% CI 1.97-6.32) for measles and a PR of 3.2 (95% CI 1.62-6.35) for HPV). One-third of the participants (32.4%; 95% CI 27.8-37.4) were not aware that they are allowed to consent to receiving vaccines. The most common trusted source reported by respondents (n = 311) was the medical doctor (80.7%; 95% CI 75.7-84.7). The main finding related to the aim of the study was that the proportion of objectors is below 4% and therefore it should still be possible to reach measles elimination for which a 95% uptake is necessary. Although the proportion of objectors is not higher compared to adults, we recommend to intensify health education to increase health literacy.

HPV-Induced Oropharyngeal Cancer and the Role of the E7 Oncoprotein Detection via Brush Test.

Background: High risk human papillomavirus (hr-HPV)-associated oropharyngeal cancers (OPCs) are characterized by significantly better therapy responses. In order to implement a de-escalated treatment strategy for this tumor entity, it is highly crucial to accurately distinguish HPV-associated OPCs from non-HPV-associated ones. Methods: In this prospective study, 56 patients with histologically confirmed OPC were evaluated. A commercially available sandwich ELISA test system was used for the detection of hr-HPV E7 oncoprotein targeting the genotypes 16, 18 and 45. Results were presented as optical density. Positivity for HPV DNA and p16 immunohistochemistry (IHC) was taken as the reference method. Results: E7 positivity was significantly associated with the reference method (p = 0.048). The sensitivity, specificity, positive predictive value and negative predictive value for the E7 oncoptotein was 60.9% (95% CI 38.5 to 80.3%), 66.7% (95% CI 46% to 83.5%), 64.2% (95% CI 49.4 to 77.4%) and 63.01% (95% CI 48.9-75.2%), respectively, for the cutoff provided by the manufacturer. Conclusions: We found a significant association between E7 oncoprotein detection and the currently used combination. We believe that the use of the ELISA based E7 antigen test could be a valuable addition in cases of ambiguous findings and may be used in combination with other techniques to distinguish between HPV-driven and non-HPV-driven OPCs. However, the low sensitivity of the assay coupled with the small sample size in our study may represent a limitation. We recommend that future larger studies elucidate the diagnostic value of the E7 brush test.

The Role of HPV and Non-HPV Sexually Transmitted Infections in Patients with Oropharyngeal Carcinoma: A Case Control Study.

Background: Certain high-risk (hr) types of human papillomavirus (HPV) can cause cervical cancer in women and penile cancer in men. Hr-HPV can also cause cancers of the oropharynx and anus in both sexes. In the anal and cervical region, a contribution of co-infections with Ureaplasma spp. on the persistence of the hr-HPV infection by a profound inflammatory state is suggested. Here, we investigated if non-HPV sexually transmitted infections are associated with oropharyngeal carcinoma (OPC). Materials and Methods: In this case-control study, a brush test directly from the tumor surface of OPC patients (study group) and from the oropharynx of healthy volunteers (control group), both groups matching in age and sex, was performed. HPV subtypes were detected using a commercially available test kit. For non-HPV sexually transmitted infections (Ureaplasma spp., Chlamydia trachomatis, Mycoplasma hominis, and Mycoplasma genitalium), a multiplex nucleic acid amplification approach was performed. Results: In the study group, 96 patients (23 female/73 male), with histologically confirmed OPC and in the control group 112 patients (19 female/93 male), were included. Oropharyngeal hr-HPV-positivity was detected in 68% (65/96 patients) of the study group and 1.8% (2/112 patients) of the control group (p < 0.001). In three patients in the study group, Ureaplasma spp. was detected, whereas no patient was Ureaplasma spp. positive in the control group (p = 0.097). Chlamydia trachomatis, Mycoplasma hominis, and Mycoplasma genitalium were negative in both groups. Conclusion: Based on the current study, the prevalence of oropharyngeal Ureaplasma spp. among patients with OPC is low and does not support a role in oropharyngeal cancer. However, the detection of the pathogen only among OPC patients but not in the healthy individuals might indicate a potential role and needs further elucidation.

Post-Treatment HPV Surface Brushings and Risk of Relapse in Oropharyngeal Carcinoma.

