Risk of recurrent spontaneous preterm birth among those with persistent cervical HPV infection

Preterm premature rupture of membranes (PPROM) and preterm labor (PTL) are adverse obstetrical outcomes that are strongly associated with cervical high-risk human papilloma virus (cHPV) infection at the time of pregnancy. Persistent cHPV may lead to oncogenic changes in the cervico-vaginal tract and can cause inflammation in gestational tissues, but it is unknown how persistent cHPV infection may affect obstetrical outcomes. The aim of this study is to evaluate whether persistent cHPV infection is associated with recurrent PPROM or PTL among patients with a prior spontaneous preterm birth due to PPROM/PTL, and to examine clinical and pathologic characteristics of cHPV infection in this population.

We conducted a retrospective cohort study of patients delivering at Mayo Clinic Rochester or Mayo Clinic Health System (5/1/2018-12/31/2023). Eligible patients had ≥ 1 spontaneous preterm birth due to PPROM/PTL and positive cHPV testing. Demographics and pregnancy outcomes from index and subsequent pregnancies were abstracted. Persistent cHPV was defined as > 1 pregnancy with positive cHPV testing.

Of 191 index pregnancies, 90 (47.1%) and 30 (33.3%) had one and two subsequent pregnancies, respectively. Patients were predominantly White (91.3%), non-Hispanic (94.2%), non-smokers (72.0%), and 34.8% were unvaccinated for HPV. Approximately one-third (31%) experienced recurrent PPROM/PTL in the second pregnancy, with recurrence in 40.7% of those with persistent cHPV and 27.4% without (p = 0.69). Excisional procedures occurred before 12.0% of index pregnancies and 20-24% of subsequent pregnancies; recurrence of PTL/PPROM remained high regardless of procedure history. HPV strain data were available for 132 index pregnancies, and types 16 and 18 were more likely to persist into a subsequent pregnancy (p = 0.0043). CIN persistence occurred at similar rates in patients with and without persistent cHPV infection. Placental inflammation rates were high in both patients with persistent and non-persistent cHPV.

Recurrent PPROM/PTL, CIN persistence, and placental inflammation were common; a finding independent of persistent cHPV infection, excisional procedure history, or HPV vaccination status. These findings suggest that factors other than cHPV persistence may play a larger role in recurrent preterm birth. Larger studies with higher cHPV prevalence and subsequent pregnancies are needed to provide clarity.