Progression of HPV infection to detectable cervical lesions or clearance in adult women: Analysis of the control arm of the VIVIANE study

S Rachel Skinner, Cosette M Wheeler, Barbara Romanowski, Xavier Castellsagué, Eduardo Lazcano-Ponce, M Rowena Del Rosario-Raymundo, Carlos Vallejos, Galina Minkina, Daniel Pereira Da Silva, Shelly McNeil, Vera Prilepskaya, Irina Gogotadze, Deborah Money, Suzanne M Garland, Viktor Romanenko, Diane M Harper, Myron J Levin, Archana Chatterjee, Brecht Geeraerts, Frank Struyf, Gary Dubin, Marie-Cécile Bozonnat, Dominique Rosillon, Laurence Baril, VIVIANE Study Group, Marie-Pierre David, Alice Raillard, Sabrina Collas De Souza, Aurélie Le Plain, Dominique Descamps, Karin Hardt, Mary Greenacre, Stéphanie Delval, Jenny Andersson, R Verheijen, J Stapleton, E H Tay, S C Quek, M Martens, M Cruiskshank, G Girard, C Bouchard, K L Fong, A Ilancheran, V Patricio, K Julien, T M Stoney, M Ferguson, A Cruz, H Gomez Moreno, A Savitcheva, N Savani, C Chambers, P Fine, B Fox, J Hedrick, J Rosen, M Sperling, S Angsuwathana, A Tristram, B ter Harmsel, L Ferguson, T Poling, N Ilina, N Chakhtoura, W Utian, C Hansen, L Leeman, Anne Szarewski, S Rachel Skinner, Cosette M Wheeler, Barbara Romanowski, Xavier Castellsagué, Eduardo Lazcano-Ponce, M Rowena Del Rosario-Raymundo, Carlos Vallejos, Galina Minkina, Daniel Pereira Da Silva, Shelly McNeil, Vera Prilepskaya, Irina Gogotadze, Deborah Money, Suzanne M Garland, Viktor Romanenko, Diane M Harper, Myron J Levin, Archana Chatterjee, Brecht Geeraerts, Frank Struyf, Gary Dubin, Marie-Cécile Bozonnat, Dominique Rosillon, Laurence Baril, VIVIANE Study Group, Marie-Pierre David, Alice Raillard, Sabrina Collas De Souza, Aurélie Le Plain, Dominique Descamps, Karin Hardt, Mary Greenacre, Stéphanie Delval, Jenny Andersson, R Verheijen, J Stapleton, E H Tay, S C Quek, M Martens, M Cruiskshank, G Girard, C Bouchard, K L Fong, A Ilancheran, V Patricio, K Julien, T M Stoney, M Ferguson, A Cruz, H Gomez Moreno, A Savitcheva, N Savani, C Chambers, P Fine, B Fox, J Hedrick, J Rosen, M Sperling, S Angsuwathana, A Tristram, B ter Harmsel, L Ferguson, T Poling, N Ilina, N Chakhtoura, W Utian, C Hansen, L Leeman, Anne Szarewski

Abstract

The control arm of the phase III VIVIANE (Human PapillomaVIrus: Vaccine Immunogenicity ANd Efficacy; NCT00294047) study in women >25 years was studied to assess risk of progression from cervical HPV infection to detectable cervical intraepithelial neoplasia (CIN). The risk of detecting CIN associated with the same HPV type as the reference infection was analysed using Kaplan-Meier and multivariable Cox models. Infections were categorised depending upon persistence as 6-month persistent infection (6MPI) or infection of any duration. The 4-year interim analysis included 2,838 women, of whom 1,073 (37.8%) experienced 2,615 infections of any duration and 708 (24.9%) experienced 1,130 6MPIs. Infection with oncogenic HPV types significantly increased the risk of detecting CIN grade 2 or greater (CIN2+) versus non-oncogenic types. For 6MPI, the highest risk was associated with HPV-33 (hazard ratio [HR]: 31.9 [8.3-122.2, p < 0.0001]). The next highest risk was with HPV-16 (21.1 [6.3-70.0], p < 0.0001). Similar findings were seen for infections of any duration. Significant risk was also observed for HPV-18, HPV-31, and HPV-45. Concomitant HPV infection or CIN grade 1 or greater associated with a different oncogenic HPV type increased risk. Most women (79.3%) with an HPV infection at baseline cleared detectable infections of any duration, and 69.9% cleared a 6MPI. The risk of progression of HPV infection to CIN2+ in women >25 years in this study was similar to that in women 15-25 years in PATRICIA.

Keywords: CIN; HPV; VIVIANE; adult women; natural history.

© 2015 The Authors and GlaxoSmithKline. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.

Figures

Figure 1
Figure 1
Study flow chart: detection of HPV infections and CIN. A. Throughout study. B. Prevalent infection at baseline. C. Infection first detected during follow‐up. 1Infection detected at baseline and subsequently identified as being a 6MPI or 12MPI. 12MPI: 12‐month persistent infection; 6MPI: 6‐month persistent infection; CIN: cervical intraepithelial neoplasia; HPV: human papillomavirus; TVC: total vaccinated cohort.
Figure 2
Figure 2
Chance of clearance of an HPV infection of any duration according to HPV type. HPV: human papillomavirus; HPVI: HPV infection of any duration.

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