Human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC) is a distinct subtype of head and neck cancer. Here, we investigated how frequently brushing remained high-risk (hr)-HPV positive after treatment and whether patients with positive post-treatment brushings have a higher recurrence rate. Following the end of treatment of patients with initially hr-HPV positive OPSCC, surface brushings from the previous tumor site were performed and tested for hr-HPV DNA. Of 62 patients with initially hr-HPV DNA-positive OPSCC, seven patients remained hr-HPV-DNA positive at post-treatment follow-up. Of the seven hr-HPV-positive patients at follow-up, five had a tumor relapse or tumor progression, of whom three died. The majority of patients (55/62) was HPV-negative following treatment. All HPV-negative patients remained free of disease (p = 0.0007). In this study, all patients with recurrence were hr-HPV-positive with the same genotype as that before treatment. In patients who were hr-HPV negative after treatment, no recurrence was observed.

Reducing overtreatment associated with overdiagnosis in cervical cancer screening-A model-based benefit-harm analysis for Austria.

A general concern exists that cervical cancer screening using human papillomavirus (HPV) testing may lead to considerable overtreatment. We evaluated the trade-off between benefits and overtreatment among different screening strategies differing by primary tests (cytology, p16/Ki-67, HPV alone or in combinations), interval, age and diagnostic follow-up algorithms. A Markov state-transition model calibrated to the Austrian epidemiological context was used to predict cervical cancer cases, deaths, overtreatments and incremental harm-benefit ratios (IHBR) for each strategy. When considering the same screening interval, HPV-based screening strategies were more effective compared to cytology or p16/Ki-67 testing (e.g., relative reduction in cervical cancer with biennial screening: 67.7% for HPV + Pap cotesting, 57.3% for cytology and 65.5% for p16/Ki-67), but were associated with increased overtreatment (e.g., 19.8% more conizations with biennial HPV + Papcotesting vs. biennial cytology). The IHBRs measured in unnecessary conizations per additional prevented cancer-related death were 31 (quinquennial Pap + p16/Ki-67-triage), 49 (triennial Pap + p16/Ki-67-triage), 58 (triennial HPV + Pap cotesting), 66 (biennial HPV + Pap cotesting), 189 (annual Pap + p16/Ki-67-triage) and 401 (annual p16/Ki-67 testing alone). The IHBRs increased significantly with increasing screening adherence rates and slightly with lower age at screening initiation, with a reduction in HPV incidence or with lower Pap-test sensitivity. Depending on the accepted IHBR threshold, biennial or triennial HPV-based screening in women as of age 30 and biennial cytology in younger women may be considered in opportunistic screening settings with low or moderate adherence such as in Austria. In organized settings with high screening adherence and in postvaccination settings with lower HPV prevalence, the interval may be prolonged.

Anal Ureaplasma spp. positivity among HIV positive men who have sex with men may be associated with high-risk-type HPV infections.

OBJECTIVE: HIV positive individuals, particularly men having sex with men (MSM), are at increased risk of sexually transmitted infections (STIs) at genital and extra-genital sites. Data on anorectal Ureaplasma infections are lacking. The aim of our study was to characterize anal Ureaplasma positivity among a cohort of HIV positive MSM and evaluate possible association with papillomavirus infection at the same site. METHODS: Anal swab samples, collected as part of routine screening for Chlamydia trachomatis and Neisseria gonorrhea, were additionally tested for HPV genotypes as well as for Ureaplasma and Mycoplasma using nucleic acid amplification method. RESULTS: Out of a total of 222 study participants, 195 (89%, 95% CI (84.9-93.2)) were positive for HPV, approximately three quarter being high-risk genotypes. Forty three individuals (19.4%, 95% CI (14.4-24.3)) harbored Ureaplasma spp. Infection with high-risk HPV types was significantly associated with co-presence of Ureaplasma with an odds ratio (95% confidence-interval) of 2.59 (1.03-6.54), P = 0.04. CONCLUSION: Besides a high predominance of HPV infection, asymptomatic HIV positive MSM had a high prevalence of anal Ureaplasma positivity. Concomitant infections with high-risk HPV genotypes were common and statistically significant. The role of this co-existence as a potential risk factor for anal carcinogenesis needs further elucidation.

Epidemiology and clinical profile of pathogens responsible for the hospitalization of children in Sousse area, Tunisia.

