Incidence of NUT carcinoma in Western Australia from 1989 to 2014: a review of pediatric and adolescent cases from Perth Children's Hospital.

BACKGROUND: NUT carcinoma (NC), previously known as NUT midline carcinoma, is a rare and very aggressive cancer that occurs in both children and adults. NC is largely chemoresistant, with an overall survival of less than 7 months. Because the carcinoma is not restricted to a particular organ, diagnosis is often a challenge. In the absence of a clearly determined incidence for NC, we sought to study the diagnosis of patients in a well-defined population. METHODS: We systematically reviewed records of all patients that presented to the Oncology Department of the Princess Margaret Hospital for Children from 1989 to 2014. This institution in the geographically isolated state of Western Australia has a catchment population of around 2 million. We then identified all high grade undifferentiated sarcomas or carcinomas in the 0-16 year age group. RESULTS: Over 26 years, we found 14 patients of 16 years or younger with undifferentiated malignant tumors. Of these, five tumors were positive by immunohistochemistry for the NUT/NUTM1 (Nuclear Protein in Testis) protein and/or the translocation t(15;19). Three patients presented with thoracic tumors, one with a para-spinal tumor, and one had an upper airway nasopharyngeal carcinoma. In all five cases, there was an initial response to therapy and then progression. This 26-year survey was conducted in a geographically isolated state with a well-defined population, and we determined an estimated incidence of NC of around 0.41 per million child years (0-16 yrs. of age) at risk. From three patients it was feasible to derive cell lines for further genetic analyses and drug screening. CONCLUSIONS: For the first time, the incidence of NC could be determined in a well-defined geographic area. The calculated rate of NC incidence is consistent with a history of under-recognition for this malignancy. These findings indicate that improved diagnostic detection of NC would enable better management and counselling of patients. Our findings emphasize the heterogeneity of NC, and they highlight the need to develop personalised therapy options, and to consider a diagnosis of NC in undifferentiated malignant tumors.

Welding and the risk of head and neck cancer: the ICARE study.

OBJECTIVE: To investigate the association between occupational exposure to welding and the risk of head and neck cancer in a large French population-based case-control study, the Investigation of occupational and environmental CAuses of REspiratory cancers study. METHODS: Analyses were restricted to men (2703 controls and 1588 cases of squamous-cell carcinoma of the oral cavity, oropharynx, hypopharynx and larynx). Welding activity and potential confounders were assessed by detailed questionnaires. ORs and CIs (95% CI) were estimated by unconditional logistic regression, adjusted for age, area of residence, tobacco smoking, alcohol consumption and occupational exposure to asbestos. RESULTS: Welding was associated with an increased risk of head and neck cancer overall (OR=1.31, 95% CI 1.03 to 1.67). The association was strongest for laryngeal cancer (OR=1.66, 95% CI 1.15 to 2.38) and the risk increased with the cumulative duration (p-trend <0.01) and the weighted duration (p-trend <0.01) of welding. A cumulative duration and a weighted duration of welding of more than 10 years were also associated with a significantly increased risk of oral cancer (OR=1.82, 95% CI 1.09 to 3.04; OR=2.10, 95% CI 0.99 to 4.45, respectively). A long duration of arc welding was associated with laryngeal cancer, whereas a long duration of spot welding was associated with oral cancer. Welding was not associated with the risk of oropharyngeal and hypopharyngeal cancer. CONCLUSION: Our findings suggest that welding and several welding-related tasks increase the risk of laryngeal cancer and to a lesser extent oral cancer.

The relation between systemic inflammation and incident cancer in patients with stable cardiovascular disease: a cohort study.

