Erich V. Kliewer

Cancer risk in patients with inflammatory bowel disease

The objective of the current study was to determine the incidence of cancer among persons with inflammatory bowel disease (IBD) and to compare these incidence rates with those of the non‐IBD population using population‐based data from the administrative claims data of Manitobas universal provincial insurance plan (Manitoba Health).

Population-level impact and herd effects following human papillomavirus vaccination programmes: a systematic review and meta-analysis.

BACKGROUND Human papillomavirus (HPV) vaccination programmes were first implemented in several countries worldwide in 2007. We did a systematic review and meta-analysis to assess the population-level consequences and herd effects after female HPV vaccination programmes, to verify whether or not the high efficacy reported in randomised controlled clinical trials are materialising in real-world situations. METHODS We searched the Medline and Embase databases (between Jan 1, 2007 and Feb 28, 2014) and conference abstracts for time-trend studies that analysed changes, between the pre-vaccination and post-vaccination periods, in the incidence or prevalence of at least one HPV-related endpoint: HPV infection, anogenital warts, and high-grade cervical lesions. We used random-effects models to derive pooled relative risk (RR) estimates. We stratified all analyses by age and sex. We did subgroup analyses by comparing studies according to vaccine type, vaccination coverage, and years since implementation of the vaccination programme. We assessed heterogeneity across studies using I(2) and χ(2) statistics and we did trends analysis to examine the dose-response association between HPV vaccination coverage and each study effect measure. FINDINGS We identified 20 eligible studies, which were all undertaken in nine high-income countries and represent more than 140 million person-years of follow-up. In countries with female vaccination coverage of at least 50%, HPV type 16 and 18 infections decreased significantly between the pre-vaccination and post-vaccination periods by 68% (RR 0·32, 95% CI 0·19-0·52) and anogenital warts decreased significantly by 61% (0·39, 0·22-0·71) in girls 13-19 years of age. Significant reductions were also recorded in HPV types 31, 33, and 45 in this age group of girls (RR 0·72, 95% CI 0·54-0·96), which suggests cross-protection. Additionally, significant reductions in anogenital warts were also reported in boys younger than 20 years of age (0·66 [95% CI 0·47-0·91]) and in women 20-39 years of age (0·68 [95% CI 0·51-0·89]), which suggests herd effects. In countries with female vaccination coverage lower than 50%, significant reductions in HPV types 16 and 18 infection (RR 0·50, 95% CI 0·34-0·74]) and in anogenital warts (0·86 [95% CI 0·79-0·94]) occurred in girls younger than 20 years of age, with no indication of cross-protection or herd effects. INTERPRETATION Our results are promising for the long-term population-level effects of HPV vaccination programmes. However, continued monitoring is essential to identify any signals of potential waning efficacy or type-replacement. FUNDING The Canadian Institutes of Health Research.

Risk of second cancer among women with breast cancer

A large number of women survive a diagnosis of breast cancer. Knowledge of their risk of developing a new primary cancer is important not only in relation to potential side effects of their cancer treatment, but also in relation to the possibility of shared etiology with other types of cancer. A cohort of 525,527 women with primary breast cancer was identified from 13 population‐based cancer registries in Europe, Canada, Australia and Singapore, and followed for second primary cancers within the period 1943–2000. We used cancer incidence rates of first primary cancer for the calculation of standardized incidence ratios (SIRs) of second primary cancer. Risk of second primary breast cancer after various types of nonbreast cancer was also computed. For all second cancer sites combined, except contralateral breast cancer, we found a SIR of 1.25 (95% CI = 1.24–1.26) on the basis of 31,399 observed cases after first primary breast cancer. The overall risk increased with increasing time since breast cancer diagnosis and decreased by increasing age at breast cancer diagnosis. There were significant excesses of many different cancer sites; among these the excess was larger than 150 cases for stomach (SIR = 1.35), colorectal (SIR = 1.22), lung (SIR = 1.24), soft tissue sarcoma (SIR = 2.25), melanoma (SIR = 1.29), non‐melanoma skin (SIR = 1.58), endometrium (SIR = 1.52), ovary (SIR = 1.48), kidney (SIR = 1.27), thyroid gland (SIR = 1.62) and leukaemia (SIR = 1.52). The excess of cancer after a breast cancer diagnosis is likely to be explained by treatment for breast cancer and by shared genetic or environmental risk factors, although the general excess of cancer suggests that there may be additional explanations such as increased surveillance and general cancer susceptibility.

Risk of second primary cancer among patients with head and neck cancers: A pooled analysis of 13 cancer registries.

