Search PubMed⌕ Search

Biomedical subjects

Thomas C Wright

Publications and source records attributed to Thomas C Wright.

13 recordsLinked to original sources
PubMed2003

A comprehensive natural history model of HPV infection and cervical cancer to estimate the clinical impact of a prophylactic HPV-16/18 vaccine.

The object of our study is to project the impact of a prophylactic vaccine against persistent human papillomavirus (HPV)-16/18 infection on age-specific incidence of invasive cervical cancer. We developed a computer-based mathematical model of the natural history of cervical carcinogenesis to incorporate the underlying type-specific HPV distribution within precancerous lesions and invasive cancer. After defining plausible ranges for each parameter based on a comprehensive literature review, the model was calibrated to the best available population-based data. We projected the age-specific reduction in cervical cancer that would occur with a vaccine that reduced the probability of acquiring persistent infection with HPV 16/18, and explored the impact of alternative assumptions about vaccine efficacy and coverage, waning immunity and competing risks associated with non-16/18 HPV types in vaccinated women. The model predicted a peak age-specific cancer incidence of 90 per 100,000 in the 6th decade, a lifetime cancer risk of 3.7% and a reproducible representation of type-specific HPV within low and high-grade cervical precancerous lesions and cervical cancer. A vaccine that prevented 98% of persistent HPV 16/18 was associated with an approximate equivalent reduction in 16/18-associated cancer and a 51% reduction in total cervical cancer; the effect on total cancer was attenuated due to the competing risks associated with other oncogenic non-16/18 types. A vaccine that prevented 75% of persistent HPV 16/18 was associated with a 70% to 83% reduction in HPV-16/18 cancer cases. Similar effects were observed with high-grade squamous intraepithelial lesions (HSIL) although the impact of vaccination on the overall prevalence of HPV and low-grade squamous intraepithelial lesions (LSIL) was minimal. In conclusion, a prophylactic vaccine that prevents persistent HPV-16/18 infection can be expected to significantly reduce HPV-16/18-associated LSIL, HSIL and cervical cancer. The impact on overall prevalence of HPV or LSIL, however, may be minimal. Based on the relative importance of different parameters in the model, several priorities for future research were identified. These include a better understanding of the heterogeneity of vaccine response, the effect of type-specific vaccination on other HPV types and the degree to which vaccination effect persists over time.

Adolescent↗
PubMed2003

2001 consensus guidelines for the management of women with cervical intraepithelial neoplasia.

OBJECTIVE: The study was undertaken to provide consensus guidelines for the management of women with histologically confirmed cervical intraepithelial neoplasia (CIN) that can act as a precursor to invasive cervical cancer and represents one of the most common significant gynecologic diseases of women of reproductive age. PARTICIPANTS: An independent panel of 121 experts in various aspects of the diagnosis and management of cervical cancer precursors, including representatives from 29 participating professional organizations, federal agencies, national and international health organizations, and others were invited by the American Society for Colposcopy and Cervical Pathology (ASCCP). CONSENSUS PROCESS: Guidelines for the management of women with CIN were developed through a multistep process. Draft management guidelines were developed by working groups who performed formal literature reviews and obtained input from the professional community at large by way of an interactive internet-based bulletin board. At the ASCCP Consensus Conference, September 6 through 8, 2001, in Bethesda, Md, all guidelines were discussed, revised, and adopted by formal vote. CONCLUSION: Evidence-based guidelines have been developed for the management of women with biopsy-confirmed CIN.

Biopsy↗
PubMed2003

Chapter 10: Cervical cancer screening using visualization techniques.

There is a resurgence of interest in the use of visual techniques to identify cervical intraepithelial neoplasia (CIN). These visual techniques can be divided into two general categories. One is the simple visual screening method, such as direct visual inspection (DVI), during which the cervix is visualized with either the naked eye or a low-power magnification device after the application of a solution of 3% to 5% acetic acid that is used as a chemical contrast agent to highlight regions of CIN. DVI has been evaluated in a number of large clinical trials and is considered by some to be a possible alternative to cervical cytology for primary cervical cancer screening in low-resource settings. The advantages of DVI compared with cervical cytology for these settings are that it is inexpensive, it does not require a laboratory infrastructure, and it provides an immediate result, allowing the use of "screen and treat" protocols. The major disadvantage of DVI is that it is relatively nonspecific and that its sensitivity is low compared with testing for human papillomavirus. The other category of visual techniques includes devices that use electro-optical sensors and light of specific wavelengths produced by lasers or specialized light sources to identify and localize regions of CIN on the cervix. Although these "high-technology" devices are not yet in routine clinical use, several groups and companies have such devices in clinical trials.

