Inefficiencies and High-Value Improvements in U.S. Cervical Cancer Screening Practice: A Cost-Effectiveness Analysis.

BACKGROUND: Studies suggest that cervical cancer screening practice in the United States is inefficient. The cost and health implications of nonadherence in the screening process compared with recommended guidelines are uncertain. OBJECTIVE: To estimate the benefits, costs, and cost-effectiveness of current cervical cancer screening practice and assess the value of screening improvements. DESIGN: Model-based cost-effectiveness analysis. DATA SOURCES: New Mexico HPV Pap Registry; medical literature. TARGET POPULATION: Cohort of women eligible for routine screening. TIME HORIZON: Lifetime. PERSPECTIVE: Societal. INTERVENTION: Current cervical cancer screening practice; improved adherence to guidelines-based screening interval, triage testing, diagnostic referrals, and precancer treatment referrals. OUTCOME MEASURES: Reductions in lifetime cervical cancer risk, quality-adjusted life-years (QALYs), lifetime costs, incremental cost-effectiveness ratios, and incremental net monetary benefits (INMBs). RESULTS OF BASE-CASE ANALYSIS: Current screening practice was associated with lower health benefit and was not cost-effective relative to guidelines-based strategies. Improvements in the screening process were associated with higher QALYs and small changes in costs. Perfect adherence to screening every 3 years with cytologic testing and adherence to colposcopy/biopsy referrals were associated with the highest INMBs ($759 and $741, respectively, at a willingness-to-pay threshold of $100,000 per QALY gained); together, the INMB increased to $1645. RESULTS OF SENSITIVITY ANALYSIS: Current screening practice was inefficient in 100% of simulations. The rank ordering of screening improvements according to INMBs was stable over a range of screening inputs and willingness-to-pay thresholds. LIMITATION: The effect of human papillomavirus vaccination was not considered. CONCLUSIONS: The added health benefit of improving adherence to guidelines, especially the 3-year interval for cytologic screening and diagnostic follow-up, may justify additional investments in interventions to improve U.S. cervical cancer screening practice. PRIMARY FUNDING SOURCE: U.S. National Cancer Institute.

Human papillomavirus testing 2007-2012: co-testing and triage utilization and impact on subsequent clinical management.

In the United States, high-risk human papillomavirus (HPV) testing is recommended for women with atypical squamous cells of unknown significance (ASC-US) cytology, and co-testing with cytology and HPV is a recommended option for screening women aged ≥ 30 years. No population-based data are available to examine utilization of HPV testing in the United States. Using the New Mexico HPV Pap Registry data resource, we describe population trends (2007-2012) in utilization and positivity rates for HPV testing as a routine co-testing screening procedure and for triage of ASC-US and other cytologic outcomes. For women aged 30-65 years co-testing increased from 5.2% in 2007 to 19.1% in 2012 (p < 0.001). Overall 82% of women with ASC-US cytology who did not receive co-testing also had an HPV test. HPV positivity was age and cytology result dependent but did not show time trends. For women with negative cytology, 64% received an additional screening test within 3 years if no co-test was done or if it was positive, but this was reduced to 47% with a negative co-test. Reflex HPV testing for ASC-US cytology is well established and occurs in most women. Evidence for reflex testing is also observed following other abnormal cytology outcomes. Co-testing in women aged 30-65 years has more than tripled from 2007 to 2012, but was still only used in 19.1% of women aged 30-65 years attending for screening in 2012. Women receiving co-testing had longer repeat screening intervals, but rescreening within 3 years is still very common even with co-testing.

No evidence for synergy between human papillomavirus genotypes for the risk of high-grade squamous intraepithelial lesions in a large population-based study.

