Absolute risks of cervical precancer among women who fulfill exiting guidelines based on HPV and cytology cotesting.
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ABSTRACT:
SUBMITTER: Landy R
PROVIDER: S-EPMC6742586 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundThe main goal of cervical screening programs is to detect and treat precancer before cancer develops. Human papillomavirus (HPV) testing is more sensitive than cytology for detecting precancer. However, reports of rare HPV-negative, cytology-positive cancers are motivating continued use of both tests (cotesting) despite increased testing costs.MethodsWe quantified the detection of cervical precancer and cancer by cotesting compared with HPV testing alone at Kaiser Permanente Northern California (KPNC), where 1?208?710 women age 30?years and older have undergone triennial cervical cotesting since 2003. Screening histories preceding cervical cancers (n?=?623) and precancers (n?=?5369) were examined to assess the relative contribution of the cytology and HPV test components in identifying cases. The performances of HPV testing and cytology were compared using contingency table methods, general estimating equation models, and nonparametric statistics; all statistical tests were two-sided.ResultsHPV testing identified more women subsequently diagnosed with cancer (P < .001) and precancer (P < .001) than cytology. HPV testing was statistically significantly more likely to be positive for cancer at any time point (P < .001), except within 12?months (P = .10). HPV-negative/cytology-positive results preceded only small fractions of cases of precancer (3.5%) and cancer (5.9%); these cancers were more likely to be regional or distant stage with squamous histopathology than other cases. Given the rarity of cancers among screened women, the contribution of cytology to screening translated to earlier detection of at most five cases per million women per year. Two-thirds (67.9%) of women found to have cancer during 10?years of follow-up at KPNC were detected by the first cotest performed.ConclusionsThe added sensitivity of cotesting vs HPV alone for detection of treatable cancer affected extremely few women.
| S-EPMC6279277 | biostudies-literature
Project description:ObjectiveTo evaluate the adoption of HPV testing and recommended extended cervical cancer screening intervals in clinical practice, we described yearly uptake of Pap/HPV cotesting and estimated length of time between normal screens by patient characteristics.MethodsWe examined 55,575 Pap/HPV records from 27,035 women aged 30-65 years from the Johns Hopkins Hospital Pathology Data System between 2006 and 2013. Cotest uptake and median times to next screening test for cotests and cytology only were calculated. Adjusted hazard ratios were estimated using Cox proportional hazards models, with random effects adjustment for clustering within clinic.ResultsCotest usage increased from < 10% in 2006 to 78% in 2013. The median time to next screening test following normal cytology alone remained constant around 1.5 years. Screening intervals following a dual-negative cotest increased from 1.5 years in 2006/2007 to 2.5 years in 2010, coincident with increases in the proportion of women cotested. Intervals following a dual negative cotest were longer among Medicare patients (3 years) compared with privately insured women (2.5 years), and shorter among black (2 years) compared with white women (2.8 years).ConclusionBy mid-2013 we observed broad adoption of Pap/HPV cotesting in routine screening in a large academic medical center. Increased screening intervals were observed only among cotested women, while those screened by cytology alone continued to be screened almost annually. The influence of different combinations of race and insurance on screening intervals should be further evaluated to ensure balance of screening risks and benefits in the U.S.Population
| S-EPMC5754229 | biostudies-literature
