Fraction of high-grade cervical intraepithelial lesions attributable to genotypes targeted by a nonavalent HPV vaccine in Galicia, Spain

Abstract

BackgroundHuman papillomavirus (HPV) bivalent and quadrivalent vaccines have been widely implemented in worldwide organized immunization programs. A nonavalent HPV vaccine is now available in several countries. The objective was to describe the fraction of squamous non-invasive high-grade cervical intraepithelial lesions attributable to genotypes targeted by bi-quadrivalent vaccines and by nonavalent vaccine according to age and diagnosis in women living in the city of Vigo (Galicia, Spain).MethodsCervical scrapings (2009–2014) of women with histological diagnosis of cervical intraepithelial neoplasia grade 2 (CIN2, n = 145) and grade 3-carcinoma in situ (CIN3-CIS, n = 244) were tested with Linear Array HPV Genotyping test (Roche diagnostics, Mannheim, Germany). Hierarchical estimation of the fraction attributable to HPV 16/18 or HPV 31/33/45/52/58 detected alone or in combination was calculated. Absolute additional fraction attributable to genotypes targeted by nonavalent vaccine compared to genotypes targeted by bi-quadrivalent vaccines was calculated as the increment of attributable cases with respect to all studied cases. Age group 1, 2 and 3 included women 18 to 34, 35–44 and ≥45 years old, respectively. EPIDAT 3.1 was used.ResultsFraction attributable to genotypes targeted by bi-quadrivalent vaccines was 59% CIN2 vs. 69% CIN3-CIS (p < 0.001). It was 63/51/50% of CIN2 and 78/66/45% of CIN3-CIS in age group 1, 2, 3, respectively. Fraction attributable to genotypes targeted by nonavalent vaccine was 86% CIN2 and 86% CIN3-CIS. It was 87/91/75% of CIN2 and 90/86/76% of CIN3-CIS in age group 1, 2, 3, respectively. Fraction attributable to genotypes targeted by these vaccines tended to decrease as age increased (p-trend <0.05). Globally, absolute additional attributable fraction was 16%, 26% and 29% in age group 1, 2 and 3, respectively (p < 0.005).ConclusionsAbsolute additional fraction of CIN2 and CIN3-CIS attributable to genotypes targeted by nonavalent vaccine was observed in women of any age, especially in those over 35 years old.

Age-Related Changes in the Fraction of Cervical Intraepithelial Neoplasia Grade 3 Related to HPV Genotypes Included in the Nonavalent Vaccine

“…Overall, our results are in line with these data since the fraction of CIN3 attributable to the genotypes included in the vaccine was 91.7%. In a recent study evaluating the fraction of CIN2+ due to genotypes included in the nonavalent HPV vaccine, Perez et al reported similar results with a percentage of CIN3-CIS covered by the vaccine of 86% [10].…”

“…Furthermore, the significant negative trend with age of HPV-16 and HPV-33 may explain the overall negative trend in expected vaccination protection reported by the present study. Before us, a previous study including 244 women with CIN3 also showed a significant negative trend with increasing age in the potential nonavalent HPV vaccine protection [10]. The authors demonstrated vaccine protection of 90/86/76% for CIN3/CIS in the same age groups (18–34, 35–44, and ≥45 years), respectively [10].…”

“…The rate of single and multiple HPV infections was measured. According to previous studies [10], when multiple HPV infections were present, a hierarchical attribution estimate was used. In this regard, CIN3 was attributed to the genotype most associated with high-grade cervical lesions or CCs.…”

Trend of HPV 16/18 Genotypes in Cervical Intraepithelial Neoplasia Grade 3: Data for 2007–2018

“…According to HPV genotype classifications, 18 , 19 they were classified as follows: 1) high-risk HPV (genotypes 16/18/31/33/35/39/45/51/52/56/58/59/66/68); 2) possibly carcinogenic HPVs (genotypes 26/30/53/67/70/73/82/85); 3) low-risk HPV (genotypes 6/11/40/42/43/44/54/55/61). Previous studies 20 , 21 have used hierarchical attribution in cases of multiple HPV infections. Based on this criterion, the CIN3 lesion was attributed to the genotype most associated with precancerous lesions of the uterine cervix: HPV 16/18 > all other HPVs; high-risk HPV > possibly carcinogenic HPV; possibly carcinogenic HPV > low-risk HPV.…”

“…Previous studies20,21 have used hierarchical attribution in cases of multiple HPV infections. Based on this criterion, the CIN3 lesion was attributed to the genotype most associated with precancerous lesions of the uterine cervix:HPV16/18 > all other HPVs; high-risk HPV > possibly carcinogenic HPV; possibly carcinogenic HPV > low-risk HPV.…”