BACKGROUND: Multiple human papillomavirus (HPV) genotypes may be independently or synergistically associated with risk of high-grade squamous intraepithelial lesions (HSILs). We evaluated the risk of HSIL in women concomitantly infected with multiple HPV genotypes. METHODS: A population-based stratified sample of 59 664 cervical cytology specimens from women residing in New Mexico were evaluated for cytologic abnormalities and HPV genotypes. We calculated the risk of HSIL in women infected with a single HPV genotype and the risk in those infected with multiple HPV genotypes. RESULTS: The highest risk of HSIL was observed for HPV-16 (0.036), followed by HPV-33 (0.028), HPV-58 (0.024), and HPV-18 (0.022). For most types, we observed a greater risk of HSIL in women infected with multiple carcinogenic HPV types. In contrast, the risk of HSIL was similar in women infected with HPV-16 and other types, compared with women infected with HPV-16 only. We observed an increased but plateauing risk of HSIL in women infected with multiple types, compared with those infected with a single type, with risk ratios of 1.5 (95% confidence interval [CI], 1.2-1.8), 1.7 (95% CI, 1.3-2.4), and 1.4 (95% CI, 0.83-2.5) for women infected with 2, 3, and ≥4 genotypes, respectively. CONCLUSIONS: In the largest population-based study of HPV genotypes and cytologic outcomes so far, we did not see more than additive effects of HPV types on the risk of HSIL in women infected with multiple types.

The influence of type-specific human papillomavirus infections on the detection of cervical precancer and cancer: A population-based study of opportunistic cervical screening in the United States.

There are limited data on the prospective risks of detecting cervical precancer and cancer in United States (US) populations specifically where the delivery of opportunistic cervical screening takes place outside managed care and in the absence of organized national programs. Such data will inform the management of women with positive screening results before and after widespread human papillomavirus (HPV) vaccination and establishes a baseline preceding recent changes in US cervical cancer screening guidelines. Using data reported to the statewide passive surveillance systems of the New Mexico HPV Pap Registry, we measured the 3-year HPV type-specific cumulative incidence of cervical intraepithelial neoplasia grade 2 or more severe (CIN2+) and grade 3 or more severe (CIN3+) detected during real-world health care delivery across a diversity of organizations, payers, clinical settings, providers and patients. A stratified sample of 47,541 cervical cytology specimens from a screening population of 379,000 women underwent HPV genotyping. Three-year risks for different combinations of cytologic interpretation and HPV risk group ranged from <1% (for several combinations) to approximately 70% for CIN2+ and 55% for CIN3+ in women with high-grade (HSIL) cytology and HPV16 infection. A substantial proportion of CIN2+ (35.7%) and CIN3+ (30.9%) were diagnosed following negative cytology, of which 62.3 and 78.2%, respectively, were high-risk HPV positive. HPV16 had the greatest 3-year risks (10.9% for CIN2+,8.0% for CIN3+) followed by HPV33, HPV31, and HPV18. Positive results for high-risk HPV, especially HPV16, the severity of cytologic interpretation, and age contribute independently to the risks of CIN2+ and CIN3+.

Concurrence of multiple human papillomavirus infections in a large US population-based cohort.

We examined the concurrence of multiple human papillomavirus (HPV) infections in 47,617 women who underwent cervical screening in New Mexico between December 2007 and April 2009 using the LINEAR ARRAY HPV Genotyping Test (Roche Diagnostics, Indianapolis, Indiana), which detects 37 different types of HPV. Our primary goal was to examine the distributions of multiple HPV types with a special interest in negative interactions, which could signal the possibility of type replacement associated with a common niche if some HPV types were prevented by vaccination. Multiple infections were found to be more common than expected under independence, but this could largely be accounted for by a woman-specific latent heterogeneity parameter which was found to be dependent on age and cytological grade. While multiple infections were more common in young women and in those with abnormal cytology, greater heterogeneity was seen in older women and in those with normal cytology, possibly reflecting greater variability in exposure due to current or past HPV exposure or due to heterogeneity in related HPV reactivation or in immune responses to HPV infection or persistence. A negative interaction was found between HPV 16 and several other HPV types for women with abnormal cytology but not for those with normal cytology, suggesting that type replacement in women vaccinated against HPV 16 is unlikely to be an issue for the general population.

Cervical excisional treatment of young women: a population-based study.

OBJECTIVE: Assessment of cytology and biopsy results preceding cervical excisional treatment and their association with excisional histology, to evaluate compliance with treatment recommendations and the potential effect of revisions in cervical histology terminology and usage. METHOD: Data from a unique statewide population-based screening registry was used to describe the use and histologic outcomes of cervical excisional procedures in the year following an abnormal cervical screening cytology. RESULTS: From 2007 to 2011, LEEP rates decreased 87%, 45%, and 16% for women aged 15-20, 21-24, and 25-29 years, respectively. Reductions were attributable to an overall decline in cervical screening and colposcopy, and a decrease in LEEP following a diagnosis of less than cervical intraepithelial neoplasia grade 2 (0.7) for women aged 30-39 years. Irrespective of age, CIN2 was the most common histologic antecedent of excisional treatment (42%), with most (80%) preceded by

A population-based study of human papillomavirus genotype prevalence in the United States: baseline measures prior to mass human papillomavirus vaccination.