Project description:ContextUS cervical cancer screening guidelines for human immunodeficiency virus (HIV)-uninfected women 30 years or older have recently been revised, increasing the suggested interval between Papanicolaou (Pap) tests from 3 years to 5 years among those with normal cervical cytology (Pap test) results who test negative for oncogenic human papillomavirus (HPV). Whether a 3-year or 5-year screening interval could be used in HIV-infected women who are cytologically normal and oncogenic HPV-negative is unknown.ObjectiveTo determine the risk of cervical precancer or cancer defined cytologically (high-grade squamous intraepithelial lesions or greater [HSIL+]) or histologically (cervical intraepithelial neoplasia 2 or greater [CIN-2+]), as 2 separate end points, in HIV-infected women and HIV-uninfected women who at baseline had a normal Pap test result and were negative for oncogenic HPV.Design, setting, and participantsParticipants included 420 HIV-infected women and 279 HIV-uninfected women with normal cervical cytology at their enrollment in a multi-institutional US cohort of the Women's Interagency HIV Study, between October 1, 2001, and September 30, 2002, with follow-up through April 30, 2011. Semiannual visits at 6 clinical sites included Pap testing and, if indicated, cervical biopsy. Cervicovaginal lavage specimens from enrollment were tested for HPV DNA using polymerase chain reaction. The primary analysis was truncated at 5 years of follow-up.Main outcome measureFive-year cumulative incidence of cervical precancer and cancer.ResultsNo oncogenic HPV was detected in 369 (88% [95% CI, 84%-91%]) HIV-infected women and 255 (91% [95% CI, 88%-94%]) HIV-uninfected women with normal cervical cytology at enrollment. Among these oncogenic HPV-negative women, 2 cases of HSIL+ were observed; an HIV-uninfected woman and an HIV-infected woman with a CD4 cell count of 500 cells/μL or greater. Histologic data were obtained from 4 of the 6 clinical sites. There were 6 cases of CIN-2+ in 145 HIV-uninfected women (cumulative incidence, 5% [95% CI, 1%-8%]) and 9 cases in 219 HIV-infected women (cumulative incidence, 5% [95% CI, 2%-8%]). This included 1 case of CIN-2+ in 44 oncogenic HPV-negative HIV-infected women with CD4 cell count less than 350 cells/μL (cumulative incidence, 2% [95% CI, 0%-7%]), 1 case in 47 women with CD4 cell count of 350 to 499 cells/μL (cumulative incidence, 2% [95% CI, 0%-7%]), and 7 cases in 128 women with CD4 cell count of 500 cells/μL or greater (cumulative incidence, 6% [95% CI, 2%-10%]). One HIV-infected and 1 HIV-uninfected woman had CIN-3, but none had cancer.ConclusionThe 5-year cumulative incidence of HSIL+ and CIN-2+ was similar in HIV-infected women and HIV-uninfected women who were cytologically normal and oncogenic HPV-negative at enrollment.
| S-EPMC3556987 | biostudies-literature
Project description:OBJECTIVE:In 2012, the US Preventive Services Task Force (USPSTF) and a consensus of 25 organizations endorsed concurrent cytology and human papillomavirus (HPV) testing ("cotesting") for cervical cancer screening. Past screening and management guidelines were implicitly based on risks defined by Pap-alone, without consideration of HPV test results. To promote management that is consistent with accepted practice, new guidelines incorporating cotesting should aim to achieve equal management of women at equal risk of cervical intraepithelial neoplasia grade 3 and cancer (CIN 3+). METHODS:We estimated cumulative 5-year risks of CIN 3+ for 965,360 women aged 30 to 64 years undergoing cotesting at Kaiser Permanente Northern California over 2003 to 2010. We calculated the implicit risk thresholds for Pap-alone and applied them for new management guidance on HPV and Pap cotesting, citing 2 examples: HPV-positive/atypical squamous cells of undetermined significance (ASC-US) and HPV-negative/Pap-negative. We call this guidance process "benchmarking." RESULTS:A low-grade squamous intraepithelial lesion result, for which immediate colposcopy is prescribed, carries a 5-year CIN 3+ risk of 5.2%, suggesting that test results with similar risks should be managed with colposcopy. Similarly, ASC-US (2.6% risk) is managed with a 6- to 12-month follow-up visit and Pap-negative (0.26% risk) is managed with a 3-year follow-up visit. The 5-year CIN 3+ risk for women with HPV-positive/ASC-US was 6.8% (95% confidence interval = 6.2%-7.6%). This is greater than the 5.2% risk implicitly leading to referral to colposcopy, consistent with current management recommendations that HPV-positive/ASC-US should be referred for immediate colposcopy. The 5-year CIN 3+ risk for women with HPV-negative/Pap-negative was 0.08% (95% confidence interval = 0.07%-0.09%), far below the 0.26% implicitly required for a 3-year return and justifying a longer (e.g., 5-year) return. CONCLUSIONS:Using the principle of "equal management of equal risks," benchmarking to implicit risk thresholds based on Pap-alone can be used to achieve safe and consistent incorporation of cotesting.