Clinical Competence↗
PubMed2002

Cost-effectiveness of alternative triage strategies for atypical squamous cells of undetermined significance.

CONTEXT: Every year approximately 2 million US women are diagnosed as having a cervical cytological result of atypical squamous cells of undetermined significance (ASC-US). OBJECTIVE: To determine the most efficient and cost-effective management strategy for women in the United States diagnosed as having ASC-US. DESIGN AND SETTING: Cost-effectiveness analysis of data from clinical trials, prospective studies, and other published literature. A computer-based model was used to compare 4 management strategies for a cytological result of ASC-US: immediate colposcopy; human papillomavirus (HPV) triage, which includes colposcopy if high-risk HPV types are detected; repeat cytology, which includes follow-up cytology at 6 and 12 months and referral for colposcopy if a repeat abnormal result occurs; and reclassifying ASC-US as normal in which a cytological result of ASC-US is ignored. Reflex HPV DNA testing uses either residual liquid-based cytological specimens or samples co-collected at the time of the initial screening for conventional cytology. Another method, referred to as the 2-visit HPV DNA triage, requires a woman with an ASC-US result to return within 1 month to provide another speciman sample. MAIN OUTCOME MEASURES: Years of life saved (YLS), quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios. RESULTS: The least costly strategy for biennial screening was to reclassify ASC-US as normal, resulting in a reduction in total cancer incidence of 75% for conventional cytology and 84% for liquid-based cytology compared with no screening. The next least costly strategy was HPV DNA testing resulting in a reduction in total cancer incidence of 86% for conventional cytology and 90% for liquid-based cytology, followed by immediate colposcopy with a reduction of 87% and 91%, respectively. Compared with reflex HPV DNA testing, a strategy of repeat cervical cytology or delayed HPV testing costs more but is less effective. When all strategies were compared simultaneously, varying frequency and type of cytological test, biennial (vs every 3 years) liquid-based cytology with reflex HPV testing had a cost of $174 200 per YLS. In a similar comparison, liquid-based cytology with reflex HPV testing conducted every 3 years (vs every 5 years) had a cost of $59 600 per YLS and was more effective and less costly than a strategy of conventional cytology incorporating repeat cytology or immediate colposcopy conducted biennially. CONCLUSION: Reflex HPV DNA testing provides the same or greater life expectancy benefits and is more cost-effective than other management strategies for women diagnosed as having ASC-US.

Colposcopy↗
PubMed2002

2001 Consensus Guidelines for the management of women with cervical cytological abnormalities.

OBJECTIVE: To provide evidence-based consensus guidelines for the management of women with cervical cytological abnormalities and cervical cancer precursors. PARTICIPANTS: A panel of 121 experts in the diagnosis and management of cervical cancer precursors, including representatives from 29 professional organizations, federal agencies, and national and international health organizations, were invited to participate in a consensus conference sponsored by the American Society for Colposcopy and Cervical Pathology (ASCCP). EVIDENCE AND CONSENSUS PROCESS: Guidelines for the management of women with cervical cytological abnormalities were developed through a multistep process. Starting 6 months before the conference, working groups developed draft management guidelines based on formal literature reviews of English-language articles published in 1988-2001, as well as input from the professional community at large, obtained using interactive Internet-based bulletin boards. On September 6-8, 2001, the ASCCP Consensus Conference was held in Bethesda, Md. Guidelines with supporting evidence were presented and underwent discussion, revision, and voting. CONCLUSIONS: Management of women with atypical squamous cells (ASC) depends on whether the Papanicolaou test is subcategorized as of undetermined significance (ASC-US) or as cannot exclude high-grade squamous intraepithelial lesion (HSIL) (ASC-H). Women with ASC-US should be managed using a program of 2 repeat cytology tests, immediate colposcopy, or DNA testing for high-risk types of human papillomavirus (HPV). Testing for HPV DNA is the preferred approach when liquid-based cytology is used for screening. In most instances, women with ASC-H, low-grade squamous intraepithelial lesion, HSIL, and atypical glandular cells should be referred for immediate colposcopic evaluation.