Currently, two prophylactic human papillomavirus (HPV) vaccines targeting HPV 16 and 18 have been shown to be highly efficacious for preventing precursor lesions although the effectiveness of these vaccines in real-world clinical settings must still be determined. Toward this end, an ongoing statewide surveillance program was established in New Mexico to assess all aspects of cervical cancer preventive care. Given that the reduction in cervical cancer incidence is expected to take several decades to manifest, a systematic population-based measurement of HPV type-specific prevalence employing an age- and cytology-stratified sample of 47,617 women attending for cervical screening was conducted prior to widespread HPV vaccination. A well-validated polymerase chain reaction (PCR) method for 37 HPV genotypes was used to test liquid-based cytology specimens. The prevalence for any of the 37 HPV types was 27.3% overall with a maximum of 52% at age of 20 years followed by a rapid decline at older ages. The HPV 16 prevalences in women aged ≤ 20 years, 21-29 years or ≥ 30 years were 9.6, 6.5 and 1.8%, respectively. The combined prevalences of HPV 16 and 18 in these age groups were 12.0, 8.3 and 2.4%, respectively. HPV 16 and/or HPV 18 were detected in 54.5% of high-grade squamous intraepithelial (cytologic) lesions (HSIL) and in 25.0% of those with low-grade SIL (LSIL). These baseline data enable estimates of maximum HPV vaccine impact across time and provide critical reference measurements important to assessing clinical benefits and potential harms of HPV vaccination including increases in nonvaccine HPV types (i.e., type replacement).

Relationships of p16 Immunohistochemistry and Other Biomarkers With Diagnoses of Cervical Abnormalities: Implications for LAST Terminology.

CONTEXT.­: Lower Anogenital Squamous Terminology (LAST) standardization recommended p16INK4a immunohistochemistry (p16 IHC) for biopsies diagnosed morphologically as cervical intraepithelial neoplasia (CIN) grade 2 (CIN2) to classify them as low-grade or high-grade squamous intraepithelial lesions (HSILs). OBJECTIVE.­: To describe the relationships of p16 IHC and other biomarkers associated with cervical cancer risk with biopsy diagnoses. DESIGN.­: A statewide, stratified sample of cervical biopsies diagnosed by community pathologists (CPs), including 1512 CIN2, underwent a consensus, expert pathologist panel (EP) review (without p16 IHC results), p16 IHC interpretation by a third pathology group, and human papillomavirus (HPV) genotyping, results of which were grouped hierarchically according to cancer risk. Antecedent cytologic interpretations were also available. RESULTS.­: Biopsies were more likely to test p16 IHC positive with increasing severity of CP diagnoses, overall (Ptrend ≤ .001) and within each HPV risk group (Ptrend ≤ .001 except for low-risk HPV [Ptrend < .010]). All abnormal grades of CP-diagnosed biopsies were more likely to test p16 IHC positive with a higher HPV risk group (Ptrend < .001), and testing p16 IHC positive was associated with higher HPV risk group than testing p16 IHC negative for each grade of CP-diagnosed biopsies (P < .001). p16 IHC-positive, CP-diagnosed CIN2 biopsies were less likely than CP-diagnosed CIN3 biopsies to test HPV16 positive, have an antecedent HSIL+ cytology, or to be diagnosed as CIN3+ by the EP (P < .001 for all). p16 IHC-positive, CP-diagnosed CIN1 biopsies had lower HPV risk groups than p16 IHC-negative, CP-diagnosed CIN2 biopsies (P < .001). CONCLUSIONS.­: p16 IHC-positive, CP-diagnosed CIN2 appears to be lower cancer risk than CP-diagnosed CIN3. LAST classification of "HSIL" diagnosis, which includes p16 IHC-positive CIN2, should annotate the morphologic diagnosis (CIN2 or CIN3) to inform all management decisions, which is especially important for young (<30 years) women diagnosed with CIN2 for whom surveillance rather than treatment is recommended.