AIMS: Low-grade inflammation, measured by elevated plasma concentrations of high-sensitive C-reactive protein (CRP), is a risk factor for cardiovascular disease (CVD). There is evidence that low-grade inflammation is also related to a higher risk of cancer. The present prospective cohort study evaluates the relation between low-grade systemic inflammation and risk of cancer in patients with stable CVD. METHODS AND RESULTS: In total, 7178 patients with stable CVD and plasma CRP levels ≤10 mg/L were included. Data were linked to the Dutch national cancer registry. Cox regression models were fitted to study the relation between CRP and incident CVD and cancer. After a median follow-up time of 8.3 years (interquartile range 4.6-12.3) 1072 incident cancer diagnoses were observed. C-reactive protein concentration was related to total cancer [hazard ratio (HR) 1.35; 95% confidence interval (CI) 1.10-1.65] comparing last quintile to first quintile of CRP. Especially lung cancer, independent of histopathological subtype, was related to CRP (HR 3.39; 95% CI 2.02-5.69 comparing last to first quintile of CRP). Incidence of epithelial neoplasms and especially squamous cell neoplasms were related to CRP concentration, irrespective of anatomical location. Sensitivity analyses after excluding patients with a cancer diagnosis within 1, 2, and 5 years of follow-up showed similar results. No effect modification was observed by smoking status or time since smoking cessation (P-values for interaction > 0.05). CONCLUSION: Chronic systemic low-grade inflammation, measured by CRP levels ≤10 mg/L, is a risk factor for incident cancer, markedly lung cancer, in patients with stable CVD. The relation between inflammation and incident cancer is seen in former and current smokers and is uncertain in never smokers.

A Meta-Analysis on Human Papillomavirus Type Distribution among Women with Cervical Neoplasia in the WHO Eastern Mediterranean Region.

INTRODUCTION: To date, the human papillomavirus (HPV) vaccine has not been integrated into the national vaccination program of most countries of the WHO Eastern Mediterranean Region (EMRO), except for the United Arab Emirates and Libya. The knowledge of HPV genotype distribution in cervical neoplasia is valuable to predict the impact of current HPV vaccines on cancer prevention and can help the health policymakers to select the most appropriate vaccine types in their countries. METHODS: Hence, this meta-analysis recapitulates all available data on HPV prevalence and genotypes in women with atypical squamous cells of undetermined significance (ASCUS), cervical intraepithelial neoplasia (CIN) I-III or low- and high-grade squamous intraepithelial lesions (LSIL and HSIL, respectively), and invasive cervical cancer (ICC) in EMRO countries. RESULTS: The meta-analysis included 5,990 cases of cervical precancer and cancer. The overall HPV prevalence was 85.4, 71.3, 59.2, and 34.8% in women with ICC, CIN II-III or HSIL, CIN I or LSIL, and ASCUS, respectively. HPV 16 was the most common genotype followed by HPV 18, representing 58 and 16.5% in ICC cases, respectively. CONCLUSION: This meta-analysis showed that the introduction of current HPV vaccines into national vaccination programs and the establishment of comprehensive screening programs in EMRO countries is beneficial by preventing 74.5% of cervical neoplasia.

Plasma selenoprotein P concentration and lung cancer risk: results from a case-control study nested within the Shanghai Men's Health Study.

Selenoprotein P (SELENOP) is a major selenoenzyme in plasma and linked to antioxidant properties and possibly to lung cancer; however, supporting evidence is limited. We investigated the association between pre-diagnostic plasma SELENOP concentration and lung cancer risk in a case-control study of 403 cases and 403 individually matched controls nested within the Shanghai Men's Health Study. SELENOP concentration in pre-diagnostic plasma samples was measured by a sandwich enzyme-linked immunosorbent assay. Cases were diagnosed with lung cancer between 2003 and 2010. Multivariate conditional logistic regression was used to estimate odds ratios (OR) and the corresponding 95% confidence intervals (CI) for studying the association between plasma SELENOP concentration and lung cancer risk. Cases had slightly lower plasma SELENOP concentration than controls (4.3 ± 1.2 versus 4.4 ± 1.1 mg/l, P difference = 0.09). However, the multivariate analysis showed no association between plasma SELENOP concentration and lung cancer risk among all participants (OR = 1.08, 95% CI = 0.54-2.14 for quartile 4 versus quartile 1), or by smoking status or tumor aggressiveness. In contrast, although the number of cases was limited, plasma SELENOP concentration was positively associated with lung adenocarcinoma risk (OR = 5.38, 95% CI = 1.89-15.35 for tertile 3 versus tertile 1), but not with squamous cell lung carcinoma (OR = 1.69, 95% CI = 0.43-6.70). Our study of adult men living in selenium non-deficient areas in China provides little support for the inverse association between pre-diagnostic plasma SELENOP concentration and lung cancer risk. Our finding of a positive association with risk of lung adenocarcinoma needs to be interpreted with caution.

