Andrea Spence

The Role of Human Papillomaviruses in Cancer

The human papillomavirus (HPV) has been implicated in the development of an estimated 10% of cancers worldwide. Both epidemiologic and molecular evidence have conclusively demonstrated that oncogenic HPV is the central causal agent of cervical cancer and of a substantial proportion of many other anogenital neoplasms. In fact, it is believed that HPV is the necessary cause of cervical cancer, which has implications for the prevention, screening, and treatment of this disease, especially for its precursor lesions.This has led to the possibility of using HPV DNA testing in screening and as a method of triaging abnormal Papanicolaou (Pap) tests. Research into the development of vaccines is also currently very active. HPV has been implicated in the genesis of several other cancers, such as oral and non-melanoma skin malignancies. However, research is yet to provide a consistent body of unequivocal evidence for a causal role that could lead to public health policy.

Laparoscopic and robot-assisted hysterectomy for uterine cancer: a comparison of costs and complications

OBJECTIVE Increasingly, robotic surgery is being used for total hysterectomy, bilateral salpingo-oophorectomy, and lymph node dissection for uterine cancer. The purpose of this study was to compare the costs and complications among women undergoing robotic and laparoscopic hysterectomy for uterine cancer. STUDY DESIGN We carried out a cohort study using the Nationwide Inpatient Sample (NIS) database between 2008 and 2012 on all women diagnosed with uterine cancer, classifying women as either laparoscopically or robotically treated, excluding laparotomies or vaginal approaches. Logistic regression analyses were used to evaluate the adjusted effect of surgical approach on complication rates. RESULTS There were 10,347 women who underwent hysterectomies for uterine cancer either laparoscopically (39%) or robotically (61%). The rate of robotic surgery consistently increased over the 5 year period. Women undergoing robotic surgery had more comorbid conditions (diabetes, hypertension, cardiovascular disease, renal disease, obesity or morbid obesity, and pulmonary disease). In adjusted analyses, women undergoing robotic surgery were more likely to have a lymph node dissection (73.01% vs 66.04%; P < .0001) and an admission lasting <3 days (86.01% vs 82.5%; P < .0001) compared with those undergoing laparoscopic surgery. The composite endpoint of any complication was similar between both cohorts (20.56% robotic vs 21.00% laparoscopy). In overall and subset analyses, robotic surgery was more costly, with median charges of

Commentary: Smoking and human papillomavirus infection: the pursuit of credibility for an epidemiologic association

38,161.00 compared with

Screening histories and contact with physicians as determinants of cervical cancer risk in Montreal, Quebec.

31,476.00 in those undergoing laparoscopic surgery (P < .0001). CONCLUSION Despite the considerably greater burden of comorbidities in those undergoing robotic surgery compared with laparoscopy, the former have shorter hospital admissions, a greater rate of lymph node dissection, and similar postoperative morbidity and mortality, albeit at greater total cost.

Hysterectomy for Uterine Cancer in the Elderly: A Comparison Between Laparoscopic and Robot-Assisted Techniques.

