The Potential Clinical and Economic Value of a Human Papillomavirus Primary Screening Test That Additionally Identifies Genotypes 31, 45, 51, and 52 Individually.

BACKGROUND: Although current human papillomavirus (HPV) genotype screening tests identify genotypes 16 and 18 and do not specifically identify other high-risk types, a new extended genotyping test identifies additional individual (31, 45, 51, and 52) and groups (33/58, 35/39/68, and 56/59/66) of high-risk genotypes. METHODS: We developed a Markov model of the HPV disease course and evaluated the clinical and economic value of HPV primary screening with Onclarity (BD Diagnostics, Franklin Lakes, NJ) capable of extended genotyping in a cohort of women 30 years or older. Women with certain genotypes were later rescreened instead of undergoing immediate colposcopy and varied which genotypes were rescreened, disease progression rate, and test cost. RESULTS: Assuming 100% compliance with screening, HPV primary screening using current tests resulted in 25,194 invasive procedures and 48 invasive cervical cancer (ICC) cases per 100,000 women. Screening with extended genotyping (100% compliance) and later rescreening women with certain genotypes averted 903 to 3163 invasive procedures and resulted in 0 to 3 more ICC cases compared with current HPV primary screening tests. Extended genotyping was cost-effective ($2298-$7236/quality-adjusted life year) when costing $75 and cost saving (median, $0.3-$1.0 million) when costing $43. When the probabilities of disease progression increased (2-4 times), extended genotyping was not cost-effective because it resulted in more ICC cases and accrued fewer quality-adjusted life years. CONCLUSIONS: Our study identified the conditions under which extended genotyping was cost-effective and even cost saving compared with current tests. A key driver of cost-effectiveness is the risk of disease progression, which emphasizes the need to better understand such risks in different populations.

Human Papillomavirus Same Genotype Persistence and Risk: A Systematic Review.

OBJECTIVE: The aim of the study was to examine whether high-grade cervical intraepithelial neoplasia (CIN) was more closely associated with human papillomavirus (HPV) same-genotype persistence (SGTP) versus clearance of prior infection with a subsequent infection by a new genotype (genotype switch [GS]), clearance of HPV infection, or acquisition of a new HPV infection after a negative infection status, during a follow-up testing subsequent to abnormal screening results. MATERIALS AND METHODS: MEDLINE, Cochrane Library, Health Technology Assessment, and clinicaltrials.gov were searched from January 2000 to July 2019 for prospective controlled trials and observational studies of women and retrospective studies using HPV assays with extended- or full-genotype reporting. The primary outcome was high-grade CIN after at least 2 rounds of testing. Overall quality of evidence for the risk estimate outcomes was assessed. Of the 830 identified abstracts, 66 full-text articles were reviewed, and 7 studies were included in the synthesis. The study protocol was registered with the PROSPERO International Prospective Register of Systematic Reviews (CRD42018091093). RESULTS: Continued HPV-positive women falls in 2 equally large groups: SGTP and GS. Sensitivity, positive predictive value, and positive likelihood ratio of SGTP were significantly higher than for GS. Human papillomavirus genotypes may be ranked into 3 tiers (immediate colposcopy, follow-up testing, return to routine screening), according to associated risk of persistence for high-grade CIN and to prevailing clinical action thresholds. CONCLUSIONS: There is moderately high-quality evidence to support the clinical utility of SGTP to improve risk discrimination for high-grade CIN compared with qualitative HPV testing without genotype-specific information.

GRADE guidelines: 15. Going from evidence to recommendation-determinants of a recommendation's direction and strength.

In the GRADE approach, the strength of a recommendation reflects the extent to which we can be confident that the composite desirable effects of a management strategy outweigh the composite undesirable effects. This article addresses GRADE's approach to determining the direction and strength of a recommendation. The GRADE describes the balance of desirable and undesirable outcomes of interest among alternative management strategies depending on four domains, namely estimates of effect for desirable and undesirable outcomes of interest, confidence in the estimates of effect, estimates of values and preferences, and resource use. Ultimately, guideline panels must use judgment in integrating these factors to make a strong or weak recommendation for or against an intervention.

Closing the quality gap: revisiting the state of the science (vol. 3: quality improvement interventions to address health disparities).

OBJECTIVE: This review evaluates the effectiveness of quality improvement (QI) strategies in reducing disparities in health and health care. DATA SOURCES: We identified papers published in English between 1983 and 2011 from the MEDLINE® database, the Cumulative Index of Nursing and Allied Health Literature (CINAHL), Web of Science Social Science Index, and PsycINFO. REVIEW METHODS: All abstracts and full-text articles were dually reviewed. Studies were eligible if they reported data on effectiveness of QI interventions on processes or health outcomes in the United States such that the impact on a health disparity could be measured. The review focused on the following clinical conditions: breast cancer, colorectal cancer, diabetes, heart failure, hypertension, coronary artery disease, asthma, major depressive disorder, cystic fibrosis, pneumonia, pregnancy, and end-stage renal disease. It assessed health disparities associated with race or ethnicity, socioeconomic status, insurance status, sexual orientation, health literacy/numeracy, and language barrier. We evaluated the risk of bias of individual studies and the overall strength of the body of evidence based on risk of bias, consistency, directness, and precision. RESULTS: Nineteen papers, representing 14 primary research studies, met criteria for inclusion. All but one of the studies incorporated multiple components into their QI approach. Patient education was part of most interventions (12 of 14), although the specific approach differed substantially across the studies. Ten of the studies incorporated self-management; this would include, for example, teaching individuals with diabetes to check their blood sugar regularly. Most (8 of 14) included some sort of provider education, which may have focused on the clinical issue or on raising awareness about disparities affecting the target population. Studies evaluated the effect of these strategies on disparities in the prevention or treatment of breast or colorectal cancer, cardiovascular disease, depression, or diabetes. Overall, QI interventions were not shown to reduce disparities. Most studies have focused on racial or ethnic disparities, with some targeted interventions demonstrating greater effect in racial minorities--specifically, supporting individuals in tracking their blood pressure at home to reduce blood pressure and collaborative care to improve depression care. In one study, the effect of a language-concordant breast cancer screening intervention was helpful in promoting mammography in Spanish-speaking women. For some depression care outcomes, the collaborative care model was more effective in less-educated individuals than in those with more education and in women than in men. CONCLUSIONS: The literature on QI interventions generally and their ability to improve health and health care is large. Whether those interventions are effective at reducing disparities remains unclear. This report should not be construed to assess the general effectiveness of QI in the health care setting; rather, QI has not been shown specifically to reduce known disparities in health care or health outcomes. In a few instances, some increased effect is seen in disadvantaged populations; these studies should be replicated and the interventions studied further as having potential to address disparities.