The objective of the study was to assess the risk of second primary cancers (SPCs) following a primary head and neck cancer (oral cavity, pharynx and larynx) and the risk of head and neck cancer as a SPC. The present investigation is a multicenter study from 13 population‐based cancer registries. The study population involved 99,257 patients with a first primary head and neck cancer and contributed 489,855 person‐years of follow‐up. To assess the excess risk of SPCs following head and neck cancers, we calculated standardized incidence ratios (SIRs) by dividing the observed numbers of SPCs by the expected number of cancers calculated from accumulated person‐years and the age‐, sex‐ and calendar period‐specific first primary cancer incidence rates in each of the cancer registries. During the observation period, there were 10,826 cases of SPCs after head and neck cancer. For all cancer sites combined, the SIR of SPCs was 1.86 (95% CI = 1.83–1.90) and the 20‐year cumulative risk was 36%. Lung cancer contributed to the highest proportion of the SPCs with a 20‐year cumulative risk of 13%. Excess second head and neck cancer risk was observed 10 years after diagnosis with lymphohaematopoietic cancers. The most common SPC following a first primary head and neck cancer was lung cancer. However, the highest excess of SPCs was in the head and neck region. These patterns were consistent with the notion that the pattern of cancer in survivors of head and neck cancer is dominated by the effect of tobacco smoking and alcohol drinking.

Population-Level Impact of the Bivalent, Quadrivalent, and Nonavalent Human Papillomavirus Vaccines: A Model–Based Analysis

BACKGROUND Bivalent and quadrivalent human papillomavirus (HPV) vaccines are now licensed in several countries. Furthermore, clinical trials examining the efficacy of a nonavalent vaccine are underway. We aimed to compare the potential population-level effectiveness of the bivalent, quadrivalent, and candidate nonavalent HPV vaccines. METHODS We developed an individual-based, transmission-dynamic model of HPV infection and disease in a population stratified by age, gender, sexual activity, and screening behavior. The model was calibrated to highly stratified sexual behavior, HPV epidemiology, and cervical screening data from Canada. RESULTS Under base case assumptions, vaccinating 12-year-old girls (70% coverage) with the bivalent (quadrivalent) vaccine is predicted to reduce the cumulative incidence of anogenital warts (AGWs) by 0.0% (72.1%), diagnosed cervical intraepithelial neoplasia lesions 2 and 3 (CIN2 and -3) by 51.0% (46.1%), and cervical squamous cell carcinoma (SCC) by 31.9% (30.5%), over 70 years. Changing from a bivalent (quadrivalent) to a nonavalent vaccine is predicted to reduce the cumulative number of AGW episodes by an additional 66.7% (0.0%), CIN2 and -3 episodes by an additional 9.3% (12.5%), and SCC cases by an additional 4.8% (6.6%) over 70 years. Differences in predicted population-level effectiveness between the vaccines were most sensitive to duration of protection and the time horizon of analysis. The vaccines produced similar effectiveness at preventing noncervical HPV-related cancers. CONCLUSIONS The bivalent vaccine is expected to be slightly more effective at preventing CIN2 and -3 and SCC in the longer term, whereas the quadrivalent vaccine is expected to substantially reduce AGW cases shortly after the start of vaccination programs. Switching to a nonavalent vaccine has the potential to further reduce precancerous lesions and cervical cancer.

Risk of Cervical Abnormalities in Women With Inflammatory Bowel Disease: A Population-Based Nested Case-Control Study

BACKGROUND & AIMS We evaluated the risk of cervical abnormalities in women with inflammatory bowel disease (IBD) in a population-based, nested, case-control study. METHODS Cases with abnormal Papanicolaou (Pap) smears or cervical biopsies were matched with up to 3 controls (normal Pap smears) by year of birth, year of first health care coverage, and number of Pap smears in the preceding 5 years. A diagnosis of IBD before the index date was identified from the University of Manitoba IBD Epidemiology Database. Exposures to immunosuppressant drugs and corticosteroids were determined from the provincial drug prescription database. Analyses were adjusted for socioeconomic status and exposure to oral contraceptives and nonsteroidal anti-inflammatory drugs. RESULTS 19,692 women with cervical cytologic and/or histologic abnormalities were matched with 57,898 controls with normal Pap smears. There was no association between cervical abnormalities and ulcerative colitis (odds ratio [OR], 1.03; 95% confidence interval [CI], 0.77-1.38). The increase in risk in women with Crohns disease was limited to those exposed to 10 or more prescriptions of oral contraceptives (OR, 1.66; 95% CI, 1.08-2.54). The combined exposure to corticosteroids and immunosuppressants was associated with increased risk of cervical abnormalities (OR, 1.41; 95% CI, 1.09-1.81). There was no interaction between the effect of IBD and corticosteroids and/or immunosuppressants. CONCLUSIONS These findings do not support an association between IBD itself and the risk of developing cervical abnormalities. An increased risk in patients given a combination of corticosteroids and immunosuppressants should be considered in managing women with IBD.

Disparities in mortality patterns among Canadian immigrants and refugees, 1980-1998: results of a national cohort study.