Multidimensional analysis of the effect of occupational exposure to organic solvents on lung cancer risk: the ICARE study.

BACKGROUND: The association between lung cancer and occupational exposure to organic solvents is discussed. Since different solvents are often used simultaneously, it is difficult to assess the role of individual substances. OBJECTIVES: The present study is focused on an in-depth investigation of the potential association between lung cancer risk and occupational exposure to a large group of organic solvents, taking into account the well-known risk factors for lung cancer, tobacco smoking and occupational exposure to asbestos. METHODS: We analysed data from the Investigation of occupational and environmental causes of respiratory cancers (ICARE) study, a large French population-based case-control study, set up between 2001 and 2007. A total of 2276 male cases and 2780 male controls were interviewed, and long-life occupational history was collected. In order to overcome the analytical difficulties created by multiple correlated exposures, we carried out a novel type of analysis based on Bayesian profile regression. RESULTS: After analysis with conventional logistic regression methods, none of the 11 solvents examined were associated with lung cancer risk. Through a profile regression approach, we did not observe any significant association between solvent exposure and lung cancer. However, we identified clusters at high risk that are related to occupations known to be at risk of developing lung cancer, such as painters. CONCLUSIONS: Organic solvents do not appear to be substantial contributors to the occupational risk of lung cancer for the occupations known to be at risk.

Natural Antibodies to Human Papillomavirus 16 and Recurrence of Vulvar High-Grade Intraepithelial Neoplasia (VIN3).

OBJECTIVES: Approximately 30% of women treated for squamous high-grade intraepithelial neoplasia (VIN3), often associated with human papillomavirus (HPV), have recurrent disease. In this study, we assess predictors of recurrence that may provide targets for early prevention or treatment. MATERIALS AND METHODS: Women with VIN3 who participated in a previous population-based case-control study with blood and tumor samples completed a follow-up telephone interview an average of 5 years after initial diagnosis. The risk of recurrence was determined by proportional hazards modeling. RESULTS: Women with VIN3 in the follow-up study (n = 65) were similar to women with VIN3 in the parent study (n = 215) with regard to age at primary diagnosis, level of current cigarette smoking (>60%), and lifetime number of partners. We found that 22 (33.8%) of 65 participants had a vulvar recurrence and that 73.4% recurred within 3 years of treatment. Recurrences occurred more often among women with common warts in the decade before diagnosis (hazard ratio [HR] = 2.5, 95% CI = 1.1-5.8) and among those with a previous anogenital cancer (HR = 2.7, 95% CI = 1.2-6.3). Interestingly, recurrence was less frequent among women who mounted a natural antibody response to HPV16 (HR = 0.4, 95% CI = 0.2-0.9). CONCLUSIONS: These data provide strong preliminary evidence that VIN3 recurrence was less frequent among those with HPV16 antibodies. Vaccination with the currently licensed HPV vaccine as part of adjunctive therapy for VIN3 would increase antibody response and may decrease risk of recurrence. Randomized controlled trials are needed to determine whether HPV vaccination is effective against VIN3 recurrence.

Statin use is associated with reduced risk of histologic subtypes of esophageal cancer: a nested case-control analysis.

BACKGROUND & AIMS: Most patients with esophageal adenocarcinoma (EAC) or squamous cell cancer (ESCC) present with advanced, incurable disease. Statins have reported anti-carcinogenic effects and may be chemoprotective. We investigated the association between regular use of statins and the main histologic subtypes of esophageal malignancy (EAC, esophagogastric junctional adenocarcinoma, and ESCC) in the UK general population. METHODS: We identified all individuals in the UK General Practice Research Database diagnosed with esophageal cancer from 2000 through 2009. Patients were linked to the National Cancer Registry to confirm histologic subtypes. Each patient was matched with up to 4 controls for age, sex, and practice. We performed a nested case-control analysis using conditional logistic regression to estimate the risk of each subtype with regular statin use, adjusted for body mass index, smoking, alcohol intake, and concomitant use of medications. RESULTS: In total, 581 participants with EAC, 213 with esophagogastric junctional adenocarcinoma, and 332 with ESCC were matched to 2167, 783, and 1242 controls, respectively. Regular statin use was inversely associated with development of EAC (odds ratio = 0.58; 95% confidence interval: 0.39-0.87) (with significant dose and duration responses) and esophagogastric junctional adenocarcinoma (odds ratio = 0.29; 95% confidence interval: 0.09-0.92) (with high-dose use only). Statin use for 1-4 years was inversely associated with ESCC (odds ratio = 0.51; 95% confidence interval: 0.27-0.98). CONCLUSIONS: In a nested case-control analysis of a UK population-based cohort, statin use was inversely associated with histologic subtypes of esophageal cancer. Randomized controlled trials are warranted to determine whether statins have chemopreventive effects in high-risk groups.

