Alterations of HPV-Related Biomarkers after Prophylactic HPV Vaccination. A Prospective Pilot Observational Study in Greek Women

George Valasoulis; Abraham Pouliakis; George Michail; Christine Kottaridi; Aris Spathis; Maria Kyrgiou; Evangelos Paraskevaidis; Alexandros Daponte

doi:10.3390/cancers12051164

Alterations of HPV-Related Biomarkers after Prophylactic HPV Vaccination. A Prospective Pilot Observational Study in Greek Women

Cancers (Basel). 2020 May 5;12(5):1164. doi: 10.3390/cancers12051164.

Authors

George Valasoulis^{1

2}, Abraham Pouliakis³, George Michail⁴, Christine Kottaridi³, Aris Spathis³, Maria Kyrgiou⁵, Evangelos Paraskevaidis⁶, Alexandros Daponte¹

Affiliations

¹ Department of Obstetrics & Gynaecology, University Hospital of Larisa, Mezourlo, 41334 Larisa, Greece.
² Hellenic National Public Health Organization-ECDC, Marousi, 15123 Athens, Greece.
³ Second Department of Pathology, Attikon University Hospital, National and Kapodistrian University of Athens, Chaidari, 12462 Athens, Greece.
⁴ Department of Obstetrics & Gynaecology, University Hospital of Patras, Rio, 26504 Patras, Greece.
⁵ West London Gynaecological Cancer Center, Department of Obstetrics & Gynaecology, Queen Charlotte's and Chelsea Hospital, Hammersmith Hospital, London W120HS, UK.
⁶ Department of Obstetrics & Gynaecology, University Hospital of Ioannina, Neochoropoulo, 45500 Ioannina, Greece.

Abstract

The objective of this study was to investigate the hypothesis that HPV vaccination administered in patients with low-grade (LG) cytology shortly after an initial colposcopic assessment could prospectively alter HPV-related biomarkers. This was a prospective pilot observational study involving women attending a colposcopy clinic for evaluation of abnormal LG cytology that were advised to undergo HPV vaccination and proceeded accordingly. These women were compared with a matched unvaccinated group. Women requiring cervical biopsies or CIN treatment were excluded.

Intervention: A full three-dose HPV vaccination was undertaken with either the 2-valent or the 4-valent anti-HPV VLP vaccine. LBC samples were obtained prior and after the completion of the vaccination regimen and tested for HPV DNA genotyping (CLART-2 HPV test) and E6 and E7 mRNA (NASBA technique).

Results: Alterations of HPV-related biomarkers at a colposcopy reassessment appointment 12 months later.

Analysis: The p-values, relative risk (RR), absolute relative risk (ARR), number needed to treat (NNT) and 95% confidence intervals for each biomarker in each group were assessed.

Results: A total of 309 women were included in the analysis. One hundred fifty-two women received the vaccine. HPV vaccination reduced in a statistically significant manner (p < 0.05) HPV DNA positivity rates for genotypes 16, 18, and 31, RR = 1.6 (95% CI: 1.1 to 2.3), RR = 1.7 (95% CI: 1.1 to 2.8), and RR = 1.8 (95% CI: 1.0 to 2.9), in women who only tested DNA-positive for HPV16, 18, and 31 genotypes, respectively, prior to vaccination. A less pronounced, statistically insignificant reduction was shown for women who tested positive for both HPV DNA and mRNA E6 and E7 expression for HPV16, 18, and 33 subtypes. Statistically significant reduction in HPV mRNA positivity was solely documented for genotype 31 (p = 0.0411).

Conclusions: HPV vaccination appears to significantly affect the rates of HPV16, 18, and 31 DNA-positive infections in the population testing HPV DNA-positive for the aforementioned genotypes. The above findings deserve verification in larger cohorts.

Keywords: HPV DNA genotyping; HPV mRNA E6 and E7; HPV vaccine; colposcopy clinic; persistent HPV infection; pilot study.