As the most important among the modifiable risk factors for many cancer types tobacco smoking is dutifully treated as a potent confounder when epidemiologists explore new candidate relations. The role for smoking changes from ‘confounder’ to ‘confounded’ variable in anogenital cancers. Among the latter, cervical cancer is a case in point. Smoking was first suspected as a risk factor for cervical cancer in the mid 60s but although most studies have replicated the finding the association was always seen with suspicion because of confounding by sexual activity. Number of sexual partners and age at first intercourse are unequivocal key determinants of risk, which has long suggested that an infectious sexually-transmitted agent plays an aetiological role. Controlling for these two measures of sexual behaviour tended to dampen the associations with smoking in cervical cancer studies but in many of them it remained statistically detectable. Concerns about residual confounding by unmeasured sexual behaviours or insufficient control of confounding due to misclassification of sexual activity information led the International Agency for Research on Cancer (IARC) to defer judgment about a carcinogenic role for smoking in cervical cancer in its first monograph focusing on tobacco products in 1986. This intractable situation was nicely captured in 1994 in an insightful article in the Journal which demonstrated that, as long as the putative sexuallytransmitted aetiologic agent remained unmeasured and uncontrolled for in an epidemiological study, the association with smoking would continue to be hopelessly confounded, despite best efforts at adjusting for sexual activity variables. It did not help when the first molecular epidemiologic studies in the late 80s heeded this advice by placing the human papillomavirus (HPV) at centre stage for the first time. Paradoxically, HPV infection measured in these earlier studies was not associated with sexual activity and was only feebly associated with cervical cancer. Epidemiologists learned that misclassification of HPV status could account for the incoherent results and were quick to adopt improved molecular techniques for detecting HPV, which led to the recognition of this virus as a necessary cause of cervical cancer and ushered in a new era in cervical cancer prevention via HPV vaccination and screening with HPV tests. Once measurement error issues related to cervical HPV detection were largely resolved the smoking-cervical cancer association could be verified with reasonable confidence. The IARC revisited its previous conclusions and listed cervical cancer among those causally related to smoking in 2004. A pooled analysis of 23 modern molecular epidemiologic studies that included over 13 000 cases and 23 000 controls and carefully controlled for HPV status found an increased risk of squamous cell carcinomas with a dose–response relation with number of cigarettes. Although the controversy subsided, the role of epidemiology was not yet over; a mechanism for the carcinogenic action of tobacco smoking needed to be documented. The aetiological pathway that begins with sexual activity as distal variable, then includes HPV infection as intermediate endpoint, and ends with cervical cancer is consistent with both ‘upstream’ and ‘downstream’ smoking effects relative to HPV infection. Documenting both still requires careful attention to confounding by sexual activity, which is strongly correlated with smoking habits. In this issue of the Journal, Vaccarella et al. advanced our understanding of the upstream relation by focusing on smoking as a determinant of HPV infection in the large IARC multi-centre study of HPV prevalence, which included over 10 000 women throughout the world. Their state-of-the-art methods for detecting HPV DNA in cervical specimens were conducted in world-class laboratories. The authors were acutely aware of the confounding problem and made clever use of the standardized questionnaire information to control for age, number of sexual * Corresponding author. Department of Epidemiology & Biostalistics and Department of Oncology, McGill University, Montreal, Canada. E-mail: eduardo.franco@mcgill.ca Department of Epidemiology & Biostatistics and Department of Oncology, McGill University, Montreal, Canada. Published by Oxford University Press on behalf of the International Epidemiological Association

Pregnancy outcomes among women with asthma

BACKGROUND Cervical cancer (cca) is largely a preventable disease if women receive regular screening, which allows for the detection and treatment of preinvasive lesions before they become invasive. Having been inadequately screened is a common finding among women who develop cca. Our primary objective was to determine the Pap screening histories of women diagnosed with cca in Montreal, Quebec. Secondary objectives were to determine the characteristics of women at greatest risk of cca and to characterize the level of physician contact those women had before developing cca. METHODS The Invasive Cervical Cancer Study, a population-based case-control study, consisted of Greater Montreal residents diagnosed with histologically confirmed cca between 1998 and 2004. Respondents to the 2003 Canadian Community Health Survey and a sample of women without cca obtained from Quebec medical billing records served as controls. RESULTS During the period of interest, 568 women were diagnosed with cca. Immigrants and women speaking neither French nor English were at greatest risk of cca. Most of the women in the case group had been screened at least once during their lifetime (84.8%-90.4%), but they were less likely to have been screened within 3 years of diagnosis. Having received care from a family physician or a medical specialist other than a gynecologist within the 5 years before diagnosis was associated with a greater risk of cca development. CONCLUSIONS Our findings provide evidence of the need for an organized population-based screening program. They also underscore the need for provider education to prevent missed opportunities for cca screening when at-risk women seek medical attention.

Pregnancy Outcomes in Women with Rheumatoid Arthritis: A Retrospective Population-Based Cohort Study [7N]

Objective The mainstay of treatment for uterine corpus cancer is surgical, and the gold standard approach has become minimally invasive surgery. The aim of this study is to compare the perioperative complications and demographics of patients 80 years old or more undergoing robotic and laparoscopic hysterectomy for uterine cancer. Materials and Methods Using the Nationwide Inpatient Sample, we retrospectively identified all women aged 80 years or older who had hysterectomies for uterine cancer by either modality. The complication rates of surgery in both groups were adjusted for potential confounding and compared using logistic regression analyses. Results There were 915 women aged 80 years or older identified with uterine corpus cancer who had either laparoscopic or robotic surgery. Robotically treated patients were more likely to be obese (8.8% vs 3.5%) but were otherwise similar in terms of mean age, comorbidities, income, ethnicity, and insurance status. Those undergoing robotic surgery were less likely to have admissions beyond 3 days (29.0% vs 38.2%; adjusted odds ratio, 0.66; P < 0.01) and had a lower composite incidence of any complication (24.3% vs 31.6%; adjusted odds ratio, 0.7; P < 0.05). When looking at those who had lymph node dissections, there was a lower rate of postoperative ileus, and a trend toward fewer venous thromboembolic events. Conclusions Among octogenarians and nonagenarians with uterine corpus cancer, robotic surgery is associated with a shorter hospital admission and a better complication profile than laparoscopy.