This study aimed to identify a broad spectrum of respiratory pathogens from hospitalized and not-preselected children with acute respiratory tract infections in the Farhat Hached University-hospital of Sousse, Tunisia. Between September 2013 and December 2014, samples from 372 children aged between 1 month and 5 years were collected, and tested using multiplex real-time RT-PCR by a commercial assay for 21 respiratory pathogens. In addition, samples were screened for the presence of Streptococcus pneumoniae 16S rDNA using real-time PCR. The viral distribution and its association with clinical symptoms were statistically analyzed. Viral pathogens were detected in 342 (91.93%) of the samples of which 28.76% were single positive and 63.17% had multiple infections. The most frequent detected viruses were rhinovirus (55.64%), respiratory syncytial virus A/B (33.06%), adenovirus (25.00%), coronavirus NL63, HKU1, OC43, and 229E (21.50%), and metapneumovirus A/B (16.12%). Children in the youngest age group (1-3 months) exhibited the highest frequencies of infection. Related to their frequency of detection, RSV A/B was the most associated pathogen with patient's demographic situation and clinical manifestations (p<0.05). Parainfluenza virus 1-4 and parechovirus were found to increase the risk of death (p<0.05). Adenovirus was statistically associated to the manifestation of gastroenteritis (p = 0.004). Rhinovirus infection increases the duration of oxygen support (p = 0.042). Coronavirus group was statistically associated with the manifestation of bronchiolitis (p = 0.009) and laryngitis (p = 0.017). Streptococcus pneumoniae DNA was detected in 143 (38.44%) of tested samples. However, only 53 samples had a concentration of C-reactive protein from equal to higher than 20 milligrams per liter, and 6 of them were single positive for Streptocuccus pneumoniae. This study confirms the high incidence of respiratory viruses in children hospitalized for acute respiratory tract infections in the Sousse area, Tunisia.

Sensitivity of tumor surface brushings to detect human papilloma virus DNA in head and neck cancer.

OBJECTIVE: Human papilloma virus (HPV) induced head and neck squamous cell carcinoma (HNSCC) represents a distinct tumor subset. We questioned how accurately a brushing from the tumor surface detects HPV in patients with HNSCC. MATERIALS AND METHODS: Brushings from the tumor surface were compared with HPV DNA isolation from formalin-fixed and paraffin-embedded (FFPE) tumor biopsies, which served as the reference standard. In both matrices, HPV DNA was detected using a commercially available test kit. In addition, p16 was assessed in tumor biopsies by immunohistochemistry (IHC). The tumors were considered p16 positive if 70% or more of cancer cells expressed p16. RESULTS: 93 patients with HNSCC were included. Sensitivity and specificity of the brush test were 83% (95%CI: 67-92%) and 85% (95%CI: 72-93%). Results of p16 IHC were concordant with FFPE samples DNA determinations in 73/93 patients. In 53 patients (57%) the tumor was located in the oropharynx and in 40 patients (43%) the tumor was located in the non-oropharynx region. Sensitivity and specificity of the brush test in patients with oropharyngeal cancer was higher with 86% (95%CI: 70-95%) and 89% (95%CI: 65-99%). CONCLUSION: Superficial brushes from the tumor surface may be used to identify HPV positive HNSCC.

Correlation between anti-JC-virus and anti-cytomegalovirus, -Epstein-Barr virus and -measles/-rubella/-varicella-zoster-virus antibodies.

Anti-JCV antibody status is used for PML-risk-stratification in MS patients before and during Natalizumab therapy. JCV antibodies can be detected in around 60% of MS patients, however, only a small proportion actually develop PML. As anti-viral antibodies tend to occur unspecifically, the aim of this study was to correlate JCV antibody status and index with other common anti-viral antibodies. A total of 123 samples of MS-patients were tested for anti-JCV antibodies by JCV-Stratify-ELISA at Unilabs, Denmark. The same samples were analyzed for measles, rubella, varicella zoster, EBV, and CMV IgG and IgM antibodies by ELISA, or chemiluminescence-microparticle immunoassay. For all antibody-titers correlations were calculated and group comparisons of JCV-positive and -negative patients were performed. Fifty-three patients (43.1%) were JCV negative and 70 (56.9%) positive. CMV-IgM antibodies were detected in six patients. Otherwise no IgM antibodies were detected. IgG antibodies against measles, rubella, varicella zoster, and EBV were detected in ≥97% of patients and 47 samples (38.2%) tested positive for CMV-IgG. There was no significant correlation between any of the antibody titers including JCV index, however, a significantly higher prevalence (P = 0.003) of CMV-IgG in JCV positive compared to JCV negative patients, whereas no difference was detected for measles, rubella, varicella zoster, and EBV IgG. In conclusion, the JCV antibody response in MS patients seems to be largely independent of any other anti-viral immunity. The only coincidence was found with CMV IgG antibodies which might point towards some immunological cross-reactivity in anti-viral immune response or other mechanisms leading to combined viral infections such as shared transmission. J. Med. Virol. 89:3-9, 2017. © 2016 Wiley Periodicals, Inc.

