Corrigendum to "Use of the nonavalent HPV vaccine in individuals previously fully or partially vaccinated with bivalent or quadrivalent HPV vaccines" [Vaccine 34 (2016) 757–761]

n/

Predictors of human papillomavirus infection in women undergoing routine cervical cancer screening in Spain : the CLEOPATRE study

Human papillomavirus (HPV) is a sexually transmitted infection that may lead to development of precancerous and cancerous lesions of the cervix. The aim of the current study was to investigate socio-demographic, lifestyle, and medical factors for potential associations with cervical HPV infection in women undergoing cervical cancer screening in Spain. The CLEOPATRE Spain study enrolled 3 261 women aged 18-65 years attending cervical cancer screening across the 17 Autonomous Communities. Liquid-based cervical samples underwent cytological examination and HPV testing. HPV positivity was determined using the Hybrid Capture II assay, and HPV genotyping was conducted using the INNO-LiPA HPV Genotyping Extra assay. Multivariate logistic regression was used to identify putative risk factors for HPV infection. A lifetime number of two or more sexual partners, young age (18-25 years), a history of genital warts, and unmarried status were the strongest independent risk factors for HPV infection of any type. Living in an urban community, country of birth other than Spain, low level of education, and current smoking status were also independent risk factors for HPV infection. A weak inverse association between condom use and HPV infection was observed. Unlike monogamous women, women with two or more lifetime sexual partners showed a lower risk of infection if their current partner was circumcised (P for interaction, 0.005) and a higher risk of infection if they were current smokers (P for interaction, 0.01). This is the first large-scale, country-wide study exploring risk factors for cervical HPV infection in Spain. The data strongly indicate that variables related to sexual behavior are the main risk factors for HPV infection. In addition, in non-monogamous women, circumcision of the partner is associated with a reduced risk and smoking with an increased risk of HPV infection

Predictors of human papillomavirus infection in women undergoing routine cervical cancer screening in Spain: the CLEOPATRE study

Background: Human papillomavirus (HPV) is a sexually transmitted infection that may lead to development of precancerous and cancerous lesions of the cervix. The aim of the current study was to investigate sociodemographic, lifestyle, and medical factors for potential associations with cervical HPV infection in women undergoing cervical cancer screening in Spain. Methods: The CLEOPATRE Spain study enrolled 3 261 women aged 18–65 years attending cervical cancer screening across the 17 Autonomous Communities. Liquid-based cervical samples underwent cytological examination and HPV testing. HPV positivity was determined using the Hybrid Capture II assay, and HPV genotyping was conducted using the INNO-LiPA HPV Genotyping Extra assay. Multivariate logistic regression was used to identify putative risk factors for HPV infection. Results: A lifetime number of two or more sexual partners, young age (18–25 years), a history of genital warts, and unmarried status were the strongest independent risk factors for HPV infection of any type. Living in an urban community, country of birth other than Spain, low level of education, and current smoking status were also independent risk factors for HPV infection. A weak inverse association between condom use and HPV infection was observed. Unlike monogamous women, women with two or more lifetime sexual partners showed a lower risk of infection if their current partner was circumcised (P for interaction, 0.005) and a higher risk of infection if they were current smokers (P for interaction, 0.01). Conclusion: This is the first large-scale, country-wide study exploring risk factors for cervical HPV infection in Spain. The data strongly indicate that variables related to sexual behavior are the main risk factors for HPV infection. In addition, in non-monogamous women, circumcision of the partner is associated with a reduced risk and smoking with an increased risk of HPV infection

Association between Common Germline Genetic Variation in 94 Candidate Genes or Regions and Risks of Invasive Epithelial Ovarian Cancer

