Nonavalent papillomavirus (HPV) vaccine has been licensed in December 2014 and is currently undergoing World Health Organization review for prequalification. Vaccination of girls with HPV bi-quadrivalent vaccines has been widely implemented in Europe and Spain. The bivalent vaccine (Cervarix®, GlaxoSmithKline) targets HPV 16/18, the quadrivalent vaccine (GARDASIL®/Silgard®, Merck&Co) target HPV 6/11/16/18 and the nonavalent vaccine (GARDASIL 9®, Merck&Co) targets HPV 6/11/16/18/31/33/45/52/58. The objetive was to describe squamous precancerous cervical lesions potentially prevented by the nonavalent vaccine compared to the bi-quadrivalent vaccines according to age.
Histologically confirmed cases of cervical intraepithelial neoplasia (CIN) grade 2 (CIN2, n=145) and grade 3-carcinoma in situ (CIN3-CIS, n=244) were studied (2009-2014) in a University Hospital in Spain. High risk HPV genotypes were detected by Linear Array HPV Genotyping test (Roche diagnostics, Mannheim, Germany). The proportion of CIN2-3 lesions potentially prevented by different vaccines was calculated for women 18 to 34, 35-44 and ≥45 years old (age group 1, 2 and 3, respectively). Cervical lesions with coinfection were attributed to the detected genotype belonging to the HPV group most commonly detected in invasive cervical cancer (hierarchical attribution).Ethics Committee of Clinical Investigation of Galicia approved this study. Women signed informed consent. Epidat 3.1 was used for statistical analysis
Bi-quadrivalent vaccines potentially prevented 59% CIN2 vs. 69% CIN3-CIS (p<0.001). Nonavalent vaccine potentially prevented 86% CIN2 and CIN3-CIS. Bi-quadrivalent/nonavalent vaccines potentially prevented 63/87%, 51/91% and 50/75% of CIN2 and 78/90%, 66/86% and 45/76% of CIN3-CIS in age group 1, 2 and 3, respectively. Impact of these vaccines in CIN2-3 tended to decrease with increasing age (p-trend <0.05). Potential absolute additional impact of nonavalent vaccine was 16%, 26% and 29% of CIN2-3 in age group 1, 2 and 3, respectively, (p<0.005).
In comparison with bi-tetravalent vaccine, nonavalent vaccine would reduce the gap between CIN2 and CIN3-CIS prevention. Although nonavalent vaccine impact on precancerous lesions decreased as women age increased, significant absolute additional impact was expected in all age groups, especially in women more than 35 years old. Age-specific impact of nonavalent vaccine should be taken into account in cost-effectiveness evaluations and in vaccinated population screening