Disparities in screening, treatment, and survival exist in the absence of a national screening programme

Cervical cancer, caused mainly by Human Papillomavirus (HPV) infection, is leading cancer in Indian women and the second most common cancer in women worldwide.

Every year in India, 122,844 women are diagnosed with this type of cancer, and 67,477 die from the disease, which accounts for nearly one-third of the global cervical cancer toll. Indian women face a 2.5 percent cumulative lifetime risk and 1.4 percent cumulative death risk from the disease. At any given time, about 6.6 percent of women in the general population are estimated to harbor cervical HPV infection. HPV serotypes 16 and 18 accounts for nearly 76.7 percent of cervical cancer in India. .

Approximately every 47 minutes, a woman is diagnosed with cervical cancer. The risk factors for persistence and precancer are still not completely clear.

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What is cervical cancer?

Cervical cancer arises from Cervix due to abnormal cell growth, which invades or spreads to other parts of the body. Early on, typically no symptoms are seen. Later symptoms may include abnormal vaginal bleeding and pelvic pain. The progression of the disease has the stages of mild dysplasia as CIN1, a precancerous lesion affecting cervix, moderate dysplasia as CIN2, severe dysplasia as CIN3 and cervical cancer. The lag time between HPV infection and the appearance of the first microscopic evidence of pre-cancer is of prime importance. Cervical cancer is the second most common cancer and cause of death among women in developing countries. 86 percent of all deaths due to cervical cancer are in developing, low- and middle-income countries.

Viral risk factors

The cervical cancer has many strains but HPV genotype 16 and 18 are mainly responsible. Most men and women who are sexually active have been exposed to HPV. Over 85 percent of men and women have been infected with HPV at some time in their lives, Most infections clear up on their own. Some types of HPV can cause changes to cells in the cervix. If these changes are diagnosed early, cervical cancer can be prevented by removing or killing the changed cells before they can become cancer cells.

Non-HPV risk factors include several sexual partners, mutagens, smoking, co-infection with Chlamydia trachomatis or herpes simplex virus, hormones, immunosuppression, genetic predisposition and lack of awareness.

Disparity in screening, treatment, and survival exists in the absence of a national screening programme. An analysis of population-based surveys indicates that coverage of cervical cancer screening in developing countries is 19 percent compared to 63 percent in developed countries. The older and poor women who are at the highest risk of developing cancer are the least likely to undergo screening.

Opportunistic screening in various regions of India varies from 6.9 percent in Kerala to 0.006 percent and 0.002 percent in the western state of Maharashtra and southern state of Tamil Nadu, respectively. Cervical cancer diagnosis and treatment in the advanced stages make it a costly exercise, with a poor prognosis resulting in poor compliance. Five-year survival rates in Mumbai population-based cancer registry in 1992–1994 were 47.7 percent for cervical cancer. Survival was determined by age and the extent of disease, with younger women having longer survival.

HPV is a non-enveloped dsDNA virus with a circular genome of ~8 kb and is associated with warts and papillomas. There are more than 100 known genotypes of which 80 are fully sequenced. Types are assigned a sequential number based on order of discovery and E6 and E7 are the primary HPV oncoproteins, consistently expressed at low levels during the infectious process.

Progress in biotechnology has led to the development of many molecular diagnostic tests for cervical cancer. A cervical smear test (PAP) is a simple procedure which involves gently scraping some cells from the surface of the cervix and putting them on a slide. The cells are then examined under a microscope in the laboratory to see if they are normal.

Colposcopy is used to look at the cervix. It combines a bright light with a magnifying lens to make tissue easier to see. A colposcopy is usually done in the doctor’s office or clinic to check for abnormal cell growth. A biopsy is conducted under local anesthesia and pathologists, then the tissue is checked under a microscope for abnormal cells.

Cytology has low sensitivity for detecting CIN2 or worse. inaccuracy due to high variability between cytopathologists and between laboratories. It identifies women with cancer precursors but not women at the risk of developing them.

Though there are several methods of preventing cervical cancer, prevention by vaccination is emerging as the most effective option. Two vaccines licensed globally are available in India; a quadrivalent vaccine, Gardasil™ marketed by Merck and a bivalent vaccine, Cervarix™ marketed by Glaxo Smith Kline. Both vaccines are manufactured by recombinant DNA technology that produces non-infectious virus-like particles comprised of the HPV protein. Clinical trials with both vaccines have shown efficacy against CIN and adenocarcinoma caused by HPV strains. These vaccines do not protect against the serotype with which infection has already occurred before vaccination.

Cervical cancer is preventable and curable. There is a need to create awareness about the disease and its causal agents. It is possible to work to realize a society that is free of cervical cancer.

(Maj Neerja Masih (Veteran) MSc, PhD, MBA (I&R) is Head of Department of Biotechnology, Isabella Thoburn College, Lucknow)