This study examines mortality patterns among Canadian immigrants, including both refugees and non-refugees, 1980–1998. Records of a stratified random sample of Canadian immigrants landing between 1980–1990 (N = 369,936) were probabilistically linked to mortality data (1980–1998). Mortality rates among immigrants were compared to those of the general Canadian population, stratifying by age, sex, immigration category, region of birth and time in Canada. Multivariate analysis examined mortality risks for various immigrant subgroups. Although immigrants presented lower all-cause mortality than the general Canadian population (SMR between 0.34 and 0.58), some cause-specific mortality rates were elevated among immigrants, including mortality from stroke, diabetes, infectious diseases (AIDS and hepatitis among certain subgroups), and certain cancers (liver and nasopharynx). Mortality rates differed by region of birth, and were higher among refugees than other immigrants. These results support the need to consider the heterogeneity of immigrant populations and vulnerable subgroups when developing targeted interventions.

Second primary cancers among 109 000 cases of non-Hodgkin's lymphoma

An analysis of other primary cancers in individuals with non-Hodgkins lymphoma (NHL) can help to elucidate this cancer aetiology. In all, 109 451 first primary NHL were included in a pooled analysis of 13 cancer registries. The observed numbers of second cancers were compared to the expected numbers derived from the age-, sex-, calendar period- and registry-specific incidence rates. We also calculated the standardised incidence ratios for NHL as a second primary after other cancers. There was a 47% (95% confidence interval 43–51%) overall increase in the risk of a primary cancer after NHL. A strongly significant (P<0.001) increase was observed for cancers of the lip, tongue, oropharynx*, stomach, small intestine, colon*, liver, nasal cavity*, lung, soft tissues*, skin melanoma*, nonmelanoma skin*, bladder*, kidney*, thyroid*, Hodgkins lymphoma*, lymphoid leukaemia* and myeloid leukaemia. Non-Hodgkins lymphoma as a second primary was increased after cancers marked with an asterisk. Patterns of risk indicate a treatment effect for lung, bladder, stomach, Hodgkins lymphoma and myeloid leukaemia. Common risk factors may be involved for cancers of the lung, bladder, nasal cavity and for soft tissues, such as pesticides. Bidirectional effects for several cancer sites of potential viral origin argue strongly for a role for immune suppression in NHL.

Second malignancies among survivors of germ-cell testicular cancer: A pooled analysis between 13 cancer registries

We investigated the risk of second malignancies among 29,511 survivors of germ‐cell testicular cancer recorded in 13 cancer registries. Standardized incidence ratios (SIRs) were estimated comparing the observed numbers of second malignancies with the expected numbers obtained from sex‐, age‐, period‐ and population‐specific incidence rates. Seminomas and nonseminomas, the 2 main histological groups of testicular cancer, were analyzed separately. During a median follow‐up period of 8.3 years (0–35 years), we observed 1,811 second tumors, with a corresponding SIR of 1.65 (95% confidence interval (CI): 1.57–1.73). Statistically significant increased risks were found for fifteen cancer types, including SIRs of 2.0 or higher for cancers of the stomach, gallbladder and bile ducts, pancreas, bladder, kidney, thyroid, and for soft‐tissue sarcoma, nonmelanoma skin cancer and myeloid leukemia. The SIR for myeloid leukemia was 2.39 (95% CI: 1.41–3.77) after seminomas, and 6.77 (95% CI: 4.14–10.5) after nonseminomas. It increased to 37.9 (95% CI: 18.9–67.8; based on 11 observed cases of leukemia) among nonseminoma patients diagnosed since 1990. SIRs for most solid cancers increased with follow‐up duration, whereas they did not change with year of testicular cancer diagnosis. Among subjects diagnosed before 1980, 20 year survivors of seminoma had a cumulative risk of solid cancer of 9.6% (95% CI: 8.7–10.5%) vs. 6.5% expected, whereas 20 years survivors of nonseminoma had a risk of 5.0% (95% CI: 4.2–6.0%) vs. 3.1% expected. In conclusion, survivors of testicular cancers have an increased risk of several second primaries, where the effect of the treatment seems to play a major role.

Epidemiology and costs associated with genital warts in Canada

Background: Genital warts (condyloma acuminatum) remain one of the most commonly reported sexually transmitted infections (STI) worldwide. Most genital warts are caused by non-oncogenic human papilloma virus. Recurrence is common and many patients receive several rounds of treatment. There are limited data in the literature on the burden of illness and costs associated with genital warts at a population level. Methods: Episodes of anogenital warts (AGW) were identified from the physician billing database, hospitalisation records and STI clinics from 1998 to 2006. To be included from the physician billing and STI databases, the person had to have a claim that had a diagnosis of condyloma acuminatum (078.11), viral warts (078.1), viral warts unspecified (078.10) or other unspecified warts (078.19), as well as one of the relevant fee codes associated with the treatment of AGW. To be included from the hospital database, the person could be of any age and have a diagnosis of AGW (A63.0), condyloma acuminatum (078.11), viral warts (078.1 or B07), viral warts unspecified (078.10) or other unspecified warts (078.19) in any of the diagnosis fields, as well as one of the relevant procedure codes associated with the treatment of AGW. Results: A total of 39 493 people was diagnosed with AGW and during this period they had a total of 43 586 episodes. The average cost per episode of AGW was