Adolescent↗
PubMed2002

Direct visual inspection for cervical cancer screening: an analysis of factors influencing test performance.

BACKGROUND: The authors evaluated direct visual inspection of the cervix after the application of 5% acetic acid (DVI) as a cervical cancer screening test for use in low-resource settings. METHODS: Four tests were used to screen 2754 previously unscreened women: DVI with and without x4.5 magnification and differentiating between all lesions and well-circumscribed lesions; testing for high-risk types of human papillomavirus DNA using the Hybrid Capture II assay, cervical cytology, and Cervicography. Women with positive results on any of the four screening tests were referred for colposcopy and histologic sampling. All women were tested for N. gonorrhea, C. trachomatis, T. vaginalis, and human immunodeficiency virus 1. RESULTS: Histologically confirmed carcinoma was diagnosed in 21 women (0.8%), high-grade squamous intraepithelial lesions (SILs) were diagnosed in 96 women (3.5%), and low-grade SILs were diagnosed in 102 women (3.7%). The estimated sensitivity of DVI when performed without magnification for high-grade SILs was 70%, with an estimated specificity of 79%. Magnification did not significantly improve sensitivity for high-grade SILs (74% with magnification) but significantly reduced specificity (77%). Restricting the definition of a positive DVI test to a well-defined acetowhite lesion reduced sensitivity and significantly improved specificity. Infection with T. vaginalis, N. gonorrhea, and C. trachomatis did not alter sensitivity or specificity. CONCLUSIONS: This study confirmed the utility of DVI as a primary screening test. Evaluation of the clinical effectiveness of screening with this low-cost and simple test in low-resource settings is necessary.

Acetic Acid↗
PubMed2002

HIV-1 infection and risk of vulvovaginal and perianal condylomata acuminata and intraepithelial neoplasia: a prospective cohort study.

BACKGROUND: Information about vulvovaginal and perianal condylomata acuminata and intraepithelial neoplasia in women infected with HIV-1 is needed to develop guidelines for clinical care. Our aim was to investigate the incidence of these lesions in HIV-1-positive and HIV-1-negative women and to examine risk factors for disease. METHODS: In a prospective cohort study, 925 women had a gynaecological examination twice yearly-including colposcopy and tests for human papillomavirus DNA in cervicovaginal lavage-for a median follow-up of 3.2 years (IQR 0.98-4.87). FINDINGS: Vulvovaginal and perianal condylomata acuminata or intraepithelial neoplasia were present in 30 (6%) of 481 HIV-1-positive and four (1%) of 437 HIV-1-negative women (p<0.0001) at enrollment. Women without lesions at enrollment were included in an incidence analysis. 33 (9%) of 385 HIV-1-positive and two (1%) of 341 HIV-1-negative women developed vulvovaginal or perianal lesions, resulting in an incidence of 2.6 and 0.16 cases per 100 person-years, respectively (relative risk 16, 95% CI 12.9-20.5; p < 0.0001). Risk factors for incident lesions included HIV-1 infection (p = 0.013), human papillomavirus infection (p=0.0013), lower CD4 T lymphocyte count (p = 0.0395), and history of frequent injection of drugs (p=0.0199). INTERPRETATION: Our results suggest that HIV-1-positive women are at increased risk of development of invasive vulvar carcinoma. Thus, we recommend that, as part of every gynaecological examination, HIV-1-positive women should have a thorough inspection of the vulva and perianal region, and women with abnormalities-except for typical, exophytic condylomata acuminata-should undergo colposcopy and biopsy.

AIDS-Related Opportunistic Infections↗
PubMed2002

The menstrual cycle does not affect human immunodeficiency virus type 1 levels in vaginal secretions.

