Abstract A20: Persistent high-risk HPV infection in the development of uterine cervical cancer
Authors: Pablo Moreno Acosta, Diana Mayorga, Nicolas Magné
Journal: Cancer Research (2020)

Abstract The early detection and treatment of preneoplastic uterine cervical lesions is certainly a major challenge for developing countries. Preneoplastic lesions result from human papilloma virus (HPV) infection in cells located in the transformation zone of the cervical epithelial tissue, causing low-grade or high-grade lesions. HPV infections are transient and most of the time cleared within a couple of years following exposure. However, 10–20% of infections persist latently, leading to disease progression and, ultimately, various forms of invasive cancer. The transformation of preneoplastic lesions in invasive cancer cells is provoked at least partly by HPV, especially through gene and protein expression modulation. This modulation involves tissue oxygenation, oncogene activation, loss of tumor suppressor genes and aberrant molecular signaling pathways (such as Insulin-like growth factor-1 receptor (IGF-1R). In recent studies, it was reported that IGF1R is overexpressed by effect of E6 AA-a and E-G350 HPV-16 variants. The aim of the present study was to prospectively and retrospectively report the detection of HPV-16 variants and IGF1R expression in patients with cervical cancer and assess the relationship with development of uterine cervical cancer. Sixty consecutive patients with invasive cervical cancer were assessed for HPV-16. A total of 35 patients (58.3%) were infected with HPV-16, with a mean age of 51 years (range: 30–76 years). Thirty patients (85.7%) were diagnosed with European HPV-16 variant and five patients (14.3%) were diagnosed with non-European HPV-16 variants. European HPV-16 variants (E-HPV-16) were mainly E-G350 (n = 14; 41.1%) and E-T350 (n = 12; 35.2%) subclasses. Of these 35 patients, 15 received exclusive radiotherapy and four radiochemotherapy, and the remaining 16 did not complete the treatment (NCT). Of the patients who presented an incomplete response, overexpression of IGF1R was detected in all. Of patients NCT, we retrospectively studied one case in IIIB stage FIGO. Samples of preneoplastic lesions and invasive cervical cancer were analyzed to confirm histopathologic diagnosis and detect the presence of HPV variants and overexpression of IGF-1R. Of the results found in this case, in which the patient was diagnosed in 1986 with a high-grade squamous intraepithelial cervical lesion, HPV-16 E-G350 and HPV-33 coinfection as low expression of IGF1R were detected and for the invasive cancer diagnosed in 2002, the presence of HPV-16 AA-c and overexpression of IGF1R was detected. The detection of high-risk HPV in samples of preneoplastic lesions and invasive cancer in a 60-year-old patient at the time of diagnosis showed that HPV33 infection was eliminated. Results such as these suggest that persistent infection with HPV-16 variants, overexpression of IGF1R, such as viral load and age, could be necessary factors for disease progression, and thus contribute to the identification of patients with a high risk of viral persistence and development of cervical neoplasia. Note: This abstract was not presented at the conference. Citation Format: Pablo Moreno Acosta, Diana Mayorga, Nicolas Magné. Persistent high-risk HPV infection in the development of uterine cervical cancer [abstract]. In: Proceedings of the AACR Special Conference on the Microbiome, Viruses, and Cancer; 2020 Feb 21-24; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2020;80(8 Suppl):Abstract nr A20.