Comparison of the vaginal microbiota diversity of women with and without human papillomavirus infection: a cross-sectional study

Abstract

Background: The female genital tract is an important bacterial habitat of the human body, and vaginal microbiota plays a crucial role in vaginal health. The alteration of vaginal microbiota affects millions of women annually, and is associated with numerous adverse health outcomes, including human papillomavirus (HPV) infection. However, previous studies have primarily focused on the association between bacterial vaginosis and HPV infection. Little is known about the composition of vaginal microbial communities involved in HPV acquisition. The present study was performed to investigate whether HPV infection was associated with the diversity and composition of vaginal microbiota.

Methods: A total of 70 healthy women (32 HPV-negative and 38 HPV-positive) with normal cervical cytology were enrolled in this study. Culture-independent polymerase chain reaction-denaturing gradient gel electrophoresis was used to measure the diversity and composition of vaginal microbiota of all subjects.

Results: We found significantly greater biological diversity in the vaginal microbiota of HPV-positive women (p < 0.001). Lactobacillus, including L. gallinarum, L. iners and L. gasseri, was the predominant genus and was detected in all women. No significant difference between HPV-positive and HPV-negative women was found for the frequency of detection of L. gallinarum (p = 0.775) or L. iners (p = 0.717), but L. gasseri was found at a significantly higher frequency in HPV-positive women (p = 0.005). Gardnerella vaginalis was also found at a significantly higher frequency in HPV-positive women (p = 0.031). Dendrograms revealed that vaginal microbiota from the two groups had different profiles.

Conclusions: Our study is the first systematic evaluation of an association between vaginal microbiota and HPV infection, and we have demonstrated that compared with HPV-negative women, the bacterial diversity of HPV-positive women is more complex and the composition of vaginal microbiota is different.

Figure 1

PCR-DGGE profiles of the predominant bacterial communities in vaginal swabs from five HPV-negative women (left: N1–N5) and five HPV-positive women (right: H1–H5). Lane M is a marker constructed in this study with the identified bands to facilitate the interpretation of the figure. Bands: a: Lactobacillus fabifermentans strain, LMG 24284 16S ribosomal RNA; b: Gemella haemolysans strain, ATCC 10379 16S ribosomal RNA; c: Staphylococcus warneri strain, AW 25 16S ribosomal RNA; d: Streptococcus mutans strain, ATCC 25175 16S ribosomal RNA; e: Streptococcus sobrinus strain, ATCC 33478 16S ribosomal RNA; f: Escherichia fergusonii, ATCC 35469 16S ribosomal RNA; g: Actinomyces graevenitzii strain, CCUG 27294 16S ribosomal RNA; h: Actinomyces turicensis strain, APL10 16S ribosomal RNA; i: Actinomyces viscosus strain, NCTC 10951 16S ribosomal RNA; j: Actinomyces israelii strain, CIP 103259 16S ribosomal RNA. The bilateral part of the figure shows the marker files from different DGGE gels. Each peak in the files stands for one marker. A pairwise analysis, using Gel Compare® software, of the gel marker in each gel indicated that the marginal discrepancies of markers between each gel were negligible.

Figure 2

Mann–Whitney U test of the Shannon-Weiner diversity indices from HPV-negative women and HPV-positive women.

Figure 3

Hierarchical cluster analysis and discriminative characters analysis of all DGGE profiles. HPV-negative women are green and HPV-positive women are red. The box around bands A is green, the box around bands B is red, and the box around bands C is blue.