Pre-vaccine era cervical human papillomavirus infection among screening population of women in west Austria.

BACKGROUND: In order to evaluate the newly implemented gender-neutral HPV vaccination program, knowledge on the pre-vaccine prevalence of HPV infection is of paramount importance. Data on HPV infection among the women with no known previous cytological abnormalities are inexistent in Austria. This study presents data on the prevalence and distribution of HPV genotypes among women with no known cytological abnormalities in west Austria. METHODS: Women between 18 and 65 years of age attending annual cervical cancer screening examinations were included in the study. Data on socio-demographic and reproductive factors were collected using structured questionnaires. Corresponding cervical swab samples were tested for the presence of HPV DNA and were genotyped. Questionnaire data and HPV status were linked with the corresponding cytological findings. RESULTS: A total of 542 women were included in the study. The mean age of the study participants was 35.9 (SD = 11.5). The prevalence of HPV infection was 20.5 %. HPV 16 (6.5 %), HPV 33 (3.3 %) and HPV 31 (3.0 %) were the dominant genotypes detected. Multivariate analysis showed that women younger than 30 years of age, smokers, women with a higher number of lifetime sexual partners and those living in the eastern districts of the study region were at significantly higher risk of HPV infection. CONCLUSIONS: With this study we present the first data on the prevalence of cervical HPV genotypes among a screening population in Austria. The results not only fill the missing information on HPV infection in this group of women in the country, they also provide baseline data for a future evaluation of the impact of the Austrian gender-neutral HPV immunization program. Moreover, our finding of higher HPV prevalence in the eastern compared to the western district of the study region may - at least partly - explain the east-west gradient in the standardized incidence rate of cervical cancer in the region.

Factors affecting HPV vaccine acceptance in west Austria: Do we need to revise the current immunization scheme?

BACKGROUND: Austria introduced a school-based gender-neutral human papillomavirus (HPV) immunization program in February 2014. In order to assure high coverage, factors influencing acceptance of the vaccine need to be identified. In this study we aim to assess parents' attitude and related socio-demographic factors in relation to the newly implemented gender-neutral, school-based HPV Immunization program. METHODS: Parents of 4th grade school children in 20 randomly selected primary schools were asked to fill out questionnaires on socio-demographic factors and on the level of information and attitude towards HPV infection and HPV vaccine. RESULTS: A total of 439 parents with 449 vaccine eligible children participated in the study. Fifty nine percent of vaccine eligible girls and 51.8% of eligible boys received the first dose of the vaccine. Fear of side effects and child being too young for the vaccine were the most commonly cited reasons by parents electing not to let child receive the vaccine. Children who had received other school-based vaccines have more than fifteen times higher probability of receiving HPV vaccine. To have received HPV-related information from physicians positively influenced vaccine acceptance (OR (95% CI)=1.60 (1.06-2.43)). Higher paternal (fathers') educational status significantly increased the chances of a male child to be HPV vaccinated (OR (95% CI)=2.45 (1.29-4.78)). CONCLUSION: Despite the efforts to provide HPV vaccine free-of-costs and as a school-based program, the study found that a significant proportion of vaccine eligible children failed to receive the vaccine. Involvement front line physicians and men with higher educational status may be utilised by public health policy makers in the effort to increase awareness. For a better acceptability of the vaccine, there is a need to consider lifting the age of "eligibility" for the school-based vaccination program.

The role of human papilloma virus in urological malignancies.

Human papillomavirus (HPV) is associated with cancer of the cervix uteri, penis, vulva, vagina, anus and oropharynx. However, the role of HPV infection in urological tumors is not yet clarified. HPV appears not to play a major causative role in renal and testicular carcinogenesis. However, HPV infection should be kept in mind regarding cases of prostate cancer, as well as in a sub-group of patients with bladder cancer with squamous differentiation. Concerning the role of HPV in penile cancer incidence, it is a recognized risk factor proven in a large number of studies. This short review provides an update regarding recent literature on HPV in urological malignancies, thereby, also discussing possible limitations on HPV detection in urological cancer.

Low prevalence of HPV detection and genotyping in non-muscle invasive bladder cancer using single-step PCR followed by reverse line blot.

