RNA extended interventional nucleic acid longitudinal study: Clinical performance of Aptima messenger RNA HPV testing in cervical cancer screening with a 9-year follow-up.

BACKGROUND: There is a need for additional longitudinal studies with the Aptima messenger RNA human papillomavirus test (AHPV) to support the safety of extended screening intervals. RNA-based extended interventional nucleic acid (REINA) provides relevant information on the clinical performance of AHPV. METHODS: This is a longitudinal prospective analysis of 1538 participants after AHPV and liquid-based cytology (LBC) co-test complemented with REINA interventional protocol with a second co-test 4 years after negative screening on 2000 women. Diagnostic accuracy and cumulative risks for CIN2+ up to 9 years were calculated for all test combinations. RESULTS: Sensitivity and specificity for CIN2+ were 96.9% and 88.0% for AHPV and 72.3% and 92.0% for LBC. Negative predictive value (NPV) and positive predictive value (PPV) of AHPV were 99.9% and 23.6%. The 5- and 9-year risks of AHPV-negative women were 0.4% and 1.0% (CIN2+) and 0.3% and 0.7% (CIN3+), a 73% and 64% lower risk than with negative LBC (p ≤ .002). REINA participants with an AHPV-positive result at second co-test after a negative AHPV in first round had a significantly lower 5-year risk of CIN2+ (11.1%) than AHPV-positive women with unknown HPV history (29.5%). CONCLUSIONS: Currently, this constitutes the longest European longitudinal study with AHPV testing in screening population. It reveals 99.9% NPV and a significant protective effect of a previous negative test 5 years after a new HPV infection. These findings support the safety of Aptima for screening intervals beyond 5 years. The risk of disease is lower 9 years after a negative AHPV test than 3 years after a negative LBC. High specificity and PPV of Aptima may benefit controlling overtreatment and colposcopy referrals.

Applying the Paris System for Reporting Urine Cytology Increases the Rate of Atypical Urothelial Cells in Benign Cases: A Need for Patient Management Recommendations.

The Paris System (TPS) for reporting urinary cytology attempts to unify the terminology in this field. OBJECTIVES: To analyze the impact of adopting TPS by measuring nomenclature agreement and cytohistological correlation. MATERIALS AND METHODS: Voided urine liquid-based cytology samples corresponding to 149 biopsy-proven cases (76 high-grade carcinomas, 40 low-grade carcinomas, and 33 benign lesions), were reclassified by the same pathologist using TPS. Diagnostic agreement and sensitivity for both nomenclature systems was measured. RESULTS: When using TPS, the rate of atypical samples increased 8 times (from 3 to 24.2%) in benign cases, 10 times (from 2.5 to 25%) in low-grade carcinomas, and 2.4 times (from 6.6 to 15.8%) in high-grade carcinomas. The false-positive rate (abnormal cytology in negative or low-grade carcinoma cases) increased from 11 to 34.2%. Sensitivity was higher (63 vs. 49%) with TPS at the expense of a lower specificity (73 vs. 91%). The agreement between both nomenclatures was moderate for negative and high-grade carcinoma cases (k = 0.42 and 0.56, respectively) and weak for low-grade tumors (k = 0.35). CONCLUSIONS: Adopting TPS for reporting urine cytology results in a considerable increase in atypical diagnoses, improving sensitivity but lowering specificity. Appropriate management recommendations for patients with an atypical cytological diagnosis are required.

Cervical cancer screening cotesting with cytology and MRNA HPV E6/E7 yields high rates of CIN2+ lesions in young women.

BACKGROUND: European guidelines recommend primary HPV testing for cervical cancer screening. However, the starting age remains to be defined, with an undecided window between 30 and 35 years. This pilot study compares the effectiveness of primary HPV testing to that of cytology for the detection of high-grade (CIN2+) lesions stratified by age. METHODS: Cotesting with LBC cytology and APTIMA® HPV (AHPV) was performed in 5053 women aged 25-65 in an opportunistic screening program in Madrid. AHPV-positive cases were referred to colposcopy and genotyped for HPV16 and 18/45 (AHPV-GT). Results were analyzed stratified in four age groups. RESULTS: 454 cases (9.0%) were AHPV-positive. Women under 35 had a 30.2% CIN2+ rate, compared to 21.9% and 20.4% for women aged 35-44 or 45-54. There was a significant increase (P < .05) in the rate of CIN2+ in AHPV-GT-positive women when compared to that for other HPV types (AHPV-other), being 43.3% versus 15.7%. AHPV-GT-positive women under 35 had significantly higher rates of CIN2+ lesions than any other age-group. The sensitivity of cytology for cervical CIN2+ in APHV-positive women was 60.6%. All 4 carcinomas, including one AHPV-negative endometrial adenocarcinoma, had abnormal cytology. All cervical CIN2+ lesions biopsied were AHPV-positive. CONCLUSIONS: Aptima HPV shows a significantly higher sensitivity for cervical CIN2+ lesions than cytology alone. Unexpectedly, AHPV-positive women under 35 had the highest incidence of CIN2+ lesions, particularly when they are HPV16/18/45-positive. Reconsidering HPV primary screening before the recommended age of 35 is warranted.