A persistent human papillomavirus (HPV) infection is a prerequisite for a HPV related cancer to develop. Asymptomatic, persistent HPV infections are not only found in genital tract, but also on oral mucosa. Oral HPV persistence may be associated with behavioural factors, but data on the role of innate immunity in oral HPV infections are still limited. Salivary concentrations of matrix metalloproteinases MMP-8 and MMP-9, tissue inhibitor of MMPs (TIMP-1), myeloperoxidase, and serum concentrations of MMP-8 were analysed in women with a persistent oral HPV infection and, as a control, in women who remained HPV DNA-negative during a 6-year follow-up. The effects of smoking, lactation and alcohol use on the salivary and serum parameters were assessed, too. A nested case-control setting was used to select a subgroup of 57 women with a persistent oral HPV infection and 102 controls from the Finnish Family HPV Study. The salivary MMP-8/TIMP-1 molar ratio was lower in HPV DNA-positive women than in controls (p=0.036). The difference was more pronounced in non-smoking women, in this group also the salivary MMP-8 levels differed (p=0.047). There was a correlation between the salivary concentrations of myeloperoxidase and MMP-8 (r=0.567, p<0.001) or MMP-9 (r=0.234, p=003), but no correlation between salivary and serum MMP-8 levels. The MMP-9 concentration and the MMP-9/TIMP-1 molar ratio were significantly lower in smokers than in non-smokers (p=0.020 and p=0.003, respectively). Persistent oral HPV infection was associated with a low salivary MMP-8 concentration indicating eventually a failure in oral anti-inflammatory defence.