Introduction

Cervical cancer is the cancer of the cervix, the lower part of the uterus that connects to the vagina. Although the exact cause of cervical cancer has not been elucidated, the role of Human Papilloma Virus (HPV) in the oncogenesis has been established. Multiple sexual partnerships, sexual activity before eighteen years of age and infection with sexually transmitted pathogens enhance the risk of cervical cancer by increasing the chance of HPV infection. A compromised immune system and smoking are known risk factors (Netzer et.al, 2013). The symptoms of cervical cancer appear only in the advanced stages of the disease and include vaginal bleeding after intercourse, vaginal bleeding between periods, and vaginal bleeding after menopause, vaginal discharge with a foul odor, pelvic pain and abnormal pain during intercourse. Cervical cancer is classified as Squamous cell carcinoma and Adenocarcinoma. Squamous cell carcinomas have their origin in squamous cells that line the bottom of the cervix and Adenocarcinomas have their origin in the glandular cells that line the cervical canal (Garces et.al, 2013). Screening protocol for cervical cancer includes Pap test and HPV DNA test. Diagnostic protocol includes colposcopic examination of the cervix and cone biopsy. Further staging of the cancer is done by cystoscopic and proctoscopic visual examinations, CT and MRI. In Stage I the cancer is confined to cervix. In Stage II both cervix and uterus are affected. In Stage III, the pelvic wall and lower parts of the vagina also get affected and in Stage IV, the cancer spreads to bladder, rectum and other organs. Surgical treatment in early stages is done by simple hysterectomy. Radical hysterectomy is the option in advanced stages. Radiation protocol includes external radiation and brachytherapy. Chemotherapy is effective in advanced stages. FDA has approved two HPV vaccines for prevention of cervical cancer.

Updates on Manifestation

It is a fact that cervical cancer spreads through the lymphatic system. It is also a fact that specific type of cells called the ‘Tumor-Associated Lymphatic Endothelial Cells’ are involved in oncogenesis of certain cancers. A recent study to isolate ‘Tumor-Associated Lymphatic Endothelial Cells’ from human cervical cancers and investigate their role in the oncogenesis of cervical cancer has shown that ‘Tumor-Associated Lymphatic Endothelial Cells’ promote lymphatic metastasis of cervical cancer (Cai et.al, 2013). Recently, a RNA polymerase II subunit RPB5-associated protein known to play a role in the progression of certain types of cancers has been found to be actively associated with the squamous cell carcinoma of the cervix. It has also been shown that the protein expression is evident not only in cervical cancers but also in cervical intra-epithelial neoplasias. Since the risk of cervical intra-epithelial neoplasias turning into cervical cancer is high, the role of this URI/RMP protein in the oncogenesis of cervical cancer is significant and demands attention (Gu et.al, 2013). Studies have also elucidated the role of Epidermal Growth Factor (EGF) in cervical cancer cell proliferation. The epidermal growth factor acts in the dysregulation of certain sub-pathways in the mitogen-activated protein kinase signaling pathway and p53 signaling pathway (Ai et.al, 2013). Bone metastases of the lumbar spine and pelvic bones are known manifestations in cervical cancer recurrence. A rare manifestation of cervical cancer recurrence presenting as a painful jaw swelling due to metastasis to the mandibular condyle has been recently reported (Puranik et.al, 2013).

Updates on Screening

Disease recurrences continue to be a major problem in cervical cancer. F-fluorodeoxyglucose (FDG) positron emission tomography - computed tomography (PET/CT) has gained prominence in the investigation of cervical cancer due its clarity on imaging modalities for lymph node status and distant metastasis. It is now possible to determine PET-defined cervical tumor volume that predicts overall survival. FDG-PET is also employed to assess the treatment response after completing concurrent chemo-radiotherapy (CRT) and in suspected disease recurrence. It is imperative to note that defining and demarcating disease areas is critical to avoid irradiating normal tissues in image-guided adaptive radiotherapy. FDG-PET can be utilized in radiation therapy, where, treatment volumes can be adjusted and higher radiation doses safely delivered to FDG-positive lymph nodes. FDG-PET/CT has been useful in image-guided brachytherapy as well. Attempts are underway to employ molecular imaging tracers to identify aggressive tumors. A Cu-labeled diacetyl-di N (4)-methylthiosemicarbazone that is absorbed by hypoxic tissues has been shown to be a valuable tool in predicting the treatment modalities (Herrera et.al, 2013). A prototype clinical decision support system (CDSS) for cervical cancer screening has also been developed and evaluated based on multiple guidelines and free-text processing. The CDSS prototype has about eighty seven percent accuracy on screening decisions (Wagholikar et.al, 2013).

Therapeutic Updates

Gene therapy for recurrent cervical cancer has been a priority in cancer research. Delivery of the therapeutic genes into the cancer cells has been a critical challenge. A novel TPGS-b-(PCL-ran-PGA) nanoparticle modified with polyethyleneimine to be utilized as a vector of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and endostatin for cervical cancer gene therapy is being investigated. Research data shows that these nanoparticles could be effectively employed to deliver plasmids into HeLa cells and significantly increase the cytotoxicity. It has also been shown that the combined use of TPGS with TRAIL and endostatin can compound the antitumor activity for in vivo cancer gene delivery (Zheng, et.al, 2013). Three-Dimensional Image-Guided Brachytherapy (IGABT) has been another useful tool in the treatment of cervical cancer. Studies to evaluate the IGABT outcomes after concomitant chemoradiation (CCRT) has shown that IGABT combined with CCRT provides excellent locoregional control rates with low treatment-related morbidity (Mazeron et.al, 2013). Intraoperative Electron Beam Radiotherapy (IOERT) has also been successfully employed for the treatment of recurrent or advanced cervical cancer. Studies to evaluate the treatment outcomes of IOERT have shown that combined modality therapy including IOERT for advanced cervical cancer improves survival chances (Barney et.al, 2013).

Conclusion

Cervical cancer is one of the leading causes of death in women (Netzer et.al, 2013). The role of Human Papilloma Virus (HPV) in the oncogenesis of cervical cancer has been established. Prompt cervical cancer screening by Papanicolaou Smear and Human Papillomavirus Vaccination has significantly reduced the morbidity and mortality of the disease (Drolet et.al, 2013). Further, advanced screening protocols like PET/CT and CDSS supported by therapeutic innovations like Intraoperative Electron Beam Radiotherapy (IOERT), Three-Dimensional Image-Guided Brachytherapy (IGABT) and Gene therapy ensure better cancer care and survival chances.

Reference

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