Several studies have documented that the prevalence of HPV among pregnant women was at least 30%. Studies on vertical transmission of HPV estimate that the risk of HPV-positive women transmitting HPV to their children is about 10%. Despite evidence of the detection of HPV in children born to HPV-positive mothers, risk factors associated with vertical transmission are not well documented.

In January 2025, a research team from the University of Montreal, Canada, published important research findings in the Journal of Medical Virology (IF: 6.8).The findings suggest that, although HPV viral load generally decreases during pregnancy, vertical transmission was strongly associated with high HPV viral load. Although, the detailed biological mechanism by which viral load is linked to vertical transmission remains to be explained, it may serve as a biomarker for the risk of vertical transmission.

Methods

Briefly, 1050 pregnant women were recruited between 2010 and 2016 in outpatient obstetric clinics catering to the local community at three academic health centres in Montreal, Canada. Women aged 18 and above, without HIV infection, and in their first trimester of pregnancy (between 6 and 14 weeks of gestation) were eligible. This study included 287 mothers who tested positive for the 13 most common HPV genotypes during pregnancy including HPV 6, 11, 16, 18, 31, 33, 39, 42, 45, 51, 52, 58, and 89. In the first and third trimester (32–35 weeks of gestation), a self-collected vaginal swab was provided from the mothers for HPV DNA testing. After birth, swabs were also collected for the purpose of HPV DNA testing. Four sites were sampled in children (conjunctival, oral, pharyngeal, and genital) at birth (after 24 to 48 h) and/or at 3 months of age for HPV DNA testing.

FIGURE 1 | Study flow diagram of the cohort population included in the study. HPV, Human papillomavirus; HERITAGE: Human Papillomavirus (HPV) perinatal transmission and risk of HPV persistence among children.

Results

Finding1:

287 mothers were infected with at least one of the genotypes evaluated for viral load quantification (HPV‐6, 11, 16, 18, 31, 33, 39, 42, 45, 51, 52, 58, and 89). Table 2 provides a description of the viral loads detected for these children and their mother. HPV16 was detected in 3 of these children (6.4%: 95% CI: 2.0–18.5) who were born out of the 47 mothers positive for HPV‐16 during their pregnancy. It is important to note that two children have been found with genotype that were not present in the mother during pregnancy.

TABLE 2 | HPV viral load for the 15 children in whom HPV was detected during the perinatal period and their mothers.

Finding2:

Overall, mean and median HPV viral loads were lower in the third trimester compared to the first trimester of pregnancy; the mean difference was −0.0492 copies/cell (mean difference =1.0366−1.0858) and the median difference was −0.0001 copies/

cell (median difference = 0.0007−0.0008). Among women with persistent infection, we observed a decrease in viral load detected at third trimester compared to the first trimester for most genotypes that was statistically significant for all genotypes taken together (decreases in the median viral load of −0.0002 copies/cell, p‐value: 0.0186). Interestingly, the decreases in median viral load considering all infections were mostly explained by genotype present in single infection (−0.0005 copies/cell, p‐value: 0.0024) rather than in multiple infections (> −0.0001 copies/cell, p‐value = 0.8027). A statistically significant difference was also observed specifically for HPV‐16 (median difference = −0.0100, p‐value: 0.0478).

TABLE 3 | HPV viral load measures in mothers during pregnancy and in children during the perinatal period.

Finding3:

Figure 2 illustrates the variation in viral load measured throughout trimesters where each line represents a genotype-specific HPV episode detected in each mother from which we can observe the tendency toward a reduction of viral load from the first to the third trimester. Overall, viral load was significantly lower in the 15 children with perinatal HPV compared to their respective mothers. Considering all genotypes detected, the median difference in viral load between children and mother was of −0.4249 copies/cell (p‐value: 0.0038).

FIGURE 2 | Variation in viral load of specific HPV genotypes between the first and the third trimester of pregnancy.

Finding4:

The measures of association between genotype-specific HPV viral load during pregnancy and vertical transmission are presented in Table 4. For any genotypes and for HPV-16 detected in the first trimester, each unit increase of viral load was associated with an increased risk of vertical transmission of 5% (aOR [95% CI]: 1.05 [1.00–1.09]) and of 14% (aOR [95% CI]: 1.14 [1.00–1.29]), respectively. The same trend was observed when considering the third and both trimesters combined. For any genotypes and for HPV-16 detected at first trimester, women with more than two copies per cell had a significantly higher risk of vertical transmission compared to women with two copies per cell or less (aORs = 6.41 [95% CI: 1.10–37.34] for any genotypes and 17.17 [95% CI: 1.18–250.28] for HPV-16). The risk of transmission among women who had an increase in viral load between third and first trimester was higher than among those who had a decrease or similar viral load between third and first trimester (aORs = 4.51 [95% CI: 0.41–49.11] for all genotypes combined and 42.45 [95% CI: 0.89–2030.79] for HPV-16, data not shown).

TABLE 4 | Association between viral load during pregnancy and vertical transmission

Reference:

- Bénard E A, Carceller A M, Mayrand M H, et al. Viral Load of Human Papillomavirus (HPV) During Pregnancy and Its Association With HPV Vertical Transmission[J]. Journal of Medical Virology, 2025, 97(2): e70221.