Dataset Information

Three-year risk of cervical precancer and cancer after the detection of low-risk human papillomavirus genotypes targeted by a commercial test.

ABSTRACT: To investigate the risk of cervical precancer and cancer associated with detection of human papillomavirus (HPV) 6, 11, and 42.We used data from the New Mexico Human Papillomavirus Pap Registry. A stratified sample of 59,644 residual cervical cytology specimens from a population of 379,000 underwent HPV genotyping. We measured the 3-year cumulative incidence of cervical intraepithelial neoplasia grade 2 or more severe (CIN 2+) and grade 3 or more severe (CIN 3+) after detection of single HPV 6, 11, or 42 infections or single or multiple infections of HPV 6, 11, or 42 ("HPV 6, 11, 42, or combinations"; n=581).The overall prevalence of a single infection of HPV 6, 11, or 42 was 0.8% (95% confidence interval [CI] 0.7-0.9%). The 3-year risks of CIN 2+ and CIN 3+ after HPV 6, 11, 42, or combinations infections (n=581) were 0.4% (CI 0.1-0.7%) for CIN 2+ and 0.0% for CIN 3+ (nota bene, no CI was calculable because no events occurred), respectively. By comparison, the 3-year risks of CIN 2+ and CIN 3+ after a negative HPV result (n=27,522) were 0.2% (95% CI 0.1-0.2%) and 0.1% (95% CI 0.0-0.1%), respectively.Detection of HPV 6, 11, 42, or combinations in the absence of high-risk HPV types does not identify women at increased 3-year risk for cervical precancer. Testing for HPV 6, 11, 42, or combinations of those types should be discontinued because it has no proven benefit to patients.II.

SUBMITTER: Castle PE

PROVIDER: S-EPMC3926945 | biostudies-literature | 2014 Jan

REPOSITORIES: biostudies-literature

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Three-year risk of cervical precancer and cancer after the detection of low-risk human papillomavirus genotypes targeted by a commercial test.

Castle Philip E PE Hunt William C WC Langsfeld Erika E Wheeler Cosette M CM

Obstetrics and gynecology 20140101 1

<h4>Objective</h4>To investigate the risk of cervical precancer and cancer associated with detection of human papillomavirus (HPV) 6, 11, and 42.<h4>Methods</h4>We used data from the New Mexico Human Papillomavirus Pap Registry. A stratified sample of 59,644 residual cervical cytology specimens from a population of 379,000 underwent HPV genotyping. We measured the 3-year cumulative incidence of cervical intraepithelial neoplasia grade 2 or more severe (CIN 2+) and grade 3 or more severe (CIN 3+) ...[more]

PMID: 24463663

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Project description:Previous studies have suggested an association between human papillomavirus type 16 (HPV16) genome methylation and cervical intraepithelial neoplasia grade 3 (CIN3) (ie, cervical precancer) and cancer, but the results have been inconsistent.We designed a case-control study within a large prospective cohort of women who underwent multiple screenings for cervical cancer in Guanacaste, Costa Rica. Diagnostic specimens were collected at the time of CIN3 diagnosis (n = 30 case subjects) and persistent HPV16 infection (persistence; n = 35 case subjects), prediagnostic specimens at the first HPV16-positive screening visit (n = 20 CIN3 case subjects; n = 35 persistence case subjects), and control specimens from women with infection clearance within 2 years (n = 34 control subjects). DNA extracted from specimens (cervical cells) was analyzed for methylation levels at 67 CpG sites throughout the HPV16 genome using pyrosequencing. Benjamini-Hochberg method was used to account for multiple testing. Associations between methylation levels and risk of CIN3 or persistence were assessed using logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (CIs).Increased methylation in diagnostic vs control specimens at nine CpG sites, three in each L1, L2, and E2/E4 genomic regions, was associated with an increased risk of CIN3 (third tertile [high] vs first and second tertiles combined [low], OR = 3.29 [95% CI = 1.16 to 9.34] to 11.12 [95% CI = 2.29 to 76.80]) and persistence. High methylation at three of these CpG sites was associated with a much higher risk when combined compared with low methylation at these sites (OR = 52, 95% CI = 4.0 to 670). In prediagnostic vs control specimens, increased methylation at a CpG site (nucleotide position 4261) in L2 was associated with an increased risk of CIN3.In this HPV16-infected cohort, increased methylation of CpG sites within the HPV16 genome before diagnosis and at the time of diagnosis was associated with cervical precancer.

Project description:ImportanceAs cervical cancer screening transitions to primary human papillomavirus (HPV) testing, effective triage and management of HPV-positive women is critical to avoid unnecessary colposcopy referral and associated harms while maintaining high sensitivity for cervical precancer. Triage with p16/Ki-67 dual-stain (DS) testing has shown high sensitivity and specificity for detection of cervical precancers; however, longitudinal studies are needed to determine the long-term risk of precancer following a negative DS result.ObjectiveTo evaluate the longitudinal performance of p16/Ki-67 DS triage for detection of cervical precancer in HPV-positive women over 5 years of follow-up in the context of clinical management thresholds.Design, setting, and participantsProspective cohort study of HPV-positive women 30 years or older undergoing routine cervical cancer screening in 2012 with HPV and Papanicolaou (hereinafter "cytology") co-testing within the Kaiser Permanente Northern California health care system. Follow-up of medical records was conducted through 2017.ExposuresAll p16/Ki-67 DS testing was performed on residual SurePath material, and slides were evaluated for p16/Ki-67 positivity.Main outcomes and measuresHistological end points were ascertained from the clinical database through 2017. We estimated 5-year cumulative risks of cervical intraepithelial neoplasia grades of 2 or worse (≥CIN2) or grades 3 or worse (≥CIN3) by baseline DS and cytology at yearly intervals using Logistic Weibull models. Risks were compared with clinical management thresholds for colposcopy referral and a 1-year return interval.ResultsAmong the 1549 HPV-positive women in this study, the mean age at enrollment was 42.2 years, and the median follow-up time was 3.7 years (range, 0.2-5.4 years). Positive DS results were associated with significantly higher cumulative 5-year risks of ≥CIN2 compared with abnormal cytology (31.0%; 95% CI, 27.2%-35.3% vs 25.0%; 95% CI, 21.7%-28.7%; P = .03). Women with DS-negative findings had significantly lower 5-year risks of ≥CIN2 compared with women with normal cytology (8.5%; 95% CI, 6.5%-11.1% vs 12.3%; 95% CI, 9.8%-15.4%; P = .04). In DS-negative women, the risks of both ≥CIN2 and ≥CIN3 remained below the colposcopy referral threshold for all 5 years, crossing the 1-year return threshold at 3 years.Conclusions and relevanceTriage with p16/Ki-67 DS provides better long-term risk stratification than cytology over 5 years. The low risk of cervical precancer in p16/Ki-67 DS-negative women permits safe extension of follow-up intervals for 3 years.

Dataset Information

Three-year risk of cervical precancer and cancer after the detection of low-risk human papillomavirus genotypes targeted by a commercial test.

Publications

Three-year risk of cervical precancer and cancer after the detection of low-risk human papillomavirus genotypes targeted by a commercial test.

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