Anemia management and association of race with mortality and hospitalization in a large not-for-profit dialysis organization.

BACKGROUND: The optimal hemoglobin target and possible toxicity of epoetin therapy in hemodialysis patients are controversial. Previous studies suggest that African American patients use higher doses of epoetin and have better survival compared with white hemodialysis patients. STUDY DESIGN: Retrospective longitudinal cohort. SETTING & PARTICIPANTS: Epoetin-exposed incident hemodialysis patients (N = 12,733; African Americans, n = 4,801; white, n = 7,386) treated in Dialysis Clinic Inc facilities during 2000 to 2006. PREDICTORS: Hemoglobin, epoetin, iron. OUTCOMES: Mortality, hospitalization. MEASUREMENTS: Proportional hazards models with time-varying covariates. RESULTS: Hemoglobin concentrations less than 10 g/dL in whites and less than 11 g/dL in African Americans were associated with increased mortality and hospitalization versus the referent hemoglobin level of 11 to 11.9 g/dL. Hemoglobin levels of 13 g/dL or greater in whites were associated with decreased noncardiovascular mortality. Six-month cumulative epoetin doses of 20,000 U/wk or greater were associated with increased mortality and hospitalization versus the referent group (8,000 to 12,499 U/wk). Epoetin doses less than 8,000 U/wk were associated with decreased risk. Higher epoetin doses were associated with increased mortality at hemoglobin concentrations of 10 to 12.9 g/dL and with increased hospitalization at all hemoglobin concentrations of 10 g/dL or greater. Higher epoetin doses were associated with increased mortality and hospitalization within each tertile of serum albumin concentration. These patterns did not differ by race. LIMITATIONS: Treatment-by-indication bias and unidentified confounders cannot be excluded. Small sample sizes in the highest and lowest hemoglobin strata decrease statistical power. CONCLUSIONS: Relationships between hemoglobin concentration and mortality differed between African Americans and whites. Additionally, the relationship of lower mortality with greater achieved hemoglobin concentration seen in white patients was observed for all-cause, but not cardiovascular, mortality. A higher cumulative epoetin dose was associated with worse outcomes, even in patients with albumin levels greater than 4 g/dL. There were no statistically significant interactions between race and epoetin dose. Further studies are needed to confirm and to define the mechanism of these findings.

Role of HPV Genotype, Multiple Infections, and Viral Load on the Risk of High-Grade Cervical Neoplasia.

BACKGROUND: Human papillomavirus (HPV) testing provides a much more sensitive method of detection for high-grade lesions than cytology, but specificity is low. Here, we explore the extent to which full HPV genotyping, viral load, and multiplicity of types can be used to improve specificity. METHODS: A population-based sample of 47,120 women undergoing cervical screening was tested for 13 high-risk HPV genotypes. Positive predictive values (PPV) for cervical intraepithelial neoplasia (CIN) grade 2 or worse (CIN2+; N = 3,449) and CIN3 or worse (CIN3+; N = 1,475) over 3 years of follow-up were estimated for HPV genotype and viral load. Weighted multivariate logistic regression models were used to estimate the odds of CIN2+ or CIN3+ according to genotype, multiplicity of types, and viral load. RESULTS: High-risk HPV was detected in 15.4% of women. A hierarchy of HPV genotypes based on sequentially maximizing PPVs for CIN3+ found HPV16>33>31 to be the most predictive, followed sequentially by HPV18>35>58>45>52>59>51>39>56>68. After adjusting for higher ranked genotypes, the inclusion of multiple HPV infections added little to risk prediction. High viral loads for HPV18, 35, 52, and 58 carried more risk than low viral loads for HPV16, 31, and 33. High viral load for HPV16 was significantly more associated with CIN3+ than low viral load. CONCLUSIONS: HPV genotype and viral load, but not multiplicity of HPV infections, are important predictors of CIN2+ and CIN3+. IMPACT: The ability to identify women at higher risk of CIN2+ and CIN3+ based on both HPV genotype and viral load could be important for individualizing triage plans, particularly as HPV becomes the primary screening test.