Prevalence of sexually transmitted pathogens associated with HPV infection in cervical samples in a Mexican population.

Cervical cancer development has been mainly associated with persistent human papillomavirus (HPV) infections. However, HPV infection is unlikely to be sufficient to cause cervical cancer, and the contribution of other sexually transmitted infections (STIs) could be the determining factor for cervical lesion-progression. The aim of this study was to estimate the prevalence of STIs associated with HPV-positivity in 201 cervical samples from patients who underwent annual routine gynecological exams. The overall prevalence of STIs was 57.7%, and the most frequent infection was Ureaplasma spp (UP) (39.8%), followed by Gardnerella vaginalis (GV) (25.9%), α-HPV (18.4%), Chlamydia trachomatis (CT) (1.5%), and Mycoplasma genitalium (MG) (0.5%). The highest prevalence rate of multiple non-HPV infections was observed for the age-range 31-40; for papillomavirus infection, the age-range was 21-30. In normal cervical samples, HPV16 was the most prevalent genotype (24.3%), followed by genotypes 58 (13.5%) and 52 (10.8%). Intriguingly, HPV18 was not detected in the study population, and genotypes 52 and 58 were found exclusively in samples with abnormal cytology. Papillomavirus infection with oncogenic types was significantly associated with GV (P = 0.025) and strongly associated with multiple non-HPV pathogens (P = 0.002). The following variables correlated significantly with cytological diagnosis of low-grade squamous intraepithelial lesion (LSIL): GV (P = 0.028), multiple non-HPV infections (P = 0.001), and high-risk HPV positivity (P = 0.001). Epidemiological data from this study will contribute to the molecular detection of sexually transmitted pathogens from screening programs to identify those women who are at risk for developing cervical lesions.

Should endocervical curettage routinely be performed at the time of colposcopy? A cost-effectiveness analysis.

OBJECTIVES: Endocervical curettage (ECC) has been used with colposcopy-directed biopsy to increase diagnostic sensitivity for detecting cellular abnormality. Our objective was to determine if routine ECC was cost-effective compared with colposcopy alone in women with atypical squamous cells of undetermined significance or low-grade squamous intraepithelial lesion cervical cytology, who are older and younger than 50 years. MATERIALS AND METHODS: We generated a cost-effectiveness model using outcomes from cervical screening including repeat Pap smears, colposcopy, and loop electrosurgical excision procedure. Cervical cancer costs, survival, as well as incidence and complications after loop electrosurgical excision procedure (preterm birth, cervical stenosis, dysmenorrhea, amenorrhea, and infertility) were modeled. Cost and probability values were obtained from published literature and Medicare databases. Direct medical costs were analyzed in 2011 US dollars. Effectiveness outcomes were cervical cancer deaths and incident cases of cancer prevented. Model robustness was evaluated using probabilistic sensitivity analysis. RESULTS: For women older than 50 years, routine ECC is the dominant strategy (less expensive and more effective at reducing cervical cancer deaths/incidence). For women younger than 50 years, routine ECC costs $96,737 more per cervical cancer death prevented. Cost per incident cancer case prevented ranged from $21,894 (local spread or greater) to $235,873 (distal spread). Sensitivity analysis confirmed these conclusions. In women older than 50 years, routine ECC was always the most likely cost-effective choice. In women younger than 50, routine ECC was most likely cost-effective for all willingness-to-pay thresholds greater than $80,000 to prevent 1 cancer death. CONCLUSIONS: In women older than 50 years, routine ECC is favored over colposcopy alone because this strategy is cost saving and reduces the number of cancer deaths and incident cancer cases. For women younger than 50 years, cost-effectiveness is dependent on willingness to pay to prevent 1 cancer death but still seems to be cost-effective.