Effect of pre-pregnancy body mass index on respiratory-related neonatal outcomes in women undergoing elective cesarean prior to 39 weeks

Abstract Purpose: The purpose of this study is to examine the association between maternal asthma and pregnancy, delivery and neonatal outcomes. Materials and methods:We carried out a retrospective cohort study using the Health Care Cost and Utilization Project-Nationwide Inpatient Sample (HCUP-NIS) database from 2003 to 2011. Among women who delivered during this time period, we compared pregnancy, delivery, and neonatal outcomes in asthmatics versus non-asthmatics. Multivariate logistic regression was used to estimate adjusted odds ratios and 95% confidence intervals. Results: In a cohort of 7,772,999 pregnant women, 223,236 (2.9%) had asthma. The prevalence of asthma-complicated pregnancies rose over the study period from 1.9% in 2003 to 3.7% in 2011 (p < .001). Pregnant asthmatics had more pre-existing health conditions, such as diabetes, chronic hypertension, obesity, and thyroid disease, and were more likely to smoke. Even after adjustment for these comorbidities, and other covariates, within statistical models, asthma was found to be associated with greater risk of several pregnancy complications: gestational hypertension, preeclampsia, gestational diabetes, placenta previa, preterm premature rupture of membranes, placental abruption, chorioamnionitis, preterm delivery, postpartum hemorrhage, venous thromboembolism, caesarean section delivery, and maternal mortality. Neonates born to asthmatics had greater risk of being small for gestational age and for having congenital anomalies, and lower risk of intrauterine fetal death. Conclusions: Asthma is associated with an increase in adverse pregnancy, labor, and neonatal outcomes. Close surveillance of asthmatic patients during the prenatal period is warranted and care in a tertiary hospital is advised.

Incidence and Causes of Maternal Mortality in the Unites States [294]

INTRODUCTION:Rheumatoid arthritis (RA) is a chronic autoimmune, inflammatory disease that is more commonly found in women. Our objective is to assess if pregnancies in women with RA are at a higher risk of adverse maternal and neonatal outcomes.METHODS:We carried out a retrospective cohort study, us

Process of care failures in invasive cervical cancer: systematic review and meta-analysis.

Abstract Objective To examine the association between pre-pregnancy body mass index (BMI) and neonatal respiratory-related outcomes among women who underwent an elective cesarean section (CS). Methods A retrospective cohort study was conducted using the Centers for Disease Control and Prevention (CDC)’s 2009–2013 period linked birth/infant death dataset. Women who had elective CSs at term were categorized by their pre-pregnancy BMI as normal, overweight, obese or morbidly obese. Odds ratios (OR) and 95% confidence intervals (CIs), adjusted for baseline characteristics, were calculated using multivariate logistic regression to estimate the neonatal risks in relation to maternal pre-pregnancy BMI. Results Our cohort consisted of 717,080 women, of whom 39.9% had normal BMI, 27.0% were overweight, 25.7% obese and 7.4% morbidly obese. A dose-dependent relationship between maternal pre-pregnancy BMI and assisted ventilation was seen. Furthermore, infants born to morbidly obese women were at significantly increased risk for assisted ventilation over 6 h (OR 1.24, 95% CI 1.15–1.35) and admission to intensive care units (OR 1.17, 95% CI 1.13–1.21). Infant mortality rates were 4.2/1000 births for normal weight women, and 5.5/1000 births among the morbidly obese group (OR 1.43, 95% CI 1.25–1.64). Risk for adverse outcomes was increased with elective SC performed at earlier gestational age, and this effect was not modified by use of corticosteroids. Conclusion Overweight and obese women are at particularly greater risk of adverse newborn outcomes when elective CSs are done before 39 weeks. In these women, elective CSs should be delayed until 39 weeks, as corticosteroid use did not eliminate this association.