Background: Recent studies have identified several single nucleotide polymorphisms (SNPs) in the population that are associated with variations in the risks of many different diseases including cancers such as breast, prostate and colorectal. For ovarian cancer, the known highly penetrant susceptibility genes (BRCA1 and BRCA2) are probably responsible for only 40% of the excess familial ovarian cancer risks, suggesting that other susceptibility genes of lower penetrance exist.Methods: We have taken a candidate approach to identifying moderate risk susceptibility alleles for ovarian cancer. To date, we have genotyped 340 SNPs from 94 candidate genes or regions, in up to 1,491 invasive epithelial ovarian cancer cases and 3,145 unaffected controls from three different population based studies from the UK, Denmark and USA.Results: After adjusting for population stratification by genomic control, 18 SNPs (5.3%) were significant at the 5% level, and 5 SNPs (1.5%) were significant at the 1% level. The most significant association was for the SNP rs2107425, located on chromosome 11p15.5, which has previously been identified as a susceptibility allele for breast cancer from a genome wide association study (P-trend = 0.0012). When SNPs/genes were stratified into 7 different pathways or groups of validation SNPs, the breast cancer associated SNPs were the only group of SNPs that were significantly associated with ovarian cancer risk (P-heterogeneity = 0.0003; P-trend = 0.0028; adjusted (for population stratification) P-trend = 0.006). We did not find statistically significant associations when the combined data for all SNPs were analysed using an admixture maximum likelihood (AML) experiment- wise test for association (P-heterogeneity = 0.051; P-trend = 0.068).Conclusion: These data suggest that a proportion of the SNPs we evaluated were associated with ovarian cancer risk, but that the effect sizes were too small to detect associations with individual SNPs

Human papillomavirus detection in cervical neoplasia attributed to 12 high-risk human papillomavirus genotypes by region

Background: We estimated the proportion of cervical intraepithelial neoplasia (CIN) cases attributed to 14 HPV types, including quadrivalent (qHPV) (6/11/16/18) and 9-valent (9vHPV) (6/11/16/18/31/33/45/52/58) vaccine types, by region Methods: Women ages 15-26 and 24-45 years from 5 regions were enrolled in qHPV vaccine clinical trials. Among 10,706 women (placebo arms), 1539 CIN1, 945 CIN2/3, and 24 adenocarcinoma in situ (AIS) cases were diagnosed by pathology panel consensus. Results: Predominant HPV types were 16/51/52/56 (anogenital infection), 16/39/51/52/56 (CIN1), and 16/31/52/58 (CIN2/3). In regions with largest sample sizes, minimal regional variation was observed in 9vHPV type prevalence in CIN1 (similar to 50%) and CIN2/3 (81-85%). Types 31/33/45/52/58 accounted for 25-30% of CIN1 in Latin America and Europe, but 14-18% in North America and Asia. Types 31/33/45/52/58 accounted for 33-38% of CIN2/3 in Latin America (younger women), Europe, and Asia, but 17-18% of CIN2/3 in Latin America (older women) and North America. Non-vaccine HPV types 35/39/51/56/59 had similar or higher prevalence than qHPV types in CIN1 and were attributed to 2-11% of CIN2/3. Conclusions: The 9vHPV vaccine could potentially prevent the majority of CIN1-3, irrespective of geographic region. Notwithstanding, non-vaccine types 35/39/51/56/59 may still be responsible for some CIN1, and to a lesser extent CIN2/3. (C) 2016 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)

Population-based targeted sequencing of 54 candidate genes identifies PALB2 as a susceptibility gene for high-grade serous ovarian cancer

Purpose: The known epithelial ovarian cancer (EOC) susceptibility genes account for less than 50% of the heritable risk of ovarian cancer suggesting that other susceptibility genes exist. The aim of this study was to evaluate the contribution to ovarian cancer susceptibility of rare deleterious germline variants in a set of candidate genes. Methods: We sequenced the coding region of 54 candidate genes in 6385 invasive EOC cases and 6115 controls of broad European ancestry. Genes with an increased frequency of putative deleterious variants in cases versus controls were further examined in an independent set of 14 135 EOC cases and 28 655 controls from the Ovarian Cancer Association Consortium and the UK Biobank. For each gene, we estimated the EOC risks and evaluated associations between germline variant status and clinical characteristics. Results: The ORs associated for high-grade serous ovarian cancer were 3.01 for PALB2 (95% CI 1.59 to 5.68; p=0.00068), 1.99 for POLK (95% CI 1.15 to 3.43; p=0.014) and 4.07 for SLX4 (95% CI 1.34 to 12.4; p=0.013). Deleterious mutations in FBXO10 were associated with a reduced risk of disease (OR 0.27, 95% CI 0.07 to 1.00, p=0.049). However, based on the Bayes false discovery probability, only the association for PALB2 in high-grade serous ovarian cancer is likely to represent a true positive. Conclusions: We have found strong evidence that carriers of PALB2 deleterious mutations are at increased risk of high-grade serous ovarian cancer. Whether the magnitude of risk is sufficiently high to warrant the inclusion of PALB2 in cancer gene panels for ovarian cancer risk testing is unclear; much larger sample sizes will be needed to provide sufficiently precise estimates for clinical counselling

