Abstract
Infection by an oncogenic human papillomavirus (HPV), in particular HPV16 and 18, is a high risk factor for developing cervical cancer; however, viral infection alone is not sufficient for cancer progression. Autophagy is hypothesized to be an important process during carcinogenesis. The aim of the present study was to investigate the association between autophagy and high-risk HPV (hrHPV) infection in human cervical squamous cell carcinomas (SCCs), and to analyze the clinical significance of this association. Quantum dot (QD)-based immunofluorescence histochemistry was used to detect the expression of autophagy markers, Beclin-1 and microtubule-associated proteins 1A/1B light chain 3B (LC3B) proteins, in 104 cases of cervical cancer (including 80 SCCs and 24 adenocarcinomas) and 20 normal cervical tissues. hrHPV (HPV16/18) infection was detected by QDs based fluorescence in situ hybridization in cervical cancers. The results revealed that the expression levels of Beclin-1 and LC3B were significantly lower in cervical cancer cells when compared with those of normal cervical squamous epithelial cells, and were found to negatively correlate with hrHPV infection. The expression levels of Beclin-1 and LC3B were not associated with age, tumor grade, tumor stage, tumor node metastasis stage or lymph node metastasis. However, a positive correlation was identified between Beclin-1 and LC3B protein expression. In addition, the absence of autophagy in combination with hrHPV infection may accelerate the progression of cervical SCC. In conclusion, decreased expression of Beclin-1 and LC3B may be important in cervical carcinogenesis. The hrHPV-host cell interaction may inhibit autophagy, which may aid virus duplication and infection, as well as cervical cancer development.
Highlights
Cervical cancer is a leading cause of morbidity and mortality in females worldwide [1,2], and remains the most common type of gynecological malignant tumor in China [3]
A positive correlation was identified between Beclin‐1 and light chain 3B (LC3B) protein expression
The current study revealed that the expression levels of Beclin‐1 and LC3B are significantly lower in cervical cancer tissues than in normal cervical squamous epithelial tissues, and were found to negatively correlate with high‐risk HPV (hrHPV) infection
Summary
Cervical cancer is a leading cause of morbidity and mortality in females worldwide [1,2], and remains the most common type of gynecological malignant tumor in China [3]. Infection by an oncogenic human papillomavirus (HPV), in particular high‐risk HPV (hrHPV) types 16 and 18, is a risk factor for developing cervical cancer [4]. HPV is a double‐stranded DNA virus, which infects cutaneous and mucosal epithelial cells of the human body. HPV genomes consist of early, late, upstream regulatory and non‐coding regions. These viruses usually clear in 70‐90% of HPV infected individuals. HPV is the major causative agent of cervical cancer, the viral infection alone is not sufficient for cancer progression [5]. Investigating the underlying cellular and molecular mechanisms in cervical carcinogenesis is a key aim of studies worldwide in the vaccine era
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