Karin Sundström1, Alexander Ploner1, Lisen Arnheim-Dahlström2, Sandra Eloranta2, Juni Palmgren2, Hans-Olov Adami2, Nathalie Ylitalo Helm2, Pär Sparén2, Joakim Dillner2. 1. Department of Laboratory Medicine (KS, JD), Department of Medical Epidemiology and Biostatistics (AP, LAD, JP, HOA, PS, JD), and Department of Medicine, Clinical Epidemiology Unit (SE), Karolinska Institutet, Stockholm, Sweden; Swedish eScience Research Center, Stockholm, Sweden (JP); Institute for Molecular Medicine Finland, Helsinki University, Helsinki, Finland (JP); Department of Epidemiology, Harvard School of Public Health, Boston, MA (HOA); Division of Clinical Cancer Epidemiology, Department of Oncology, Sahlgrenska University Hospital, Gothenburg, Sweden (NYH). karin.sundstrom@ki.se. 2. Department of Laboratory Medicine (KS, JD), Department of Medical Epidemiology and Biostatistics (AP, LAD, JP, HOA, PS, JD), and Department of Medicine, Clinical Epidemiology Unit (SE), Karolinska Institutet, Stockholm, Sweden; Swedish eScience Research Center, Stockholm, Sweden (JP); Institute for Molecular Medicine Finland, Helsinki University, Helsinki, Finland (JP); Department of Epidemiology, Harvard School of Public Health, Boston, MA (HOA); Division of Clinical Cancer Epidemiology, Department of Oncology, Sahlgrenska University Hospital, Gothenburg, Sweden (NYH).
Abstract
BACKGROUND: The clinical significance of co-infections with high-risk (HR) and low-risk (LR) human papillomavirus (HPV) in the etiology of cervical cancer is debated, as prospective evidence on this issue is limited. However, the question is of increasing relevance in relation to HPV-based cancer prevention. METHODS: In two population-based nested case-control studies among women participating in cervical screening with baseline normal smears, we collected 4659 smears from women who later developed cancer in situ (CIS; n = 524) or squamous cervical cancer (SCC; n = 378) and individually matched control subjects who remained free of disease during study follow-up. The median follow-up until diagnosis was 6.4 to 7.8 years. All smears were tested for HPV. We used conditional logistic regression models with two-way interaction terms to estimate relative risks (RRs) for CIS and SCC, respectively. All statistical tests were two-sided. RESULTS: Compared with women who were infected with HRHPV only, women who were also infected with LRHPV had a lower risk for SCC (RR = 0.2, 95% confidence interval [CI] = 0.04 to 0.99, P = .049). This interaction was not shown for CIS (RR = 1.1, 95% CI = 0.4 to 3.6). Women who were positive for both HRHPV and LRHPV had, on average, a 4.8 year longer time to diagnosis of SCC than women who were positive for HRHPV only (P = .006). Results were highly robust in sensitivity analyses. CONCLUSION: Co-infection with LRHPV is associated with a lower risk of future invasive disease and longer time to diagnosis than infection with HRHPV alone. We propose that co-infection with LRHPV interferes with the rate of progression to invasive cervical cancer.
BACKGROUND: The clinical significance of co-infections with high-risk (HR) and low-risk (LR) human papillomavirus (HPV) in the etiology of cervical cancer is debated, as prospective evidence on this issue is limited. However, the question is of increasing relevance in relation to HPV-based cancer prevention. METHODS: In two population-based nested case-control studies among women participating in cervical screening with baseline normal smears, we collected 4659 smears from women who later developed cancer in situ (CIS; n = 524) or squamous cervical cancer (SCC; n = 378) and individually matched control subjects who remained free of disease during study follow-up. The median follow-up until diagnosis was 6.4 to 7.8 years. All smears were tested for HPV. We used conditional logistic regression models with two-way interaction terms to estimate relative risks (RRs) for CIS and SCC, respectively. All statistical tests were two-sided. RESULTS: Compared with women who were infected with HRHPV only, women who were also infected with LRHPV had a lower risk for SCC (RR = 0.2, 95% confidence interval [CI] = 0.04 to 0.99, P = .049). This interaction was not shown for CIS (RR = 1.1, 95% CI = 0.4 to 3.6). Women who were positive for both HRHPV and LRHPV had, on average, a 4.8 year longer time to diagnosis of SCC than women who were positive for HRHPV only (P = .006). Results were highly robust in sensitivity analyses. CONCLUSION: Co-infection with LRHPV is associated with a lower risk of future invasive disease and longer time to diagnosis than infection with HRHPV alone. We propose that co-infection with LRHPV interferes with the rate of progression to invasive cervical cancer.
Authors: Ilvars Silins; Zhaohui Wang; Elisabeth Åvall-Lundqvist; Bo Frankendal; Uldis Vikmanis; Martin Sapp; John T Schiller; Joakim Dillner Journal: J Gen Virol Date: 1999-11 Impact factor: 3.891
Authors: Filipa Godoy-Vitorino; Josefina Romaguera; Chunyu Zhao; Daniela Vargas-Robles; Gilmary Ortiz-Morales; Frances Vázquez-Sánchez; Maria Sanchez-Vázquez; Manuel de la Garza-Casillas; Magaly Martinez-Ferrer; James Robert White; Kyle Bittinger; Maria Gloria Dominguez-Bello; Martin J Blaser Journal: Front Microbiol Date: 2018-10-23 Impact factor: 5.640
Authors: Daniela Vargas-Robles; Magda Magris; Natalia Morales; Maurits N C de Koning; Iveth Rodríguez; Tahidid Nieves; Filipa Godoy-Vitorino; Gloria I Sánchez; Luis David Alcaraz; Larry J Forney; María-Eglée Pérez; Luis García-Briceño; Leen-Jan van Doorn; María Gloria Domínguez-Bello Journal: mSphere Date: 2018-05-02 Impact factor: 4.389