Natural immune responses against eight oncogenic human papillomaviruses in the ASCUS-LSIL Triage Study.

Only a subset of women with human papillomavirus (HPV) infections will become seropositive, and the factors influencing seroconversion are not well understood. We used a multiplex serology assay in women with mildly abnormal cytology results to examine seroreactivity to oncogenic HPV genotypes. An unbiased subset of women in the atypical squamous cell of undetermined significance /low-grade squamous intraepithelial lesion Triage Study provided blood samples at trial enrollment for serological testing. A Luminex assay based on glutathione s-transferase-L1 fusion proteins as antigens was used to test seroreactivity against eight carcinogenic HPV genotypes (16, 18, 31, 33, 35, 45, 52 and 58). We analyzed the relationship between seroprevalence in women free of precancer (N = 2,464) and HPV DNA status, age, sexual behavior and other HPV-related risk factors. The overall seroprevalence was 24.5% for HPV16 L1 and ∼20% for 18L1 and 31L1. Among women free of precancer, seroprevalence peaked in women less than 29 years and decreased with age. Type-specific seroprevalence was associated with baseline DNA detection for HPV16 (OR = 1.36, 95%CI: 1.04-1.79) and HPV18 (OR = 2.31, 95%CI: 1.61-3.32), as well as for HPV52 and HPV58. Correlates of sexual exposure were associated with increased seroprevalence across most genotypes. Women who were current or former smokers were less likely to be seropositive for all eight of the tested oncogenic genotypes. The multiplex assay showed associations between seroprevalence and known risk factors for HPV infection across nearly all tested HPV genotypes but associations between DNA- and serostatus were weak, suggesting possible misclassification of the participants' HPV serostatus.

HIV and HPV infections and ocular surface squamous neoplasia: systematic review and meta-analysis.

BACKGROUND: The frequency of ocular surface squamous neoplasias (OSSNs) has been increasing in populations with a high prevalence of infection with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) and infection with human papillomavirus (HPV). We aimed to quantify the association between HIV/AIDS and HPV infection and OSSN, through systematic review and meta-analysis. METHODS: The articles providing data on the association between HIV/AIDS and/or HPV infection and OSSN were identified in MEDLINE, SCOPUS and EMBASE searched up to May 2013, and through backward citation tracking. The DerSimonian and Laird method was used to compute summary relative risk (RR) estimates and 95% confidence intervals (95% CI). Heterogeneity was quantified with the I(2) statistic. RESULTS: HIV/AIDS was strongly associated with an increased risk of OSSN (summary RR=8.06, 95% CI: 5.29-12.30, I(2)=56.0%, 12 studies). The summary RR estimate for the infection with mucosal HPV subtypes was 3.13 (95% CI: 1.72-5.71, I(2)=45.6%, 16 studies). Four studies addressed the association between both cutaneous and mucosal HPV subtypes and OSSN; the summary RR estimates were 3.52 (95% CI: 1.23-10.08, I(2)=21.8%) and 1.08 (95% CI: 0.57-2.05, I(2)=0.0%), respectively. CONCLUSION: Human immunodeficiency virus infection increases the risk of OSSN by nearly eight-fold. Regarding HPV infection, only the cutaneous subtypes seem to be a risk factor.

Epidemiology of ocular surface squamous neoplasia in Africa.

