Selected class I and class II HLA alleles and haplotypes and risk of high-grade cervical intraepithelial neoplasia.

Human leukocyte antigens (HLAs) present foreign antigens to the immune system and may be important determinants of cervical neoplasia. Previously published associations between HLA and cervical neoplasia exhibit considerable variation in findings. The biomarkers of cervical cancer risk (BCCR) case-control study addressed the role of specific HLA alleles as cofactors in the development of high-grade cervical intraepithelial neoplasia (HG-CIN) based on the most consistent evidence from published literature.

Human papillomavirus infection: epidemiology and pathophysiology.

More than 120 different types of the human papillomavirus (HPV) have been isolated; >40 of these types infect the epithelial lining of the anogenital tract and other mucosal areas. In the majority of individuals, HPV infections are transient and asymptomatic with most new infections resolving within 2 years. Epidemiological data from the U.

Human papillomavirus DNA versus Papanicolaou screening tests for cervical cancer.

Background: To determine whether testing for DNA of oncogenic human papillomaviruses (HPV) is superior to the Papanicolaou (Pap) test for cervical-cancer screening, we conducted a randomized trial comparing the two methods.

Methods: We compared HPV testing, using an assay approved by the Food and Drug Administration, with conventional Pap testing as a screening method to identify high-grade cervical intraepithelial neoplasia in women ages 30 to 69 years in Montreal and St. John's, Canada.

Haptoglobin phenotype and risk of cervical neoplasia: a case-control study.

Background: Haptoglobin is an acute-phase glycoprotein that influences host response to infections and tumours. The haptoglobin locus is polymorphic with 2 classes of alleles (Hp(1) and Hp(2)) yielding 3 phenotypes: Hp1-1, Hp2-2, and Hp2-1 with structurally and functionally distinct protein products, suggesting that haptoglobin polymorphism may influence susceptibility to infections and cancers.

Methods: We examined the relation between haptoglobin phenotype and high-grade cervical intraepithelial neoplasia (CIN) in a hospital-based case-control study.

Insulin-like growth factor-I and risk of high-grade cervical intraepithelial neoplasia.

Insulin-like growth factors (IGF) and their binding proteins (IGFBP) have been implicated in the risk of several epithelial or glandular tumors, including prostate cancer, breast cancer, and colon cancer. Cervical cancer, which is also of epithelial origin, has been shown to overexpress receptors for IGF-I, and plasma levels of IGF-I have been positively associated with cervical cancer precursors in one epidemiologic study. In this case-control study, we investigated plasma levels of IGF-I and IGFBP-3 in relation to the risk of histologically confirmed high-grade cervical intraepithelial neoplasia (HGCIN) and the risk of human papillomavirus (HPV) infection.

High grade cervical lesions are caused preferentially by non-European variants of HPVs 16 and 18.

The intratypic variability of HPVs 16 and 18 has been extensively studied and has been used as an important tool in epidemiological studies of viral transmission, persistence and progression to clinically relevant cervical lesions. Infections by non-European variants of HPVs 16 and 18 are associated with an increased risk for the development of high grade squamous intraepithelial lesions (HSIL). Our aim was to correlate the intratypic molecular variability of both HPV types and risk of persistent infection and lesion outcome in a cohort study conducted in Brazil.

Associations between serum carotenoids and tocopherols and type-specific HPV persistence: the Ludwig-McGill cohort study.

Although oncogenic HPV infections have been established as the necessary cause of cervical cancer, most HPV infections are transient and rarely progress to cervical lesions. Current research is focused on identifying factors associated with viral persistence and clearance, such as nutritional status. We evaluated the association between serum antioxidant nutrients (retinol, 10 carotenoids and 3 tocopherols) and type-specific HPV persistence over 4 visits among 405 women participating in the Ludwig-McGill cohort study.

Lack of agreement between cervicography and cytology and the effect of human papillomavirus infection and viral load.

Objective: Cohort studies of the natural history of human papillomavirus (HPV) infection and cervical squamous intraepithelial lesions with repeated screening allow the comparison of different macroscopic and microscopic diagnostic methods.

Materials And Methods: Concurrent visual inspection using cervicography and conventional Pap cytology tests were performed during multiple visits in a cohort of women attending a maternal and child health clinic in São Paulo, Brazil. HPV infection status at the same visits was determined by polymerase chain reaction followed by typing with specific oligonucleotide probing and viral load quantification.

Human papillomavirus infections with multiple types and risk of cervical neoplasia.

Background: Besides an established role for certain human papillomavirus (HPV) genotypes in the etiology of cervical cancer, little is known about the influence of multiple-type HPV infections on cervical lesion risk. We studied the association between multiple HPV types and cervical lesions among 2,462 Brazilian women participating in the Ludwig-McGill study group investigation of the natural history of HPVs and cervical neoplasia.

Methods: Cervical specimens were typed by a PCR protocol.

Randomized controlled trial of human papillomavirus testing versus Pap cytology in the primary screening for cervical cancer precursors: design, methods and preliminary accrual results of the Canadian cervical cancer screening trial (CCCaST).

Since infection with oncogenic human papillomavirus (HPV) has been considered a necessary cause of cervical cancer, tests for oncogenic HPV types have been proposed as adjuncts or replacements to Pap cytology. We designed the Canadian Cervical Cancer Screening Trial (CCCaST) to compare the relative efficacy of HPV DNA testing and Pap cytology in primary screening for cervical cancer and its high-grade precursors. CCCaST randomized women aged 30-69 years in Montreal (Quebec) and in St.