| S-EPMC3616419 | biostudies-literature
Project description:BackgroundIn 2012, updated cervical cancer screening recommendations were released with consensus on Papanicolaou (Pap) testing every 3 years for women age 21-65 years or Pap-human papillomavirus (HPV) cotesting at 5-year intervals for women age 30-65 years. Primary study aims: Assess current use of Pap-HPV cotesting and describe local population trends over time in Pap and Pap-HPV cotesting. Secondary aim: Assess sociodemographic factors correlating with screening.MethodsWe assessed Rochester Epidemiology Project data for Pap and Pap-HPV cotesting among women age 16 years and older living in Olmsted County, Minnesota, yearly from 2005 (study population n?=?47,203) through 2016 (study population n?=?49,510). We calculated 3-year (Pap) and 5-year (Pap-HPV) moving prevalence rates of screening as proportion of eligible population. Multivariable logistic regression was used to assess factors potentially associated with screening.ResultsIn 2016, 64.6% of 27,418 eligible 30- to 65-year-old women were up to date with cervical cancer screening; 60.8% had received Pap-HPV cotest screening. Significant declines in Pap completion rates over time were observed in all age groups, including an unexpected decline in 21- to 29-year-old women. Coincident with decreasing Pap screening rates, Pap-HPV cotesting significantly increased among women age 30-65 years, from 10.0% in 2007 to 60.8% in 2016.ConclusionsThis suggests increasing adoption of 2012 screening recommendations in the 30- to 65-year-old population. However, decline in Pap screening among 21- to 29-year-old women is concerning. Disparities by race, ethnicity, smoking status, and comorbidity level were observed. Results suggest need for multilevel patient and clinician interventions to increase cervical cancer screening adherence.
| S-EPMC6390646 | biostudies-literature
Project description:BackgroundHuman papillomavirus (HPV)-based screening programs still use one-size-fits-all protocols but efficiency and efficacy of programs may be improved by stratifying women based on previous screening results.Methods and findingsWe studied the association between cervical intraepithelial neoplasia grade 3 or cancer (CIN3+) and previous screening results in the Population-Based Screening Study Amsterdam (POBASCAM) trial, performed in the Netherlands in the setting of regular screening, where women aged from 29 to 61 years old were invited to cytology and HPV co-testing at enrolment in year 1999/2002 and at the next round in 2003/2007. We selected 18,448 women (9,293 from the intervention group and 9,155 from the control group) who tested HPV-negative in 2003/2007 and did not have cervical intraepithelial neoplasia grade 2 or worse (CIN2+) or hysterectomy after enrolment. Follow-up was collected until 14 years after the 2003/2007 screen, covering 4 rounds of screening. Risk of CIN3+ and CIN2+ among women with an HPV-negative test, irrespective of previous round results and stratified according to previous round HPV and cytology results, were calculated by the Kaplan-Meier method. During 14 years of follow-up, 62 CIN3+ cases (24 in the intervention group and 38 in the control group) were detected. HPV-negative women had a 14-year CIN3+ risk of 0.48% (95% confidence interval 0.37 to 0.62) and CIN2+ risk of 1.17% (0.99 to 1.38). The CIN3+ risk among HPV-negative women was increased in women with a previous positive HPV test (2.36%, 1.20 to 4.63; p < 0.001) or co-test (1.68%, 0.87 to 3.20; p < 0.001) and, equivalently, decreased in women with a previous negative HPV test (0.43%, 0.33 to 0.57) or a negative co-test (0.43%, 0.33 to 0.57). The CIN3+ risk was not influenced by the previous cytology result. The CIN3+ risk among HPV-negative women was increased after both a previous HPV16-positive test (3.90%, 1.47 to 10.12; p < 0.001) and a previous HPV16-negative/HPVother-positive test (1.91%, 0.76 to 4.74; p = 0.002). For endpoint CIN2+ (147 cases), findings were similar except that the CIN2+ risk was increased after previous abnormal cytology (4.06%, 2.30 to 7.12; p < 0.001). The presented risk estimates were calculated by tracking histological results through the Dutch nationwide pathology archive (PALGA) and were not adjusted for non-compliance with the colposcopy referral advice.ConclusionsHPV-negative women had an increased long-term risk of CIN3+ when the HPV test in the previous screening round was positive. This supports the implementation of risk-based intervals that depend on HPV results in the current and previous screening round.Trial registrationPOBASCAM trial, trial registration number ISRCTN20781131.
