Mónica S Sierra

Risk Factors for Non–Human Papillomavirus (HPV) Type 16/18 Cervical Infections and Associated Lesions Among HPV DNA–Negative Women Vaccinated Against HPV-16/18 in the Costa Rica Vaccine Trial

AbstractBackgroundFactors that lead human papillomavirus (HPV) infections to persist and progress to cancer are not fully understood. We evaluated co-factors for acquisition, persistence, and progression of non–HPV-16/18 infections among HPV-vaccinated women.MethodsWe analyzed 2153 women aged 18–25 years randomized to the HPV-vaccine arm of the Costa Rica HPV Vaccine Trial. Women were HPV DNA negative for all types at baseline and followed for approximately 11 years. Generalized estimating equation methods were used to account for correlated observations. Time-dependent factors evaluated were age, sexual behavior, marital status, hormonally related factors, number of full-term pregnancies (FTPs), smoking behavior, and baseline body mass index.ResultsA total of 1777 incident oncogenic non–HPV-16/18 infections were detected in 12 292 visits (average, 0.14 infections/visit). Age and sexual behavior–related variables were associated with oncogenic non–HPV-16/18 acquisition. Twenty-six percent of incident infections persisted for ≥1 year. None of the factors evaluated were statistically associated with persistence of oncogenic non–HPV-16/18 infections. Risk of progression to Cervical Intraepithelial Neoplasia grade 2 or worst (CIN2+) increased with increasing age (P for trend = .001), injectable contraceptive use (relative risk, 2.61 [95% confidence interval, 1.19–5.73] ever vs never), and increasing FTPs (P for trend = .034).ConclusionsIn a cohort of HPV-16/18–vaccinated women, age and sexual behavior variables are associated with acquisition of oncogenic non–HPV-16/18 infections; no notable factors are associated with persistence of acquired infections; and age, parity, and hormonally related exposures are associated with progression to CIN2+.

Validation of TypeSeq2, a Next-Generation–Based Sequencing Assay for the Detection of 46 Human Papillomavirus Genotypes, at the US National Cancer Institute and Costa Rica Laboratories

Abstract Background Cervical cancer is caused by persistent infection with carcinogenic human papillomavirus (HPV) genotypes. Prophylactic HPV vaccines are highly efficacious in preventing the acquisition of HPV infection. HPV vaccine trials and epidemiologic studies based on virologic endpoints rely on valid and reproducible measurements of HPV. We evaluated the second version of TypeSeq (TS2), a next-generation, sequencing-based assay that detects 46 HPV genotypes, in a historical phase 3 clinical trial. Methods We used 1214 stored cervical samples from women enrolled in the Costa Rica HPV Vaccine Trial with available HPV results from Short PCR Fragment 10- Line Probe Assay 25 (SPF10-LiPA25). TS2 was first validated at the National Cancer Institute (NCI) and transferred to the laboratory in Costa Rica, where we conducted a second validation study. We compared TS2 results generated at each laboratory to the SPF10-LiPA25 results. Results Overall, each laboratory demonstrated high positive agreement for most carcinogenic and noncarcinogenic genotypes between TS2 and SPF10-LiPA25. Intralaboratory comparisons revealed very high agreement in repeated testing. Interlaboratory comparisons showed high agreement for most carcinogenic and noncarcinogenic types. Overall, there were no statistically significant differences in vaccine efficacy in the according-to-protocol cohort using TS2 (either in NCI or Costa Rica) or SPF10-LiPA25 (McNemar P values >.05). Costa Rica produced similar vaccine efficacy estimates as NCI for HPV16/18, HPV31/33/45, and HPV35/39/51/52/56/58/59 as NCI (P values ≥.36). Conclusions Compared to SPF10-LiPA25, a well-established standard for HPV genotyping, TS2 demonstrated high accuracy. Inter- and intralaboratory comparisons demonstrated that TS2 is valid and reproducible. TS2 can accurately classify the presence of HPV, which is essential in HPV vaccine trials evaluating virological endpoints. Clinical Trials Registration NCT00128661.