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Background: Human papillomavirus (HPV) testing is more sensitive than cytology for detecting high-grade cervical intraepithelial neoplasia (CIN). We evaluated the performance of high-risk HPV (hrHPV) testing in routine screening.Methods: In all, 25,871 women (29-61) enrolled in our population-based cohort study were offered both cytology and hrHPV testing. High-risk HPV-positive women with normal cytology and an age-matched subcohort of hrHPV-negative women with normal cytology were invited for repeat testing after 1 and/or 2 years and were referred for colposcopy if they presented with abnormal cytology and/or a positive hrHPV test. The hrHPV-positive women with borderline or mild dyskaryosis (BMD) and all women with moderate dyskaryosis or worse (>BMD) were directly referred for colposcopy. Women with BMD and an hrHPV-negative test were advised to repeat cytology at 6 and 18 months and were referred for colposcopy if the repeat cytology test was abnormal. The main outcome measure was CIN grade 3 or worse (CIN3+). Results were adjusted for non-attendance at repeat testing.Results: The hrHPV-positive women with abnormal cytology had a CIN3+ risk of 42.2% (95% confidence interval (CI): 36.4-48.2), whereas the hrHPV-positive women with normal cytology had a much lower risk of 5.22% (95% CI: 3.72-7.91). In hrHPV-positive women with normal cytology, an additional cytology step after 1 year reduced the CIN3+ risk to only 1.6% (95% CI: 0.6-4.9) if the repeat test was normal. The CIN3+ risk in women with hrHPV-positive normal cytology was higher among women invited for the first time (29-33 years of age) (9.1%; 95% CI: 5.6-14.3) than among older women (3.0%; 95% CI: 1.5-5.5).Conclusion: Primary hrHPV screening with cytology triage in women aged 30 years is an effective way to stratify women on CIN3+ risk and seems a feasible alternative to cytological screening. Repeat cytology after 1 year for hrHPV-positive women with normal cytology is however necessary before returning women to routine screening. [ABSTRACT FROM AUTHOR]

RATIONALE: Autofluorescence bronchoscopy (AFB) is a valid strategy for detecting premalignant endobronchial lesions. However, no biomarker can reliably predict lung cancer risk of subjects with AFB-visualized premalignant lesions. OBJECTIVES: The present study set out to identify AFB-visualized squamous metaplastic (SqM) lesions with malignant potential by DNA copy number profiling. METHODS: Regular AFB examinations in 474 subjects at risk of lung cancer identified six subjects with SqM lesions at baseline, and carcinoma in situ or carcinoma (carcinoma in situ or greater) at the initial SqM site at follow-up bronchoscopy. These progressive SqM lesions were compared for immunostaining pattern and array comparative genomic hybridization-based chromosomal profiles with 23 SqM lesions of subjects who remained cancer-free. Specific DNA copy number alterations (CNAs) linked to cancer risk were identified and accuracy of CNAs to predict endobronchial cancer in this series was determined. MEASUREMENTS AND MAIN RESULTS: At baseline, p53, p63, and Ki-67 immunostaining were not predictive for a differential clinical outcome of SqM lesions. The mean number of CNAs in baseline SqM of cases was significantly higher compared with control subjects (P < 0.01). Chromosomal regions significantly more frequently altered in SqM of cases were 3p26.3-p11.1, 3q26.2-q29, 9p13.3-p13.2, and 17p13.3-p11.2 (family-wise error rate <0.10). CNAs were specifically detected at the site of future cancer. In cases, baseline-detected CNAs persisted in subsequent biopsies taken from the initial site, and levels increased toward cancer progression. In this series, a model based on CNAs at 3p26.3-p11.1, 3q26.2-29, and 6p25.3-24.3 predicted cancer with 97% accuracy. CONCLUSIONS: The data suggest that the presence of specific CNAs in SqM lesions predict endobronchial cancer. [ABSTRACT FROM AUTHOR]