TY - JOUR T1 - Persistent High-Risk Human Papillomavirus Infections and Other End-Point Markers of Progressive Cervical Disease Among Women Prospectively Followed up in the New Independent States of the Former Soviet Union and the Latin American Screening Study Cohorts JF - International Journal of Gynecologic Cancer JO - Int J Gynecol Cancer SP - 934-942 LP - 934-942 DO - 10.1111/IGC.0b013e3181a834fe VL - 19 IS - 5 AU - Kari SyrjÄNen AU - Irena Shabalova AU - Paulo Naud AU - Vladimir Kozachenko AU - Sophie Derchain AU - Sergej Zakharchenko AU - Cecilia Roteli-Martins AU - Raisa Nerovjna AU - Adhemar Longatto-Filho AU - Ludmila Kljukina AU - Silvio Tatti AU - Marina Branovskaja AU - Luciano Serpa Hammes AU - Margherita Branca AU - Valerija Grunjberga AU - Mojca ErŽEn AU - Luis Otavio Sarian AU - Anna Juschenko AU - Silvano Costa AU - Jurij Podistov AU - Stina SyrjÄNen AU - the NIS and LAMS Study Research Groups Y1 - 2009/07/01 UR - http://ijgc.bmj.com/content/19/5/934-942.abstract N2 - Background: New end points are needed in future human papillomavirus (HPV) vaccine efficacy studies that accurately predict disease progression.Objectives: Potential intermediate end points were analyzed in the combined New Independent States of the Former Soviet Union (NIS) and the Latin American Screening (LAMS) study cohorts.Study Design and Methods: Data files of 2 international screening trials, the NIS (n = 3187) and the LAMS (n = 12,114) study cohorts, were combined, and a subcohort of 1865 (n = 854 and n = 1011 for the NIS and the LAMS, respectively) women prospectively followed up for 19.7 (median, 22.2) months was analyzed for different intermediate end-point markers of disease progression to squamous intraepithelial lesion (SIL), cervical intraepithelial neoplasia grade 1 and higher (CIN1+), and CIN grade 2 and higher (CIN2+) as terminal events.Results: Altogether, 131 (7.0%), 90 (4.8%), and 39 (2.1%) cases progressed to SIL, CIN1+, and CIN2+, respectively, progression times being equal in the NIS (11.9, 16.8, and 19.6 months) and LAMS (13.6, 14.1, and 15.4 months) cohorts (P = 0.931, P = 0.335, and P = 0.535). The 2 most powerful end-point markers of disease progression to CIN2+ were high-grade squamous intraepithelial lesions based on Papanicolaou test results at 6-month (odds ratio [OR] = 47.1; 95% confidence interval [CI], 17.3-128.7) and 12-month (OR = 21.5; 95% CI, 5.1-90.8) follow-up visits, with longitudinal positive and negative predictive values of 42.1% and 98.0% (6 months) and 33.3% and 97.7% (12 months). Of the virological end points, more than 6 months of persistent high-risk HPV (HR-HPV) was the most powerful predictor of progression to CIN1+ (OR = 18.6; 95% CI, 2.5-136.5), with longitudinal positive and negative predictive values of 10.3% and 99.4%, respectively. No additional benefit was obtained using more than 12 months of persistent HR-HPV end point.Conclusions: High-grade squamous intraepithelial lesion based on a Papanicolaou test results at 6- or 12-month follow-up visits was the most powerful end point, either considering cytological end points alone or in comparison to any of the virological end points. Of the virological end points, more than 6-month HR-HPV persistence criteria give the most powerful estimate of a progressive disease. ER -