OBJECTIVES: To describe the epidemiology and an aetiological model of ocular surface squamous neoplasia (OSSN) in Africa. METHODS: Systematic and non-systematic review methods were used. Incidence was obtained from the International Agency for Research on Cancer. We searched PubMed, EMBASE, Web of Science and the reference lists of articles retrieved. Meta-analyses were conducted using a fixed-effects model for HIV and cigarette smoking and random effects for human papilloma virus (HPV). RESULTS: The incidence of OSSN is highest in the Southern Hemisphere (16° South), with the highest age-standardised rate (ASR) reported from Zimbabwe (3.4 and 3.0 cases/year/100 000 population for males and females, respectively). The mean ASR worldwide is 0.18 and 0.08 cases/year/100 000 among males and females, respectively. The risk increases with exposure to direct daylight (2-4 h, OR = 1.7, 95% CI: 1.2-2.4 and ≥5 h OR = 1.8, 95% CI: 1.1-3.1) and outdoor occupations (OR = 1.7, 95% CI: 1.1-2.6). Meta-analysis also shows a strong association with HIV (6 studies: OR = 6.17, 95% CI: 4.83-7.89) and HPV (7 studies: OR = 2.64, 95% CI: 1.27-5.49) but not cigarette smoking (2 studies: OR = 1.40, 95% CI: 0.94-2.09). The effect of atopy, xeroderma pigmentosa and vitamin A deficiency is unclear. CONCLUSIONS: Africa has the highest incidence of OSSN in the world, where males and females are equally affected, unlike other continents where male disease predominates. African women probably have increased risk due to their higher prevalence of HIV and HPV infections. As the survival of HIV-infected people increases, and given no evidence that anti-retroviral therapy (ART) reduces the risk of OSSN, the incidence of OSSN may increase in coming years.

Mold infections in lung transplant recipients.

Fungal infections continue to produce morbidity and mortality in lung transplant recipients despite the widespread use of antifungal prophylaxis. There has been a decline in Candida infections but Aspergillus species predominate. Other mold pathogens including Fusarium, Scedosporium, and Zygomycetes also cause infections in lung transplant recipients. Furthermore, the widespread use of antifungal prophylaxis has prompted a delay in onset of Aspergillus infection in lung transplant recipients. Pulmonary parenchymal disease has become the most common manifestation of invasive aspergillosis. Among the risk factors pre- or posttransplant Aspergillus colonization is the most important risk factor reported in several retrospective studies. Recently posttransplant colonization has been implicated in the development of bronchiolitis obliterans syndrome. Other factors that have been reported include preceding cytomegalovirus infections, hypogammaglobulinemia, and single-lung transplantation. The risk factors for other mold infections such as Scedosporium, Fusarium, and Zygomycetes are not well studied. The best antimold prophylaxis strategy and choice of drug remains to be elucidated. Most lung transplant centers use either voriconazole or inhaled amphotericin preparations. However, data have emerged regarding the increased risk of squamous cell cancer in lung transplant recipients on voriconazole prophylaxis. Advances in the diagnosis and treatment of invasive aspergillosis have resulted in a significant decrease in mortality.

Squamous intraepithelial lesions in HIV-infected women: prevalence, incidence, progression and regression.

PURPOSE: To evaluate the impact of HIV immune depletion, highly active antiretroviral therapy (HAART) and patient characteristics on the occurrence of cervical squamous intraepithelial lesions (SIL). METHODS: A total of 898 HIV-positive women were evaluated at the time of their first Pap smear and 388 of them received additional Pap smears during follow-up in a cohort study. The patients were enrolled from July 1997 to April 2007. Prevalence and incidence of SIL in Pap smears were studied. Progression and regression were evaluated in follow-up of patients presenting low-grade SIL. RESULTS: Pap smear results at baseline were: 741 normal (82.5 %), 56 atypical squamous cells of indeterminate significance (ASCUS) (6.2 %), 78 low-grade SIL (8.7 %), 22 high-grade SIL (2.4 %), and 1 invasive cervical cancer (0.1 %). SIL cumulative incidence rate was 9.7 %. Progression and regression occurred in 15.9 and 62 %, respectively. Multivariate analysis of CD4 counts ≤ 200 cells/mm(3) (aHR = 2.1; 95 % CI 1.3-3.5; P = 0.004) and age less than 30 years (aHR = 3.2; 95 % CI 1.5-6.8; P = 0.01) or less than 40 years old (aHR = 2.6; 95 % CI 1.2-5.7; P = 0.01) were significantly associated with SIL prevalence. CD4 counts ≤ 200 cells/mm(3) (aHR = 3.0; 95 % CI 1.2-7.2; P = 0.01) and higher viral load counts (for each log increase) were associated with SIL incidence (aHR = 1.4; 95 % CI 1-1.9; P = 0.048). CONCLUSIONS: Prevalence and incidence of SIL in HIV-positive women were associated with severity of HIV disease. Interventions to increase access to Pap smears and further diagnostic tests should be implemented and targeted to HIV-positive women.