Revised norms for the Lollipop Test for children ages 42 to 65 months.

Lollipop Test scores were acquired for 1,402 preschoolers in southwestern Indiana. Means and standard deviations for both boys and girls by 6-mo. intervals from the ages of 42 through 65 months showed scores increased significantly across ages, with girls scoring significantly higher than boys in all age groups. Current mean scores are similar to those published in 1988 for boys and slightly higher for girls.

Prostate cancer testing following a negative prostate biopsy: over testing the elderly.

BACKGROUND: Screening elderly men for prostate cancer is not recommended because definitive treatments are unlikely to extend life expectancy. OBJECTIVE: Describe clinical outcomes after a negative prostate biopsy in a population-based cohort of men ages 65 and older. DESIGN: Retrospective cohort study. PARTICIPANTS: 9,410 Medicare-eligible men who underwent a prostate biopsy in Los Angeles or New Mexico in 1992. MEASUREMENTS: We used Medicare and SEER databases to identify a cohort with an initial negative biopsy (n = 7,119) and to ascertain survival, subsequent PSA testing, prostate biopsies, and prostate cancer detection and treatment through 1997. RESULTS: The overall 5-year survival was 79.4% (95% CI 78.4-80.3), but only 74.6% (72.4-76.7) for men ages 75-79 at the time of the initial negative biopsy and 55.0% (51.9-57.9) for men ages 80+. During a median 4.5 years follow-up, a cumulative 75.0% (73.9-76.1) of the cohort underwent PSA testing. Among men ages 75-79 and 80+, the cumulative proportions that underwent PSA testing were 75.4% (73.0-77.8) and 74.3% (71.1-77.5), respectively. Additionally, 29.1% (26.7-31.6) of men ages 75-79 and 20.1% (17.6-23.1) of men ages 80+ underwent repeat prostate biopsy, and 10.9% (9.4-12.7) and 8.3% (6.6-10.4), respectively, were diagnosed with cancer. Among men ages 75+ with localized cancers, approximately 34% received definitive treatment. CONCLUSIONS: High proportions of men ages 75+ underwent PSA testing and repeat prostate biopsies after an initial negative prostate biopsy. Given the known harms and uncertain benefits for finding and treating localized cancer in elderly men, most continued PSA testing after a negative biopsy is potentially inappropriate.

Outcomes in Women With Cytology Showing Atypical Squamous Cells of Undetermined Significance With vs Without Human Papillomavirus Testing.

IMPORTANCE: Little is known about the long-term yield of high-grade cervical intraepithelial neoplasia (CIN) and the influence on biopsy and treatment rates of human papillomavirus (HPV) triage of cytology showing atypical squamous cells of undetermined significance (hereafter ASC-US cytology). OBJECTIVE: To examine 5-year outcomes after ASC-US cytology with vs without HPV testing. DESIGN, SETTING, AND PARTICIPANTS: In this observational study, all cervical cytology and HPV testing reports from January 1, 2007, to December 31, 2012, were obtained for women throughout New Mexico and linked to pathology reports. The dates of the analysis were May 4, 2015, to January 13, 2017. MAIN OUTCOMES AND MEASURES: Influence of HPV testing on disease yield, time to histologically confirmed disease, and biopsy or loop electrosurgical excision procedure rates. RESULTS: A total of 457 317 women (mean [SD] age, 39.8 [12.5] years) with a screening test were recorded between 2008 and 2012, and 20 677 (4.5%) of the first cytology results per woman were reported as ASC-US. CIN grade 3 or more severe (CIN3+) lesions were detected in 2.49% of women with HPV testing vs 2.15% of women without HPV testing (P = .23). Time to CIN3+ detection was much shorter in those with HPV testing vs those without testing (median, 103 vs 393 days; P < .001). CIN grade 1 was detected in 11.6% of women with HPV testing vs 6.6% without testing (relative risk, 1.76; 95% CI, 1.56-2.00; P < .001). Loop electrosurgical excision procedure rates within 5 years were 20.0% higher in those who underwent HPV testing, resulting in more CIN2+ and CIN3+ detection. CONCLUSIONS AND RELEVANCE: Human papillomavirus testing led to faster and more complete diagnosis of cervical disease, but 55.8% more biopsies and 20.0% more loop electrosurgical excision procedures were performed. In those tested, virtually all high-grade disease occurred in the 43.1% of women who were HPV positive, allowing clinical resources to be focused on women who need them most. These data provide essential information for cervical screening guidelines and public health policy.