PURPOSE: To clarify the role of human papillomavirus (HPV) in non-muscle invasive bladder cancer, HPV-DNA was scrutinized in formalin-fixed, paraffin-embedded (FFPE) bladder cancer tissue using single-step PCR (HPV L1) for HPV detection, followed by reverse line blot (RLB) for genotyping. METHODS: A total of 186 patients who underwent transurethral resection of the bladder due to primary, non-muscle invasive bladder cancer from 2006 to 2009 were reviewed. A positive control group of 22 cervical tissues with cervical carcinoma was included. RESULTS: Histology confirmed urothelial carcinoma in all patients: primary CIS, pTa, pT1 and pTa + pT1 in 14 (7.5 %), 134 (72 %), 36 (19.4 %) and two (1.1 %) patients, respectively. A total of 119 (63.9 %) of them were classified as low-risk, while 67 (36.1 %) were high-risk cancers. Tumor recurrence and progression (≥pT2) were seen in 79 and 11 patients (mean follow-up 45 months). The presence of HPV-DNA by single-step PCR was detected in four (2.2 %) patients. HPV 16 and HPV 6 were positive in two (1.1 %) and one (0.6 %) patient, respectively In one case, no HPV genotype listed on the RLB assay could be identified. In the control group, the HPV infection rate was 100 %: HPV 16 in 12 (54.6 %) patients, HPV 16/18 in four (18.3 %) patients, HPV 18 in two (9.1 %) patients, HPV 16/45 in one patient (4.5 %), HPV 18/33 in one (4.5 %) patient, HPV 16/33 in one (4.5 %) patient and HPV 33 in one (4.5 %) patient. CONCLUSIONS: Our study demonstrates low prevalence of HPV infection in FFPE bladder cancer tissue, arguing against the etiological role of HPV in non-muscle urothelial carcinogenesis.

A prospective study on metabolic risk factors and gallbladder cancer in the metabolic syndrome and cancer (Me-Can) collaborative study.

OBJECTIVE: To investigate the association between metabolic risk factors (individually and in combination) and risk of gallbladder cancer (GBC). METHODS: The metabolic syndrome and cancer project (Me-Can) includes cohorts from Norway, Austria, and Sweden with data on 578,700 men and women. We used Cox proportional hazard regression models to calculate relative risks of GBC by body mass index (BMI), blood pressure, and plasma levels of glucose, cholesterol, and triglycerides as continuous standardised variables and their standardised sum of metabolic syndrome (MetS) z-score. The risk estimates were corrected for random error in measurements. RESULTS: During an average follow-up of 12.0 years (SD = 7.8), 184 primary gallbladder cancers were diagnosed. Relative risk of gallbladder cancer per unit increment of z-score adjusted for age, smoking status and BMI (except for BMI itself) and stratified by birth year, sex and sub-cohorts, was for BMI 1.31 (95% confidence interval 1.11, 1.57) and blood glucose 1.76 (1.10, 2.85). Further analysis showed that the effect of BMI on GBC risk is larger among women in the premenopausal age group (1.84 (1.23, 2.78)) compared to those in the postmenopausal age group (1.29 (0.93, 1.79)). For the other metabolic factors no significant association was found (mid blood pressure 0.96 (0.71, 1.31), cholesterol 0.84 (0.66, 1.06) and serum triglycerides 1.16 (0.82, 1.64)). The relative risk per one unit increment of the MetS z-score was 1.37 (1.07, 1.73). CONCLUSION: This study showed that increasing BMI and impaired glucose metabolism pose a possible risk for gallbladder cancer. Beyond the individual factors, the results also showed that the metabolic syndrome as an entity presents a risk constellation for the occurrence of gallbladder cancer.

Total serum cholesterol and cancer incidence in the Metabolic syndrome and Cancer Project (Me-Can).

