Association Study between Cervical Lesions and Single or Multiple Vaccine-Target and Non-Vaccine Target Human Papillomavirus (HPV) Types in Women from Northeastern Brazil.

Bárbara Simas Chagas,Manola Comar,Antonio Carlos De Freitas,Sergio Crovella,Sérgio Paiva,Ana Pavla Almeida Diniz Gurgel,Silva Seraceni,Maria Lina Tornesello

doi:10.1371/journal.pone.0132570

Abstract

We performed an association between high-grade squamous intraepithelial lesions (HSIL), low-grade squamous intraepithelial lesions (LSIL) and single or multiple vaccine-target as well as non-vaccine target Human papillomavirus (HPV) types. Using bead-based HPV genotyping, 594 gynecological samples were genotyped. An association between squamous intraepithelial lesion (SIL) and presence of HPV16, 18, 31, 58 and 56 types were calculated. The risk was estimated by using odds ratio (OR) and 95% of confidence intervals (CI). A total of 370 (62.3%) women were HPV positive. Among these, 157 (42.7%) presented a single HPV infection, and 212 (57.3%) were infected by more than one HPV type. HPV31 was the most prevalent genotype, regardless single and multiple HPV infections. Single infection with HPV31 was associated with LSIL (OR=2.32; 95%CI: 1.01 to 5.32; p=0.04); HPV31 was also associated with LSIL (OR=3.28; 95%CI: 1.74 to 6.19; p= 0.0002) and HSIL (OR=3.82; 95%CI: 2.10 to 6.97; p<0.001) in multiple HPV infections. Risk to harbor cervical lesions was observed in multiple HPV infections with regard to the HPV56 (OR=5.39; 95%CI: 2.44 to 11.90; p<0.001for LSIL; OR=5.37; 95%CI: 2.71 to 10.69; p<0.001) and HPV58 (OR=3.29; 95%CI: 1.34 to 8.09; p=0.0091 for LSIL; OR=3.55; 95%CI: 1.56 to 8.11; p=0.0026) genotypes. In addition, women coinfected with HPV16/31/56 types had 6 and 5-fold increased risk of HSIL (OR=6.46; 95%CI: 1.89 to 22.09; p=0.002) and LSIL (OR=5.22; 95%CI: 1.10 to 24.70; p=0.03), respectively. Multiple HPV infections without HPV16/18 has 2-fold increased risk of HSIL (OR=2.57; 95%CI: 1.41 to 4.70; p=0.002) and LSIL OR=2.03; 95%CI: 1.08 to 3.79; p=0.02). The results of this study suggest that single and multiple vaccine target as well as non-vaccine target HPV types are associated with LSIL and HSIL. These finding should be taken into consideration in the design of HPV vaccination strategies.

Highlights

Clinical and epidemiological studies report that cervical infection with High Risk Human papillomavirus (HR Human Papillomavirus (HPV)) is necessary but not sufficient to cause the development of cervical cancer [1,2]
Regarding women diagnosed with high squamous intraepithelial lesions (HSIL), HPV16, HPV31, HPV66, HPV35, HPV51, HPV52 and HPV56 were most commonly detected in single HPV infection, while HPV31/56 was the most frequent co-infections observed in this group (Fig 4A and 4B)
These findings suggest an association between the presence of HPV types and the risk to develop any squamous intraepithelial lesions (SIL) in women from Northeastern Brazil

Summary

Introduction

Clinical and epidemiological studies report that cervical infection with High Risk Human papillomavirus (HR HPV) is necessary but not sufficient to cause the development of cervical cancer [1,2]. Additional risk factors are likely to be involved in the development of cervical cancer, including multiple HPV infections [3]. Persistent infection with HR HPV is considered as the main cause of cervical lesions and cervical cancer [4]. The classification of HPV types is based on the intrinsic oncogenic potential of these viruses, where 15 oncogenic genotypes are associated with the majority of cervical lesions and cervical cancer [5]. The remainder 30% of cervical cancer rates are caused by other genotype target of 9-Valent HPV vaccine (HPV31, 33, 45, 52 and 58) as well as non-vaccine HPV types (NV HPV) (such as HPV26, 35, 39, 53, 56, 66, 68, 73) [7]

Methods

Results

Conclusion