Population-Based Incidence Rates of Cervical Intraepithelial Neoplasia in the Human Papillomavirus Vaccine Era.

IMPORTANCE: A substantial effect of human papillomavirus (HPV) vaccines on reducing HPV-related cervical disease is essential before modifying clinical practice guidelines in partially vaccinated populations. OBJECTIVE: To determine the population-based cervical intraepithelial neoplasia (CIN) trends when adjusting for changes in cervical screening practices that overlapped with HPV vaccination implementation. DESIGN, SETTING, AND PARTICIPANTS: The New Mexico HPV Pap Registry, which captures population-based estimates of both cervical screening prevalence and CIN, was used to compute CIN trends from January 1, 2007, to December 31, 2014. Under New Mexico Administrative Code, the New Mexico HPV Pap Registry, a statewide public health surveillance program, receives mandatory reporting of all cervical screening (cytologic and HPV testing) and any cervical, vulvar, and vaginal histopathological findings for all women residing in New Mexico irrespective of outcome. MAIN OUTCOME MEASURES: Prespecified outcome measures included low-grade CIN (grade 1 [CIN1]) and high-grade CIN (grade 2 [CIN2] and grade 3 [CIN3]). RESULTS: From 2007 to 2014, a total of 13 520 CIN1, 4296 CIN2, and 2823 CIN3 lesions were diagnosed among female individuals 15 to 29 years old. After adjustment for changes in cervical screening across the period, reductions in the CIN incidence per 100 000 women screened were significant for all grades of CIN among female individuals 15 to 19 years old, dropping from 3468.3 to 1590.6 for CIN1 (annual percentage change [APC], -9.0; 95% CI, -12.0 to -5.8; P < .001), from 896.4 to 414.9 for CIN2 (APC, -10.5; 95% CI, -18.8 to -1.2; P = .03), and from 240.2 to 0 for CIN3 (APC, -41.3; 95% CI, -65.7 to 0.3; P = .05). Reductions in the CIN2 incidence were also significant for women 20 to 24 years old, dropping from 1027.7 to 627.1 (APC, -6.3; 95% CI, -10.9 to -1.4; P = .02). CONCLUSIONS AND RELEVANCE: Population-level decreases in CIN among cohorts partially vaccinated for HPV may be considered when clinical practice guidelines for cervical cancer screening are reassessed. Evidence is rapidly growing to suggest that further increases in raising the age to start screening are imminent, one step toward integrating screening and vaccination.

Ethnic differences in the use of complementary and alternative therapies among adults with osteoarthritis.

INTRODUCTION: The use of complementary and alternative medicine (CAM) in the United States has been rising steadily, especially among people with chronic conditions such as osteoarthritis. It has been suggested that ethnicity and acculturation may influence use of CAM. The purpose of this study was to assess the influence of ethnicity and acculturation on patterns of CAM use among Hispanic and non-Hispanic white adults with osteoarthritis. METHODS: We conducted interviews in person, in English or Spanish, using a 255-item survey. We randomly selected participants aged 18 to 84 years from patients at university-based primary care outpatient clinics who had been diagnosed with osteoarthritis during the previous year. Measures included prevalence and types of CAM use, sociodemographic factors, self-reported ethnicity, and degree of acculturation according to language use. RESULTS: The Hispanic (n = 218) and non-Hispanic white (n = 204) populations showed similar rates of overall current CAM use (65.5% Hispanic vs 67.8% NHW) at time of interview. However, although more Hispanics used oral herbs (P = .03) and magnets or copper jewelry (P = .03), more non-Hispanic whites used nutritional supplements (P < .001). Hispanics speaking primarily English mirrored patterns of CAM use among non-Hispanic whites. These effects persisted after controlling for age, sex, income, education, degree of disability, and disease duration. CONCLUSION: In this population, ethnicity was a significant influence on patterns of CAM use but did not affect overall rates of use. Some differences were more pronounced among Spanish-speaking Hispanics, reflecting the incorporation of folk or traditional remedies into their health care practices.

