By Renu Agrawal
Abnormal growth of cells in the cervix region which spread to the other parts of the body causes cervical cancer. Initially, no signs are found. However, as the final stages appear, abnormal vaginal bleeding or pelvic pain or pain during sexual intercourse is observed. It develops from precancerous changes which take over 10 to 20 years. In 2012, an estimated 528,000 cases of cervical cancer occurred, with 266,000 deaths around the globe.
Causes: Human papilloma virus types 16 and 18 are the main cause of 75% of cervical cancer cases globally. It is also caused by Cigarette smoking, both active and passive, long-term use of oral contraceptives and having many pregnancies. These are all associated with an increased risk of cervical cancer.
Symptoms: Symptoms of advanced cervical cancer may include: loss of appetite, weight loss, fatigue, pelvic pain, back pain, leg pain, swollen legs, heavy vaginal bleeding, bone fractures and sometimes, leakage of urine or faeces from the vagina. Bleeding after douching or after a pelvic examination is a common symptom of cervical cancer.
Diagnosis: For diagnosis, usually pep test is done. However, many times it is not reliable. Though squamous cell carcinoma is cervical cancer with the most incidences, the incidence of adenocarcinoma of the cervix has been increasing in recent decades. The common cervical carcinoma includes; Squamous cell carcinoma (about 80–85%, adenocarcinoma (about 15% of cervical cancers in the UK, adenosquamous carcinoma, mall cell carcinoma, neuroendocrine tumour, glassy cell carcinoma, villoglandular adenocarcinoma. Noncarcinoma malignancies which can rarely occur in the cervix include melanoma and lymphoma.
In invasive melanoma, usually, the survival of 89–95% is found where there is no tumour formation or the tumour formation is less than one mm. In the second stage, the tumour increases in size up to 4 mm with or without ulceration. In the next, third stage, there can be regional or distant metastasis with tumour formation. As the tumour formation happens with the UV radiation, these can be minimised by not going in the sun for a long time and by avoiding the UV nail lamps which are usually used to dry the nail polish.
However, as the body needs UV light to generate vitamin D, there is a need to balance in getting enough sunlight to maintain healthy vitamin D levels and by reducing the risk of melanoma caused due to UV radiations. It takes around half an hour of sunlight for the body to generate its vitamin D for the day and this is about the same amount of time for fair-skinned people to get a sunburn. Therefore, to protect oneself, exposure to sunlight can be intermittent instead of all at one time. Sunscreen appears to be an effective way in the prevention of melanoma. In the past, the use of sunscreens with a sun protection factor (SPF) of 50 or higher have been found to be effective.
Prevention and treatment: Treatment with statin and fibrate have been found beneficial. A method known as lymphoscintigraphy is performed in which a radioactive tracer is injected at the tumour site to localise the sentinel node(s). Further precision is provided using a blue tracer dye and surgery is performed to get a biopsy of the node(s). Routine hematoxylin and eosin (H&E) and immunoperoxidase staining have been found to be adequate to rule out node involvement. Polymerase chain reaction (PCR) tests on the nodes are usually performed to test many patients even with a negative sentinel lymph node. These actually have a small number of positive cells in their nodes. Another method is the use of a fine-needle aspiration biopsy to test masses.
The use of interferon is not recommended as a standard adjuvant treatment for melanoma. Metastatic melanomas can be detected by X-rays, CT scans, MRIs, PET and PET/CTs, ultrasound, LDH testing and photoacoustic detection. Chemotherapy drugs such as Dacarbazine have been the backbone of metastatic melanoma treatment since FDA approval in 1975. However, its efficacy. many a time cannot be assured as the melanoma cells may undergo mutations which may allow them to survive and grow indefinitely in the body. Small-molecule targeted therapies work by blocking the genes involved in pathways for tumour proliferation and survival.
The main treatments are BRAF, C-Kit and NRAS inhibitors. These inhibitors work to inhibit the downstream pathways involved in cell proliferation and tumour development due to the specific gene mutations. Immunotherapy is aimed at stimulating the person’s immune system against the tumour, by enhancing the body’s own ability to recognize and kill cancer cells. One immune checkpoint inhibitor treatment of pembrolizumab costs $10,000 to $12,000 USD for a single dose.
Usually, this has to be administered every 3 weeks. Cytokine therapies used for melanoma include IFN-a and IL-2. Immune checkpoint inhibitors include anti-CTLA-4 monoclonal antibodies (ipilimumab and tremelimumab), toll-like receptor (TLR) agonists, CD40 agonists, anti-PD-1 (pembrolizumab, pidilizumab, and nivolumab) and PD-L1 antibodies. Evidence suggests that anti-PD-1 antibodies are more effective than anti-CTLA4 antibodies with less systemic toxicity. Treatment is also done by surgically excising cancer and then treating the area with Aldara cream postoperatively for three months. While some studies have suggested the adjuvant use of topical tazarotene, the current evidence is not enough to recommend it. When melanomas get spread to the lymph nodes, then, an important factor is to know the number of nodes with malignancy. The extent of malignancy within a node is also important and only after examination of these critical points the treatment can be given.
(The writer is ex-chief scientist, CFTRI)