OBJECTIVE: To investigate the association between total serum cholesterol (TSC) and cancer incidence in the Metabolic syndrome and Cancer project (Me-Can). METHODS: Me-Can consists of seven cohorts from Norway, Austria, and Sweden including 289,273 male and 288,057 female participants prospectively followed up for cancer incidence (n = 38,978) with a mean follow-up of 11.7 years. Cox regression models with age as the underlying time metric were used to estimate hazard ratios (HR) and their 95% confidence intervals (CI) for quintiles of cholesterol levels and per 1 mmol/l, adjusting for age at first measurement, body mass index (BMI), and smoking status. Estimates were corrected for regression dilution bias. Furthermore, we performed lag time analyses, excluding different times of follow-up, in order to check for reverse causation. RESULTS: In men, compared with the 1st quintile, TSC concentrations in the 5th quintile were borderline significantly associated with decreasing risk of total cancer (HR = 0.94; 95%CI: 0.88, 1.00). Significant inverse associations were observed for cancers of the liver/intrahepatic bile duct (HR = 0.14; 95%CI: 0.07, 0.29), pancreas cancer (HR = 0.52, 95% CI: 0.33, 0.81), non-melanoma of skin (HR = 0.67; 95%CI: 0.46, 0.95), and cancers of the lymph-/hematopoietic tissue (HR = 0.68, 95%CI: 0.54, 0.87). In women, hazard ratios for the 5th quintile were associated with decreasing risk of total cancer (HR = 0.86, 95%CI: 0.79, 0.93) and for cancers of the gallbladder (HR = 0.23, 95%CI: 0.08, 0.62), breast (HR = 0.70, 95%CI: 0.61, 0.81), melanoma of skin (HR = 0.61, 95%CI: 0.42, 0.88), and cancers of the lymph-/hematopoietic tissue (HR = 0.61, 95%CI: 0.44, 0.83). CONCLUSION: TSC was negatively associated with risk of cancer overall in females and risk of cancer at several sites in both males and females. In lag time analyses some associations persisted, suggesting that for these cancer sites reverse causation did not apply.

Prospective cohort study of metabolic risk factors and gastric adenocarcinoma risk in the Metabolic Syndrome and Cancer Project (Me-Can).

PURPOSE: Little is known about the association between the metabolic syndrome (MetS) and the risk of gastric adenocarcinoma. The aim of this study was to investigate whether metabolic risk factors, together or combined, were associated with the risk of gastric adenocarcinoma. METHODS: The Metabolic Syndrome and Cancer Project (Me-Can) is a pooling of prospective cohorts in Austria, Norway, and Sweden with information on blood pressure, lipids, glucose, and BMI available in 578,700 individuals. Cox proportional hazards analysis was used to calculate hazard ratio (HR) of gastric adenocarcinoma using metabolic risk factors categorized into quintiles and transformed into z-scores (with mean = 0 and SD = 1). The standardized sum of all z-scores created a composite MetS score. RESULTS: In total, 1,210 incident cases of gastric adenocarcinoma were identified. Glucose was significantly associated with the risk of gastric adenocarcinoma [calibrated HR 1.58 (1.14-2.20) per one unit increment in z-score] in women. There was a statistically significant association between triglycerides and risk of gastric adenocarcinoma per mmol increment in triglycerides [HR 1.20 (1.06-1.36) per mmol] but not for the adjusted z-score in women. There were no significant association between any metabolic factors and gastric cancer among men. The composite MetS score was associated with the risk of gastric adenocarcinoma in women [HR 1.18 (1.00-1.38) per one unit increment in z-score] but not in men. CONCLUSIONS: Glucose and high levels of the composite MetS score were associated with an increased risk of gastric adenocarcinoma in women but not in men.

Metabolic risk factors and cervical cancer in the metabolic syndrome and cancer project (Me-Can).

BACKGROUND: Little is known about the association between metabolic risk factors and cervical cancer carcinogenesis. MATERIAL AND METHODS: During mean follow-up of 11 years of the Me-Can cohort (N=288,834) 425 invasive cervical cancer cases were diagnosed. Hazard ratios (HRs) were estimated by the use of Cox proportional hazards regression models for quintiles and standardized z-scores (with a mean of 0 and a SD of 1) of BMI, blood pressure, glucose, cholesterol, triglycerides and MetS score. Risk estimates were corrected for random error in the measurements. RESULTS: BMI (per 1SD increment) was associated with 12%, increase of cervical cancer risk, blood pressure with 25% and triglycerides with 39%, respectively. In models including all metabolic factors, the associations for blood pressure and triglycerides persisted. The metabolic syndrome (MetS) score was associated with 26% increased corrected risk of cervical cancer. Triglycerides were stronger associated with squamous cell carcinoma (HR 1.48; 95% CI, 1.20-1.83) than with adenocarcinoma (0.92, 0.54-1.56). Among older women cholesterol (50-70 years 1.34; 1.00-1.81), triglycerides (50-70 years 1.49, 1.03-2.16 and ≥70 years 1.54, 1.09-2.19) and glucose (≥ 70 years 1.87, 1.13-3.11) were associated with increased cervical cancer risk. CONCLUSION: The presence of obesity, elevated blood pressure and triglycerides were associated with increased risk of cervical cancer.