Epidemiologic natural history and clinical management of Human Papillomavirus (HPV) Disease: a critical and systematic review of the literature in the development of an HPV dynamic transmission model

<p>Abstract</p> <p>Background</p> <p>Natural history models of human papillomavirus (HPV) infection and disease have been used in a number of policy evaluations of technologies to prevent and screen for HPV disease (e.g., cervical cancer, anogenital warts), sometimes with wide variation in values for epidemiologic and clinical inputs. The objectives of this study are to: (1) Provide an updated critical and systematic review of the evidence base to support epidemiologic and clinical modeling of key HPV disease-related parameters in the context of an HPV multi-type disease transmission model which we have applied within a U.S. population context; (2) Identify areas where additional studies are particularly needed.</p> <p>Methods</p> <p>Consistent with our and other prior HPV natural history models, the literature review was confined to cervical disease and genital warts. Between October 2005 and January 2006, data were gathered from the published English language medical literature through a search of the PubMed database and references were examined from prior HPV natural history models and review papers. Study design and data quality from individual studies were compared and analyses meeting pre-defined criteria were selected.</p> <p>Results</p> <p>Published data meeting review eligibility criteria were most plentiful for natural history parameters relating to the progression and regression of cervical intraepithelial neoplasia (CIN) without HPV typing, and data concerning the natural history of HPV disease due to specific HPV types were often lacking. Epidemiologic evidence to support age-dependency in the risk of progression and regression of HPV disease was found to be weak, and an alternative hypothesis concerning the time-dependence of transition rates is explored. No data were found on the duration of immunity following HPV infection. In the area of clinical management, data were observed to be lacking on the proportion of clinically manifest anogenital warts that are treated and the proportion of cervical cancer cases that become symptomatic by stage.</p> <p>Conclusion</p> <p>Knowledge of the natural history of HPV disease has been considerably enhanced over the past two decades, through the publication of an increasing number of relevant studies. However, considerable opportunity remains for advancing our understanding of HPV natural history and the quality of associated models, particularly with respect to examining HPV age- and type-specific outcomes, and acquired immunity following infection.</p

Targeting human papillomavirus to reduce the burden of cervical, vulvar and vaginal cancer and pre-invasive neoplasia: establishing the baseline for surveillance.

Infection with high-risk human papillomavirus (HPV) is causally related to cervical, vulvar and vaginal pre-invasive neoplasias and cancers. Highly effective vaccines against HPV types 16/18 have been available since 2006, and are currently used in many countries in combination with cervical cancer screening to control the burden of cervical cancer. We estimated the overall and age-specific incidence rate (IR) of cervical, vulvar and vaginal cancer and pre-invasive neoplasia in Denmark, Iceland, Norway and Sweden in 2004-2006, prior to the availability of HPV vaccines, in order to establish a baseline for surveillance. We also estimated the population attributable fraction to determine roughly the expected effect of HPV16/18 vaccination on the incidence of these diseases

Model for Assessing Human Papillomavirus Vaccination Strategies

A prophylactic quadrivalent vaccine can cost-effectively reduce the incidence of cervical cancer, cervical intraepithelial neoplasia, and genital warts

Progression and regression of incident cervical HPV 6, 11, 16 and 18 infections in young women

<p>Abstract</p> <p>Background</p> <p>We describe type-specific progression, regression and persistence of incident human papillomavirus (HPV)-6-11-16 and -18 infections, along with type distribution in cervical intra-epithelial neoplasia (CIN) lesions.</p> <p>Methods</p> <p>The study population consisted of 16–23 year-old women undergoing Pap testing and cervical swab polymerase chain reaction testing for HPV DNA at approximate 6 month intervals for up to 4 years in the placebo arm of a clinical trial of an HPV 16-vaccine. HPV types in incident infections were correlated with types in lesion biopsy specimens.</p> <p>Results</p> <p>56.7% of CIN-1 and nearly one-third of CIN-2/3 lesions following incident HPV-6-11-16 or -18 infections did not correlate with the incident infection HPV type. Cumulative 36-month progression rates to CIN-2/3 testing positive for the relevant HPV type were highest for HPV-16 infections (16.5%), followed by HPV-18 (8.2%). Overall, 26.0% of CIN-1, 50.0% of CIN-2 and 70.6% of CIN-3 biopsies tested positive for HPV-6-11-16-18 infections.</p> <p>Conclusion</p> <p>Women with a given HPV type may often be co-infected or subsequently infected with other types which may lead to subsequent cervical lesions. This issue has been addressed in this study reporting data for the natural history of HPV-6-11-16 and -18 infections and is a relevant consideration in designing future studies to evaluate the incidence/risk of CIN following other type-specific HPV infections.</p