Risk Stratification Using Human Papillomavirus Testing among Women with Equivocally Abnormal Cytology: Results from a State-Wide Surveillance Program.

BACKGROUND: Clinical guidelines for cervical cancer screening have incorporated comparative risks of cervical intraepithelial neoplasia grade 3 or cancer (CIN3(+)) for various screening outcomes to determine management. Few cohorts are large enough to distinguish CIN3(+) risks among women with minor abnormalities versus negative cytology because of low incidence. The New Mexico Human Papillomavirus (HPV) Pap Registry offers a unique opportunity to evaluate cervical cancer screening in a diverse population across a broad-spectrum of health service delivery. METHODS: Kaplan-Meier and logistic-Weibull survival models were used to estimate cumulative risks of CIN3(+) among women ages 21 to 64 who were screened in New Mexico between 2007 and 2011 with negative, equivocal or mildly abnormal cytology, that is, atypical squamous cells of undetermined significance (ASC-US; with or without HPV triage), or low-grade squamous intraepithelial lesions (LSIL). RESULTS: We identified 452,045 women meeting the selection criteria. The 3-year CIN3(+) risks for women with negative, ASC-US, and LSIL cytology were 0.30%, 2.6%, and 5.2%, respectively. HPV triage of ASC-US stratified 3-year CIN3(+) risks were 0.72% for HPV-negative and 7.7% for HPV-positive. Risks tended to decline after age 30 for all screening results. CONCLUSIONS: In this state-wide population-based cohort, cytology and HPV triage of ASC-US stratified women's CIN3(+) risk into similar patterns observed previously, suggesting the validity of screening guidelines for diverse populations in the United States. Absolute risk estimates should be compared across other large populations. IMPACT: Strategies for HPV triage of ASC-US derived from clinical trials are upheld in large clinical practice settings and across diverse screening populations in the United States.

Similar Risk Patterns After Cervical Screening in Two Large U.S. Populations: Implications for Clinical Guidelines.

OBJECTIVE: To compare the risks of histologic high-grade cervical intraepithelial neoplasia (CIN) or worse after different cervical cancer screening test results between two of the largest U.S. clinical practice research data sets. METHODS: The New Mexico Human Papillomavirus (HPV) Pap Registry is a statewide registry representing a diverse population experiencing varied clinical practice delivery. Kaiser Permanente Northern California is a large integrated health care delivery system practicing routine HPV cotesting since 2003. In this retrospective cohort study, a logistic-Weibull survival model was used to estimate and compare the cumulative 3- and 5-year risks of histologic CIN 3 or worse among women aged 21-64 years screened in 2007-2011 in the New Mexico HPV Pap Registry and 2003-2013 in Kaiser Permanente Northern California. Results were stratified by age and baseline screening result: negative cytology, atypical squamous cells of undetermined significance (ASC-US) (with or without HPV triage), low-grade squamous intraepithelial lesion, and high-grade squamous intraepithelial lesion. RESULTS: There were 453,618 women in the New Mexico HPV Pap Registry and 1,307,528 women at Kaiser Permanente Northern California. The 5-year CIN 3 or worse risks were similar within screening results across populations: cytology negative (0.52% and 0.30%, respectively, P<.001), HPV-negative and ASC-US (0.72% and 0.49%, respectively, P=.5), ASC-US (3.4% and 3.4%, respectively, P=.8), HPV-positive and ASC-US (7.7% and 7.1%, respectively, P=.3), low-grade squamous intraepithelial lesion (6.5% and 5.4%, respectively, P=.009), and high-grade squamous intraepithelial lesion (53.1% and 50.4%, respectively, P=.2). Cervical intraepithelial neoplasia grade 2 or worse risks and 3-year risks had similar trends across populations. Age-stratified analyses showed more variability, especially among women aged younger than 30 years, but patterns of risk stratification were comparable. CONCLUSION: Current U.S. cervical screening and management recommendations are based on comparative risks of histologic high-grade CIN after screening test results. The similar results from these two large cohorts from different real-life clinical practice settings support risk-based management thresholds across U.S. clinical populations and practice settings.

Human papillomavirus genotype-specific prevalence across the continuum of cervical neoplasia and cancer.

