Chlamydia trachomatis and human papillomavirus coinfection: association with p16INK4a and Ki67 expression in biopsies of patients with pre-neoplastic and neoplastic lesions

Abstract

The objective of this study was to identify the frequency of coinfection by human papillomavirus (HPV) and Chlamydia trachomatis (CT) in cervical lesions and relate it with immunohistochemical expression of p16INK4a and Ki67, both oncogenicity markers. A cross-sectional study with 86 women from primary care units in southern Brazil was conducted. Cervical swabs were collected for HPV-DNA and CT-DNA detection, through the polymerase chain reaction technique (PCR). The immunohistochemical analysis was performed on biopsy cervical tissue material to identify the expression of p16INK4a and Ki67 cell cycle markers. About 83 % were positive for HPV-DNA and 19% had coinfection with CT-DNA. Among coinfected women, 56% expressed p16INK4a. There was a statistically significant association between the histological grade of the lesion and Ki67 expression. All high-grade lesions, 50% of low-grade lesions and 31% of negative biopsies expressed Ki67 (p = 0.004). A total of 37% of coinfected women expressed both markers. In conclusion, although more than half of the coinfected patients have expressed p16INK4a and more than one third have expressed both markers, these results suggest no association between those variables. However, other studies involving larger samples are necessary to corroborate such findings. Keywords: epidemiology; human papillomavirus 16; biomarkers; pharmacological. Each year, approximately 493,000 new cases of cervical cancer are diagnosed worldwide and approximately 273,000 women die from the disease, making it the second most frequent cancer in women and the second leading cause of cancer-related death worldwide among women 15 to 44 years old. 1Chlamydia trachomatis (CT) is the most common bacterial sexually transmitted infection (STI) worldwide.2 Bacterial coinfection by CT in women with a history of HPV infection has been studied as a potential factor that contributes to the development of malignacies and cervical cancer. Some authors 3 have suggested that previous CT infection is associated with a high risk of developing the disease.The p16INK4a is a cyclin-dependent kinase inhibitor (CDK) that reduces the cell cycle's speed by controlling the expression of E2F transcription factor. High-grade infection by HPV is involved in the carcinogenesis and, HPV integration in the human genome results in overexpression of E6 and E7 viral oncoproteins.4 E7 HPV protein interacts with retinoblastoma protein (pRb) and neutralizes the function of these proteins, resulting in the release of E2F transcription factor of the pRb-E2F complex. E2F accumulation induces p16INK4a activity. 5Results of a study 6 showed that none of the negative cervical tissues were positive for p16INK4a, while there was a constant and significant increase in the positivity of this marker, according to histological grade, where cervical intraepithelial neoplasia (CIN) 1 had 31% positivity, 90% in CIN 2 and 100% in CIN 3 and carcinomas (p < 0.0001). Thus, p16INK4a overexpression has consistently shown high sensitivity (84%) and speci...

Chlamydia trachomatis Co-infection in HPV Positive Women brings no Additional Risk of High-grade Cervical Intraepithelial Neoplasia

“…Human papillomavirus (HPV), a sexually transmitted deoxyribonucleic acid (DNA) virus, is widely accepted as the cause of cervical cancer [1]. HPV and Chlamydia trachomatis (CT) cause most common sexually transmitted transmitted infections worldwide [2][3][4]. The prevalence of both infections is higher in young women [5,6] and factors that are associated with its acquisition are also shared [7].…”