To determine whether the menstrual cycle affects human immunodeficiency virus (HIV) type 1 levels in vaginal secretions, vaginal lavage samples were collected at 7, 14, and 21 days after initiation of menses, to compare virus levels during the follicular, ovulatory, and luteal phases. During 33 menstrual cycles in 25 women, HIV-1 RNA levels in vaginal secretions ranged from <1000 to 5.3x10(7) copies per lavage, and weekly changes ranged from <0.5 to 2.5 log(10) copies per lavage. HIV-1 RNA levels in vaginal lavage samples from days 7, 14, and 21 were not significantly different. No discernible pattern was found in changes of vaginal virus loads (VVLs) during the menstrual cycle. VVLs were not correlated with plasma estradiol or progesterone levels (P>.05). These results suggest that hormonal changes during the menstrual cycle do not have a significant effect on HIV-1 RNA levels in vaginal secretions.

Adolescent↗
PubMed2002

Use of visual screening methods for cervical cancer screening.

This article has considered recent advances in visual screening methods. Devices that use electro-optical sensors offer great potential in various clinical roles, but considerable additional work is required to develop these devices and it is unlikely that they will come into widespread clinical use in the next 5 years. In contrast numerous studies, demonstrate that simple visual screening methods, such as DVI, have a sensitivity for the detection of women with biopsy-confirmed high-grade SIL (CIN 2,3) and cancer that is equivalent to that of conventional cervical cytology. The primary disadvantage of the simple visual screening methods is poor specificity. These methods classify up to 30% of all women screened as being test positive and as a result new strategies toward managing DVI positive women must be developed before simple visual screening methods can be adopted for routine screening. Enhanced visual methods that use cervicography and speculoscopy may be more specific and improve detection of biopsy-confirmed SIL, but the added time and expense to perform either of these methodologies must be considered and justified. Currently numerous studies are evaluating the best strategies for incorporating visual screening methods into cervical cancer screening programs. In the near future we should be able to determine whether these approaches should be incorporated into routine clinical care.

Acetic Acid↗
PubMed2002

Can cervicography be improved? An evaluation with arbitrated cervicography interpretations.

OBJECTIVE: The purpose of this study was to estimate the optimal performance of cervicography. We compared an arbitrated cervigram classification with an arbitrated referent diagnosis of cervical neoplasia. STUDY DESIGN: From an initial group of 8460 women, a stratified sample of cervigrams from 3645 women and histologic information from 414 women underwent arbitration. Interobserver agreement was assessed for cervicography and the referent diagnosis. Sensitivity, specificity, and predictive values were estimated for initial and arbitrated cervicography results, compared with the initial and arbitrated referent diagnoses. RESULTS: For the detection of arbitrated high-grade lesions or cancer, arbitrated cervicography yielded an overall sensitivity of 63.9% and a specificity of 93.7%. Significantly higher sensitivity was associated with younger age and age-related visual characteristics. CONCLUSION: Optimization of the cervigram classification improved performance over a single interpretation in this population but suggested the limits of static visual screening.

Colposcopy↗
PubMedDate not supplied

Visualization techniques (colposcopy, direct visual inspection, and spectroscopic and other visual methods). Summary of task force 7.

Visual screening techniques include both low-technology approaches, such as direct visual inspection (DVI), and high-technology approaches, such as those that utilize electrooptical detectors to identify cervical cancer precursors and invasive cervical cancer. Simple visual screening techniques, such as DVI, consist of washing the cervix with a solution of 5% acetic acid (e.g., vinegar) and then inspecting it using either the naked eye or with a low-power magnifying device to identify areas of acetowhitening, which frequently correspond to cervical squamous intraepithelial lesions (SILs). The simple visual screening methods are being evaluated as an alternative to cytology in low-resource settings where screening using cervical cytology is not feasible. Multiple studies have shown DVI to have sensitivity similar to that of cervical cytology for identifying women with high grade SIL but much lower specificity. The novel high-technology visual screening methods that utilize electrooptical sensors to identify cervical abnormalities are still in the developmental phases but offer considerable potential.

Acetic Acid↗