The p53 codon 72 polymorphism and risk of high-grade cervical intraepithelial neoplasia.

Background: The Arg/Arg genotype versus Arg/Pro or Pro/Pro at codon 72 of the p53 gene has been implicated in increasing susceptibility of the cervix to human papillomavirus (HPV) infection and thus altering cancer risk. However, research on this topic has been contentious, which prompted us to carry out a case-control study in the Montreal area.

Methods: Cases were women with histologically-confirmed high-grade cervical intraepithelial neoplasia (HGCIN).

Temporal variation and identification of factors associated with endogenous retinoic acid isomers in serum from Brazilian women.

Objective: Retinoids (natural and synthetic derivatives of vitamin A) have cancer chemotherapeutic and chemopreventive activities. Retinoic acid (RA) treatment has been associated with significant regression of preneoplastic lesions. However, serious toxicity associated with some therapies has made long-term chemoprevention in healthy populations unfeasible.

Other Gynecologic Cancers: endometrial, ovarian, vulvar and vaginal cancers.

HEALTH ISSUE: In Canada, cancers of the endometrium, ovaries, vulva, vagina, placenta and adnexa account for 11% of all malignant neoplasms in women and 81% of all genital cancers. Although the incidence and mortality from vulvar and vaginal cancers are very low, endometrium and ovarian cancer are important public health problems. KEY FINDINGS: In Canada, there has been no appreciable improvement in survival for women with advanced endometrial (EC) or ovarian cancer (OC) over the past 30 years.

Cancer of the Uterine Cervix.

HEALTH ISSUE: Cervical cancer is one of the most common malignant diseases of women; it is diagnosed in almost half a million women every year and half as many die from it annually. In Canada and other industrialized countries, its incidence has decreased due to cytology screening. However, invasive cases still occur, particularly among immigrant groups and native Canadian women.

Prospects for controlling cervical cancer at the turn of the century.

Cervical cancer morbidity and mortality have decreased substantially during the last 50 years mostly due to successful organized or opportunistic screening with Pap cytology in high and middle income countries. In many low income countries Pap cytology screening is yet to be effectively implemented or has failed to reduce cervical cancer rates to an appreciable extent. The fact that infection with certain human papillomavirus (HPV) types is now recognized as a necessary cause of this disease has led to new research fronts on prevention of cervical cancer.

Dietary intake and risk of persistent human papillomavirus (HPV) infection: the Ludwig-McGill HPV Natural History Study.

The association between dietary intake and persistence of type-specific human papillomavirus (HPV) infection, during a 12-month period, among 433 women participating in the Ludwig-McGill HPV Natural History Study was evaluated by use of a nested case-control design. Dietary intake was assessed by a food-frequency questionnaire at the month-4 visit. HPV status was assessed at months 0, 4, 8, and 12 by polymerase chain reaction (MY09/11).

Modeling the time dependence of the association between human papillomavirus infection and cervical cancer precursor lesions.

The authors studied the time-dependent association between human papillomavirus (HPV) infection and squamous intraepithelial lesions (SIL) among women enrolled in a cohort study in Brazil (1993-2002), using repeated Papanicolaou cytologic examination and HPV testing by polymerase chain reaction. Through simulation with conceivable alternative cohort designs, they investigated different regression modeling approaches using time-varying covariates, time-varying hazard ratio functions, and repeated events to assess the effect of delay in lesion detection. Associations between HPV and early SIL were of high magnitude.

Human papillomavirus infection and time to progression and regression of cervical intraepithelial neoplasia.

Background: Little is known about the duration of precancerous cervical lesions in relation to human papillomavirus (HPV) infection. We estimated rates of progression and regression and sojourn times of cervical squamous intraepithelial lesions (SILs) according to HPV status.

Methods: We used data from a longitudinal study of HPV infection and cervical neoplasia in São Paulo, Brazil.

Herpes simplex virus type II is not a cofactor to human papillomavirus in cancer of the uterine cervix.

Objective: Cells that were cotransfected with herpes simplex virus-16 and the herpes simplex virus type 2 Xho -2 DNA induce tumors in nude mice. In a cross-sectional study, we investigated the role of herpes simplex virus type 2 as a cofactor to human papillomavirus in cervical cancer.

Study Design: Cervical cells that were obtained with an endocervical Cytobrush brush (Medscand) from 439 women (50 women with cancer lesions, 65 women with high-grade squamous intraepithelial lesions, 80 women with low-grade squamous intraepithelial lesions, 244 healthy subjects) and DNA that was extracted from 150 cervical cancer biopsy specimens were analyzed with polymerase chain reaction for herpes simplex virus type 2 Xho -2 and Bgl IIC transforming DNA sequences.

Evidence-based policy recommendations on cancer screening and prevention.

Ideally, practice guidelines for cancer prevention should reflect the available empirical evidence. Although the most persuasive arguments for the efficacy of an intervention come from randomized controlled trials (RCTs), such studies are not always feasible because of ethical or logistical reasons. The advent of evidence-based medicine has underscored the need for consortia of researchers specialized in reviewing the biomedical literature on a systematic basis, ranking studies according to their design, quality, and generalizability of results.

Viral load as a predictor of the risk of cervical intraepithelial neoplasia.

HPV infections are believed to be a necessary cause of cervical cancer. Viral burden, as a surrogate indicator for persistence, may help predict risk of subsequent SIL. We used results of HPV test and cytology data repeated every 4-6 months in 2,081 women participating in a longitudinal study of the natural history of HPV infection and cervical neoplasia in São Paulo, Brazil.