Association between invasive ovarian cancer susceptibility and 11 best candidate SNPs from breast cancer genome-wide association study

Because both ovarian and breast cancer are hormone-related and are known to have some predisposition genes in common, we evaluated 11 of the most significant hits (six with confirmed associations with breast cancer) from the breast cancer genome-wide association study for association with invasive ovarian cancer. Eleven SNPs were initially genotyped in 2927 invasive ovarian cancer cases and 4143 controls from six ovarian cancer case–control studies. Genotype frequencies in cases and controls were compared using a likelihood ratio test in a logistic regression model stratified by study. Initially, three SNPs (rs2107425 in MRPL23, rs7313833 in PTHLH, rs3803662 in TNRC9) were weakly associated with ovarian cancer risk and one SNP (rs4954956 in NXPH2) was associated with serous ovarian cancer in non-Hispanic white subjects (P-trend < 0.1). These four SNPs were then genotyped in an additional 4060 cases and 6308 controls from eight independent studies. Only rs4954956 was significantly associated with ovarian cancer risk both in the replication study and in combined analyses. This association was stronger for the serous histological subtype [per minor allele odds ratio (OR) 1.07 95% CI 1.01–1.13, P-trend = 0.02 for all types of ovarian cancer and OR 1.14 95% CI 1.07–1.22, P-trend = 0.00017 for serous ovarian cancer]. In conclusion, we found that rs4954956 was associated with increased ovarian cancer risk, particularly for serous ovarian cancer. However, none of the six confirmed breast cancer susceptibility variants we tested was associated with ovarian cancer risk. Further work will be needed to identify the causal variant associated with rs4954956 or elucidate its function

Consortium analysis of 7 candidate SNPs for ovarian cancer

The Ovarian Cancer Association Consortium selected 7 candidate single nucleotide polymorphisms (SNPs), for which there is evidence from previous studies of an association with variation in ovarian cancer or breast cancer risks. The SNPs selected for analysis were F31I (rs2273535) in AURKA, N372H (rs144848) in BRCA2, rs2854344 in intron 17 of RB1, rs2811712 5′ flanking CDKN2A, rs523349 in the 3′ UTR of SRD5A2, D302H (rs1045485) in CASP8 and L10P (rs1982073) in TGFB1. Fourteen studies genotyped 4,624 invasive epithelial ovarian cancer cases and 8,113 controls of white non-Hispanic origin. A marginally significant association was found for RB1 when all studies were included [ordinal odds ratio (OR) 0.88 (95% confidence interval (CI) 0.79-1.00) p = 0.041 and dominant OR 0.87 (95% CI 0.76-0.98) p = 0.025]; when the studies that originally suggested an association were excluded, the result was suggestive although no longer statistically significant (ordinal OR 0.92, 95% CI 0.79-1.06). This SNP has also been shown to have an association with decreased risk in breast cancer. There was a suggestion of an association for AURKA, when one study that caused significant study heterogeneity was excluded [ordinal OR 1.10 (95% CI 1.01-1.20) p = 0.027; dominant OR 1.12 (95% CI 1.01-1.24) p = 0.03]. The other 5 SNPs in BRCA2, CDKN2A, SRD5A2, CASP8 and TGFB1 showed no association with ovarian cancer risk; given the large sample size, these results can also be considered to be informative. These null results for SNPs identified from relatively large initial studies shows the importance of replicating associations by a consortium approach