Increased risk of nonmelanoma skin cancers among individuals with inflammatory bowel disease.

BACKGROUND & AIMS: There are limited data on the risk of nonmelanoma skin cancer (NMSC) among individuals with inflammatory bowel disease (IBD), including those with or without exposure to immunosuppressant medications. METHODS: Individuals with IBD (n = 9618) were identified from the University of Manitoba IBD Epidemiology Database and matched with randomly selected controls (n = 91,378) based on age, sex, and postal area of residence on the date of IBD diagnosis (index date). Groups were followed up from the index date until a diagnosis of any invasive cancer (including NMSC), death, migration from the province, or the end of the study (December 31, 2009), whichever came first. Cox regression analysis was performed to calculate the relative risk of NMSC among the individuals with IBD, adjusting for frequency of ambulatory care visits and socioeconomic status. RESULTS: Of the individuals followed, 1696 were diagnosed with basal cell skin cancer (BCC) and 341 were diagnosed with squamous cell skin cancer (SCC). Individuals with IBD had an increased risk for BCC, compared with controls (hazard ratio, 1.20; 95% confidence interval [CI], 1.03-1.40). Among patients with IBD, use of thiopurines increased the risk of SCC (hazard ratio, 5.40; 95% CI, 2.00-14.56), compared with controls. Use of thiopurines also was associated with SCC in a case-control, nested analysis of individuals with IBD (odds ratio, 20.52; 95% CI, 2.42-173.81). CONCLUSIONS: The risk of BCC could be increased among individuals with IBD. Use of thiopurines increases the risk of SCC among individuals with IBD.

A large, population-based study of age-related associations between vaginal pH and human papillomavirus infection.

BACKGROUND: Vaginal pH is related to genital tract inflammation and changes in the bacterial flora, both suggested cofactors for persistence of human papillomavirus (HPV) infection. To evaluate the relationship between vaginal pH and HPV, we analyzed data from our large population-based study in Guanacaste, Costa Rica. We examined vaginal pH and the risk of HPV infection, cytological abnormalities, and C. trachomatis infection. METHODS: Our study included 9,165 women aged 18-97 at enrollment with a total of 28,915 visits (mean length of follow-up = 3.4 years). Generalized estimating equations were used to evaluate the relationship between vaginal pH and HPV infection (both overall and single versus multiple types) and low-grade squamous intraepithelial lesions (LSIL), the cytomorphic manifestation of HPV infection. The relationship between enrollment vaginal pH and C. trachomatis infection was assessed by logistic regression. Results were stratified by age at visit. RESULTS: Detection of HPV was positively associated with vaginal pH, mainly in women < 35 years (p-trend = 0.009 and 0.007 for women aged < 25 and 25-34 years, respectively). Elevated vaginal pH was associated with 30% greater risk of infection with multiple HPV types and with LSIL, predominantly in women younger than 35 and 65+ years of age. Detection of C. trachomatis DNA was associated with increased vaginal pH in women < 25 years (OR 2.2 95% CI 1.0-5.0). CONCLUSIONS: Our findings suggest a possible association of the cervical microenvironment as a modifier of HPV natural history in the development of cervical precancer and cancer. Future research should include studies of vaginal pH in a more complex assessment of hormonal changes and the cervicovaginal microbiome as they relate to the natural history of cervical neoplasia.

Ocular surface squamous neoplasia in New Zealand: a ten-year review of incidence in the Waikato region.