An Economic Overview of Chronic Obstructive Pulmonary Disease

Chronic obstructive pulmonary disease (COPD) is a major cause of mortality and morbidity. Relatively few pharmacoeconomic studies have been conducted on this disease. This article reviews available information about the utilisation of healthcare resources and cost of care, and the cost or cost effectiveness of therapeutic interventions reported for this disease. Burden-of-illness data indicate that hospital care, medications and oxygen therapy were the major cost drivers in these studies. Mean annual Medicare expenditures in the US were $US11 841 (2000 values) for patients with COPD compared with$US4901 for all covered patients. Utilisation was skewed; the most expensive 10% of the Medicare beneficiaries accounted for nearly 50% of total expenditures for this disease. Costs are associated with health status, age, physician specialty, geographic location and type of insurance coverage. Six types of interventions were assessed in the literature - pharmacotherapy, oxygen therapy, home care, surgery, exercise and rehabilitation and health education. The studies used different analytic strategies (e.g. cost-minimisation and cost-effectiveness analyses) and even within the realm of cost-effectiveness analyses, no uniformity existed as to how outcome was measured. Patient severity was not always delineated, and the length of the follow-up period, while quite short, varied. Only 11 of the 34 evaluations were based on randomised controlled trials. Cost-minimisation studies generally found no significant difference in the cost of antimicrobial treatment for first-line, second-line and third-line agents. Studies of bronchodilators indicated that ipratropium bromide alone or in combination with salbutamol (albuterol) was the preferred medication. The major area for achieving cost savings is by reducing hospital utilisation. As the annual rate of hospitalisation is relatively low, large patient samples will be required to demonstrate an economic advantage for a new therapy. The major challenges will be financing such a study, and selecting an outcome measure that satisfies both clinical and economic conventions.Antibacterials, Bronchodilators, Chronic obstructive pulmonary disease, Corticosteroids, Cost analysis, Pharmacoeconomics, Resource use, Surgery

Assessing the Annual Economic Burden of Preventing and Treating Anogenital Human Papillomavirus-Related Disease in the US: Analytic Framework and Review of the Literature

The anogenital human papillomavirus (HPV) is estimated to be the most commonly occurring sexually transmitted infection in the US. Comprehensive estimates of the annual economic burden associated with the prevention and treatment of anogenital HPV-related disease in the US population are currently unavailable. The purpose of this paper is to (i) outline an analytic framework from which to estimate the annual economic burden of preventing and treating anogenital HPV-related disease in the US; (ii) review available US literature concerning the annual economic burden of HPV; and (iii) highlight gaps in current knowledge where further study is particularly warranted. Among eight US studies identified that describe the annual economic burden pertaining to one or more aspects of anogenital HPV-related disease, three met the review eligibility criteria (published between 1990 and 2004, examined multiple facets of annual anogenital HPV-related economic burden, and clearly articulated the data and methods used in the estimation process). All costs were adjusted to 2004 $US. Estimates of the annual direct medical costs associated with cervical cancer were comparable across studies (range$US300-400 million). In contrast, there was a wide range across studies for estimates of the annual direct medical costs associated with cervical intraepithelial neoplasia (range $US700 million-$US2.3 billion). Only one study reported direct medical costs for anogenital warts ($US200 million) and routine cervical cancer screening ($US2.3 billion). No studies examined direct medical costs attributable to HPV-related anal, penile, vaginal or vulvar cancers, or the work and productivity losses resulting from time spent receiving medical care, morbidity or mortality. Current economic burden estimates would suggest annual direct medical costs associated with the prevention and treatment of anogenital warts and cervical HPV-related disease of at least $US4 billion. This figure would likely rise to at least$US5 billion per year if direct medical costs associated with other disease entities caused by the sexual transmission of HPV were included, with further additions to the economic burden totalling in the billions of dollars if work and productivity losses were incorporated, a research priority for future studies.Cervical-cancer, Cervical-intraepithelial-neoplasia, Cost-of-illness, Papilloma, Warts