Human papillomavirus and risk to pregnancy: a cohort study

Human papillomavirus (HPV) is the most common sexually transmitted infection (STI), and a major concern as high-risk genotypes cause cervical and other cancers. Beyond cancer risk, there is growing evidence that HPV may be associated with adverse pregnancy outcomes. Indeed, studies show that HPV is highly prevalent during pregnancy, can infect the cervix, amniotic fluid, and placenta, and may increase the risk of preterm birth, a leading cause of infant mortality. Preterm birth is common with a prevalence of 10%. Therefore, it is important to determine if HPV is a contributor. However, a closer examination of the literature shows that studies examining the relationship between HPV and preterm birth have been highly mixed and fraught with limitations including retrospective study designs, HPV measurement error, and confounding variables. There have been two prospective cohorts conducted recently to address these limitations, one utilizing vaginal swabs at two time-points that found an association between HPV and preterm birth, and another study of urine samples that found no significant association. There remains a significant need for large-scale studies in the US to examine the impact of prenatal HPV on risk of adverse pregnancy outcomes. We propose the HPV And Risk to Pregnancy (HARP) Study, a prospective cohort of 1280 pregnancies from three clinics at the University of Texas Medical Branch. To add to the current literature, our objective is to determine if vaginal high-risk HPV infection at ≤20 weeks gestation, or persistent or new infection in the third trimester, is associated with preterm birth. We will address understudied aspects of this field of study, such as the association between prenatal HPV infection and hypertensive disorders of pregnancy, which are common contributors to preterm birth. We will also investigate new aspects of this area of study, such as determining the association between HPV-chlamydia co-infection on risk of preterm birth and hypertensive disorders of pregnancy. This is novel and aligned with experimental data that has shown that HPV co-infection with chlamydia impacts cervical integrity and enhances cervical cancer pathology. Our multidisciplinary team has the expertise to ensure the success of the HARP study. If our hypotheses are correct, this study may have significant sustained contributions to the field by opening the door for deliberate discussions on the potential for prenatal HPV screening.