BACKGROUND: Ocular surface squamous neoplasia (OSSN) is a relatively rare disease with a low mortality and highly variable incidence. Despite a high incidence of OSSN in the Southern hemisphere, there is limited epidemiological data for New Zealand. The current study aims to assess the incidence, demographics, and histological grade of OSSN in the Waikato region of New Zealand, home to ~10% of the population of New Zealand. METHODS: Non-interventional retrospective cohort study. All conjunctival biopsy histology reports from 2010 to 2019 in the Waikato region of New Zealand were analysed. Age, sex, and ethnicity were analysed and the incidence of OSSN was calculated. Main outcome measures included histological grade, rate of recurrence, and incidence of OSSN. RESULTS: A total of 386 patients underwent conjunctival biopsy with histology during the study period. Eighty-three lesions (22%) involving 80 patients (21%) were reported positive for OSSN. Patients with OSSN had a mean age of 68.9 years (SD = 13.2), were predominantly male (76%), and of New Zealand-European ethnicity (53%). Conjunctival intraepithelial neoplasia-1 (30%) was the most frequent diagnosis. Three patients (4%) had recurrent lesions requiring repeat biopsy. The peak annual OSSN incidence rate was 3.81/100,000 population in 2019. The overall ten-year incidence was 2.13/100,000 population/year. CONCLUSION: This is the largest study to investigate OSSN incidence in New Zealand. The incidence rate of OSSN is one of the highest rates reported in the literature.

Trends in head and neck cancer incidence in Denmark, 1978-2007: focus on human papillomavirus associated sites.

The aim of our study was to assess the overall trends in the incidence of head-and-neck cancer (HNC) among Danish men and women in 1978-2007, to describe the distribution and incidences of HNCs at different anatomical sites, and to determine whether the incidence of human papillomavirus (HPV)-associated cancers is increasing. Data were extracted from the nationwide Cancer Registry database. To assess the possible impact of HPV infection, the sites of squamous cell carcinomas were categorized as HPV-associated, potentially HPV-associated or HPV-unrelated. In total, 26,474 incident cases were identified and the overall incidence increased throughout the period. Significantly increasing incidence rates were notably seen for tumors in the oral cavity (2.2% per year), tonsils (4.8% per year), oropharynx (3.5% per year) and hypopharynx (4.4% per year). A significantly decreasing incidence of lip cancer was observed among men (-5.0% per year). Cancers at HPV-associated sites (n = 3650) showed strongly increasing incidence rates, primarily in individuals < 60 years. In contrast, HNCs at sites not related to HPV infection showed a significant decrease (in men) or virtually no change in incidence (in women). Our results suggest a marked impact of HPV infection on the epidemiology of HNCs in Denmark. HPV16 is the type most often found in HNCs; thus, the recent introduction of vaccination against HPV may in the future prevent HPV-associated cancers of the head and neck.

Polymorphisms of MDM4 and risk of squamous cell carcinoma of the head and neck.

PURPOSE: Mouse double minute 4 (MDM4), a homolog of MDM2, is one of the key negative regulators of p53, and its amplification or overexpression contributes to carcinogenesis by inhibiting the p53 tumor suppressor activity. We investigated the association between MDM4 polymorphisms and the risk of squamous cell carcinoma of the head and neck (SCCHN). METHODS: We genotyped three MDM4 tagging polymorphisms, two in the 3' untranslated region (rs11801299G>A and rs10900598G>T) and one in intron 1 (rs1380576C>G), in a case-control study of 1075 non-Hispanic white SCCHN patients and 1079 cancer-free controls, and evaluated their associations with SCCHN risk. RESULTS: Although none of these three polymorphisms individually had a statistically significant effect on the risk of SCCHN, nor did their combined number of putative risk genotypes (i.e. rs11801299GG, rs1380576CG+GG, and rs10900598GG) [odds ratio (OR)=1.16; 95% confidence interval (95% CI) =0.93-1.45], we found that individuals with 1-3 risk genotypes had statistically significant increased risk of oropharyngeal cancer (OR=1.32; 95% CI=1.00-1.73), particularly for those with T1-2 stage (OR=1.40; 95% CI=1.02-1.94), those with regional lymph node metastases (N1-3) (OR=1.44; 95% CI=1.07-1.95), and those with late stages (III and IV) (OR=1.34; 95% CI=1.01-1.77). CONCLUSION: These results suggest that the joint effect of MDM4 variants may contribute to the risk of oropharyngeal cancer in non-Hispanic whites. Additional studies are warranted to unravel whether the particular stage distribution of oropharyngeal cancer with the strongest association (T1-2, N1-3, and III-IV) is a possible link with human papillomavirus-related oropharyngeal cancers.