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Genetic variability of human papillomavirus type 66 L1 gene among women presenting for cervical cancer screening in Chile

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Abstract

The high-risk human papillomaviruses (HR-HPVs) are involved in the development of cervical cancer. Nevertheless, there are differences in the oncogenic potential among them. HPV-16 and HPV-18 are associated with approximately 70% of cancer worldwide, and both types are the most extensively studied HR-HPV. Great variations in the prevalence of HR-HPV have been described in different countries. The impact of these variations on the epidemiology of lesions and cervical cancer is currently unknown. A high prevalence of HPV-66 has been detected in Chile. Here, we have analyzed the genetic variability of the L1 gene from HPV-66-infected Chilean women. Higher order interactions between identified mutations were analyzed by co-variation and cluster analyses. Antigenic-index alterations following L1 mutations and B-cell epitopes were predicted by BcePred algorithm. HPV-66 L1 sequences clustered phylogenetically into two main clades. The genetic variability in the HPV-66 L1 gene involved thirty nucleotide changes. Four of these were for the first time identified in this study. Some of these variants are embedded in the B-cell epitope regions. Amino acid homology in the immunodominant epitopes of HPV-66 L1 protein (DE, FG and H1 loops) was 42.9–59.1% and 28.6–68.9% compared with HPV-16 and HPV-18, respectively. The results of this research suggest that the neutralizing epitopes of HPV-66 are antigenically different compared to HPV-16 and HPV-18. Our findings show the need to perform new structural and immunological studies on HPV-66 L1 protein to evaluate the cross-protection conferred by current HPV vaccines.

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Acknowledgements

We thank Deyanira Vidal and Francisco Roldán for supporting the DNA purification and HPV typing assays; and Vivian Gómez and María Ibáñez for technical help with the sequencing of L1 gene.

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Authors and Affiliations

  1. Sección Virus Oncogénicos, Subdepto. de Enfermedades Virales, Instituto de Salud Pública de Chile, Avenida Marathon 1000, Ñuñoa, Santiago, Chile

    Monserrat Balanda, Nicolás Vergara, Héctor San Martín & Eugenio Ramírez

  2. Subdepto. de Genética Molecular, Instituto de Salud Pública de Chile, Avenida Marathon 1000, Ñuñoa, Santiago, Chile

    Jorge Fernández, Constanza Campano & Loredana Arata

  3. Dirección de Atención Primaria, Servicio de Salud Metropolitano Central, Santiago, Chile

    Nicolás Vergara

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  1. Monserrat Balanda
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Correspondence to Eugenio Ramírez.

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Ethical approval

Six public health care centers and their referral hospital participated in this study using the infrastructure, personnel and protocols already in place under the national cervical cancer prevention program. The study protocol was approved by the Ethics Committee of the Servicio de Salud Metropolitano Central.

Informed consent

Women were invited to participate through an outreach campaign in the catchment area of each health center and, if interested, received an appointment with the health center midwife. Eligible women who agreed to participate signed an informed consent form and entered the study.

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Balanda, M., Fernández, J., Vergara, N. et al. Genetic variability of human papillomavirus type 66 L1 gene among women presenting for cervical cancer screening in Chile. Med Microbiol Immunol 208, 757–771 (2019). https://doi.org/10.1007/s00430-019-00621-w

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