| S-EPMC9616214 | biostudies-literature
Project description: Not available
| S-EPMC4834967 | biostudies-literature
Project description:Background: Human Papilloma Virus has been considered as the main cause for cervical cancer. In this study we investigated epigenetic changes and especially methylation of specific sites of HPV genome. The main goal was to correlate methylation status with histological grade as well as to determine its accuracy in predicting the disease severity by establishing optimum methylation cutoffs. Methods: In total, sections from 145 cases genotyped as HPV16 were obtained from formalin- fixed, paraffin-embedded tissue of cervical biopsies, conization or hysterectomy specimens. Highly accurate pyrosequencing of bisulfite converted DNA, was used to quantify the methylation percentages of UTR promoter, enhancer and 5' UTR, E6 CpGs 494, 502, 506 and E7 CpGs 765, 780, 790. The samples were separated in different groupings based on the histological outcome. Statistical analysis was performed by SAS 9.4 for Windows and methylation cutoffs were identified by MATLAB programming language. Results: The most important methylation sites were at the enhancer and especially UTR 7535 and 7553 sites. Specifically for CIN3+ (i.e. HSIL or SCC) discrimination, a balanced sensitivity vs. specificity (68.1%, 66.2% respectively) with positive predictive value (PPV) and negative predictive value (NPV) (66.2%, 68.2% respectively) was achieved for UTR 7535 methylation of 6.1% cutoff with overall accuracy 67.1%, while for UTR 7553 a sensitivity 60.9%, specificity 69.0%, PPV=65.6%, NPV=64.5% and overall accuracy=65.0% at threshold 10.1% was observed. Conclusion: Viral HPV16 genome was found methylated in NF-1 binding sites of UTR in cases with high grade disease. Methylation percentages of E6 and E7 CpG sites were elevated at the cancer group.
| S-EPMC6746133 | biostudies-literature
Project description:OBJECTIVES:To assess the clinical and cost-effectiveness of human papillomavirus (HPV) primary screening triage with p16/Ki-67 dual stain cytology compared to cytology. METHODS:We conducted an Excel®-based budget impact model to estimate the preinvasive and invasive cervical cancer cases identified, mortality rate, direct medical costs, quality-adjusted life years (QALYs) and the incremental cost-effectiveness analysis of two strategies from the healthcare payer perspective. The study population is a cohort of women 30-65 years of age presenting for cervical screening. RESULTS:HPV primary screening triage with p16/Ki-67 dual stain showed higher sensitivity without losing specificity compared to conventional Pap smear. The improving the screening performance leads to decrease the prevalence of precancerous lesion, annual incidence and mortality of cervical cancer. The incidence of cervical cancer case detected by new algorithm compared with conventional method were 31,607 and 38,927, respectively. In addition, the new algorithm was more effective and more costly (average QALY 24.03, annual cost $13,262,693) than conventional cytology (average QALY 23.98, annual cost $7,713,251). The incremental cost-effective ratio (ICER) per QALY gained was $1,395. The sensitivity analysis showed if the cost of cytology and HPV test increased three times, the ICER would fall to $303/QALY gained and increased to $4,970/QALY gained, respectively. CONCLUSION:Our model results suggest that screening by use of HPV genotyping test as a primary screening test combined with dual stain cytology as the triage of HPV positive women in Thai population 30-65 years old is expected to be more cost-effective than conventional Pap cytology.
| S-EPMC6393632 | biostudies-literature
Project description:Although cervical cancer is an AIDS-defining condition, infection with human immunodeficiency virus (HIV) may only modestly increase the risk of cervical cancer. There is a paucity of information regarding factors that influence the natural history of human papillomavirus (HPV) in HIV-infected women. We examined factors associated with cervical intraepithelial neoplasia grade 3 or cancer (CIN3+) in Rwandan women infected with both HIV and HPV (HIV+/HPV+).In 2005, 710 HIV+ Rwandan women ?25 years enrolled in an observational cohort study; 476 (67%) tested HPV+. Each woman provided sociodemographic data, CD4 count, a cervical cytology specimen and cervicovaginal lavage (CVL), which was tested for >40 HPV genotypes by MY09/MY11 PCR assay. Logistic regression models calculated odds ratios (OR) and 95% confidence intervals (CI) of associations of potential risk factors for CIN3+ among HIV+/HPV+ women.Of the 476 HIV+/HPV+ women 42 (8.8%) were diagnosed with CIN3+. Factors associated with CIN3+ included ?7 (vs. 0-2) pregnancies, malarial infection in the previous six months (vs. never), and ?7 (vs. 0-2) lifetime sexual partners. Compared to women infected by non-HPV16 carcinogenic HPV genotypes, HPV16 infection was positively associated and non-carcinogenic HPV infection was inversely associated with CIN3+. CD4 count was significantly associated with CIN3+ only in analyses of women with non-HPV16 carcinogenic HPV (OR = 0.62 per 100 cells/mm(3), CI = 0.40-0.97).In this HIV+/HPV+ population, lower CD4 was significantly associated with CIN3+ only in women infected with carcinogenic non-HPV16. We found a trend for higher risk of CIN3+ in HIV+ women reporting recent malarial infection; this association should be investigated in a larger group of HIV+/HPV+ women.
| S-EPMC2958122 | biostudies-literature