Prevalence of high-risk HPV genotypes, categorised by their quadrivalent and nine-valent HPV vaccination coverage, and the genotype association with high-grade lesions
Authors: Juan Carlos Rodríguez Díaz
Ma Encarnación Andrada Becerra
María Montserrat Ruiz García
Paula Parás-Bravo
Joaquín Portilla
José María Rodríguez Ingelmo
Miguel Santibañez
María Paz-Zulueta
Ledicia Álvarez-Paredes
Journal: BMC Cancer (2018)
Discipline: CLINICAL MEDICINE
Keywords: HPV vaccine; high-risk genotypes; high-grade lesions; prevalence; genotyping
Affiliations: Faculty of Nursing, University of Cantabria, Avda Valdecilla s/n. C.P.: 39008, Cantabria, Spain. ., Department of Microbiology and Parasitology, University Hospital of Burgos, C/ Islas Baleares, 3 - C.P.: 09006, Burgos, Spain., Department of Microbiology, University General Hospital of Alicante. Pintor Baeza, 11- C.P.: 03010, Alicante, Spain., Faculty of Nursing, University of Cantabria, Avda Valdecilla s/n. C.P.: 39008, Cantabria, Spain., Department of Pathological Anatomy, University General Hospital of Elche. Camí de l'Almazara, 11 - C.P.: 03203, Alicante, Spain., Department of Gynecology, University General Hospital of Elche. Camí de l'Almazara, 11 - C.P.: 03203, Alicante, Spain., Department of Microbiology, University General Hospital of Elche. Camí de l'Almazara, 11 - C.P.: 03203, Alicante, Spain., Department of Infectious Diseases, University Hospital of Alicante. Pintor Baeza, 11- C.P.: 03010, Alicante, Spain.

Abstract:  Background: The new nine-valent vaccine against human papillomavirus (HPV) includes the four HPV genotypes (6, 11, 16, and 18) that are targeted by the older quadrivalent HPV vaccine, plus five additional oncogenic types (31, 33, 45, 52, and 58) remain significantly associated with high grade lesions. We aimed to determine the prevalence of high-risk HPV genotypes in unvaccinated subjects and the association of these genotypes with the incidence of high-grade lesions. We also assessed which, if either, of these two HPV vaccines could have prevented these cases. Methods: This cross-sectional study, conducted from 4 January 2010 to 30 December 2011, was composed of 595 women attending the Hospital General Universitario de Elche (Spain) gynaecology department who were positively screened for opportunistic cervical cancer by pap smears and HPV detection during a routine gynaecological health check. The pap smear results were classified using the Bethesda system. HPV genotyping was performed with the Linear Array HPV genotyping test, and viruses were classified by the International Agency for Research on Cancer assessment of HPV carcinogenicity. Odds ratios (ORs) with their 95% confidence intervals (95% CI) were estimated by logistic regression, adjusting for age and immigrant status. The prevented fraction among those exposed (PFe-adjusted) was determined as a measure of impact. Results: At least one of the additional five high-risk HPV genotypes present in the nine-valent HPV vaccine was detected in 20.5% of subjects. After excluding women with genotype 16 and/or 18 co-infection, high-risk genotypes (31, 33, 45, 52, and 58) were associated with a higher risk of intraepithelial lesion or malignancy: adjusted OR = 3.51 (95% CI, 1.29-9.56), PFe-adjusted = 0.72 (95% CI, 0.22-0.90). Genotypes that are still non-vaccine-targeted were detected in 17.98% of the women, but these were not significantly associated with high-grade lesions. Conclusion: The greater protection of the nine-valent HPV vaccine is likely to have a positive impact because, in the absence of genotype 16 or 18 infection, these five genotypes on their own remained significantly associated with high-grade lesions. 

Retracted: No

PubPeer comments:
 The patient population and outcome measurements in this paper is surprisingly similar to that in an older paper with this author as a co-author. The older paper is: Magdy R. Ahmed et al., The Journal of Maternal-Fetal Neonatal Medicine (2016), DOI: 10.1080 14767058.2016.1219996, published online in August 2016. The 2016 paper describes a group of a group of 218 pregnant women recruited at the Obstetrics and Gynecology department of **Suez Canal University Hospitals**, Ismailia, Egypt. This newer paper (received September 2018) describes a group of 226 pregnant women recruited at the Obstetrics and Gynecology department of **King Abd AL-Aziz Hospital,** Jeddah, KSA. Comparing these two papers, the values in **Table 1** are unexpectedly similar, either identical or differing often only in one digit. The p values showing both groups are not statistically different in maternal characteristics are identical. I have highlighted similar values with boxes of the same color. ![file] This problem was brought to my attention by Twitter user @BWMol. , 
 In **Table 2**, although the absolute and relative numbers of patients are different between the two studies, the p values, relative risk, and confidence intervals are surprisingly identical. ![file] This is even more surprising, given that in the 2016 study performed in Egypt, the vaginal cleaning was done  *with three 10 X 10 cm sterile gauze pieces of chlorhexidine acetate 0.25%* , while in the Saudi Arabia 2019 paper, the cleaning was done  *with two sterile gauze pieces of povidone-iodine solution 10%* . Can the authors please clarify how two different studies performed in two different countries could yield exactly the same statistical findings and relative risks? ,