BACKGROUND: The New Mexico HPV Pap Registry was established to measure the impact of cervical cancer prevention strategies in the United States. Before widespread human papillomavirus (HPV) vaccine implementation, we established the baseline prevalence for a broad spectrum of HPV genotypes across the continuum of cervical intraepithelial neoplasia (CIN) and cancer. METHODS: A population-based sample of 6,272 tissue specimens was tested for 37 HPV genotypes. The number of specimens tested within each diagnostic category was: 541 negative, 1,411 CIN grade 1 (CIN1), 2,226 CIN grade 2 (CIN2), and 2,094 CIN grade 3 (CIN3) or greater. Age-specific HPV prevalence was estimated within categories for HPV genotypes targeted by HPV vaccines. RESULTS: The combined prevalence of HPV genotypes included in the quadrivalent and nonavalent vaccines increased from 15.3% and 29.3% in CIN1 to 58.4% and 83.7% in CIN3, respectively. Prevalence of HPV types included in both vaccines tended to decrease with increasing age for CIN1, CIN2, CIN3, and squamous cell carcinoma (SCC), most notably for CIN3 and SCC. The six most common HPV types in descending order of prevalence were HPV-16, -31, -52, -58, -33, and -39 for CIN3 and HPV-16, -18, -31, -45, -52, and -33 for invasive cancers. CONCLUSIONS: Health economic modeling of HPV vaccine impact should consider age-specific differences in HPV prevalence. IMPACT: Population-based HPV prevalence in CIN is not well described, but is requisite for longitudinal assessment of vaccine impact and to understand the effectiveness and performance of various cervical screening strategies in vaccinated and unvaccinated women.

The Interpretive Variability of Cervical Biopsies and Its Relationship to HPV Status.

Diagnostic interpretation of a cervical biopsy is a key element in the decision to treat or not to treat a woman with an abnormal screening test. This study assesses the variability of these diagnostic interpretations on a population basis using the New Mexico HPV Pap Registry database. An experienced panel of gynecologic pathologists reviewed a stratified random sample of 6272 biopsies, which was then extrapolated to the entire population of 21,297 biopsies read by the community pathologists. Diagnoses by the community and panel pathologists were compared, and paired diagnoses were correlated with positivity for human papillomavirus 16 (HPV16) and any high-risk HPV as objective measures of progressive potential. Panel agreement with the community diagnosis was 38.2% for cervical intraepithelial neoplasia grade 1 (CIN1), 38.0% for CIN grade 2 (CIN2), 68.0% for CIN grade 3 (CIN3), and 70.6% for cancer. The κ value was 0.46 overall but higher for dichotomous categorization based on CIN2 or CIN3 cutoff points (0.68 and 0.67, respectively). On a population basis, there were fewer CIN1 and more negative diagnoses in the panel review but similar proportions of CIN2 and CIN3. HPV16 and high-risk HPV positivity increased with disease severity, but panel review did not improve the correlation of higher-grade disease with these objective measures. In this population-based study of the variability in cervical diagnoses, we noted significant variability in the community and panel diagnoses, especially for CIN2, the threshold for excisional treatment. New biomarkers are needed to more accurately stratify precursor lesions according to their malignant potential.

Changes in nonmelanoma skin cancer incidence between 1977-1978 and 1998-1999 in Northcentral New Mexico.

Nonmelanoma skin cancer (NMSC) is a highly common form of malignant disease in light-skinned populations. In 1977-1978, the National Cancer Institute sponsored a population-based skin cancer survey that found marked geographic variability in the incidence of NMSC within the United States. Some of the highest rates were observed in the southwestern state of New Mexico within its non-Hispanic white population. We recently undertook a follow-up survey of NMSC in New Mexico and report here incidence rate data for non-Hispanic white residents of a three-county area in northcentral New Mexico for two 12-month time periods: June 1, 1977 to May 31, 1978 and July 1, 1998 to June 31, 1999. Our results show that incidence rates of basal cell carcinoma increased by 50% in males and 20% in females, whereas rates of squamous cell carcinoma roughly doubled in both males and females. Temporal analysis of rates according to major anatomical site showed the head and neck was consistently the most frequent site of occurrence, however, the greatest percentage increase in rates over time occurred at the upper and lower limbs. These findings are consistent with those reported for various other populations showing the incidence of NMSC has measurably increased since the 1970s.