Cervical Cancer is common in India, with around 1.2 Lakh cases each year, making it the second most common cancer among Indian women. It is also one of the top causes of death among Indian women diagnosed with cancer. Lack of widespread cervical cancer screening and delays in timely treatment seem to be the major contributors to this low survival rate in Indian women with cervical cancer.
Who is at risk?
Factors that can contribute to the development of cervical cancer include poor hygiene, lack of screening for cervical cancer, HPV (Human Papilloma Virus) infection, early age at first intercourse, multiple sexual partners, tobacco consumption, alcohol, and the use of oral contraceptive pills.
How does HPV cause cervical cancer?
Persistent infection with certain HPV types is necessary for the development of nearly 95% of cervical cancers. It does this by incorporating its DNA into an infected cell’s genetic makeup, eventually causing the inactivation of certain protective genes in humans that prevent the development of cancer. HPV types 6 and 11 cause anogenital warts, while types 16, 18, 31, and 33 are associated with the development of cancer.
Most HPV infections are transient. However, when the virus persists in the body, it can lead to the development of precancerous changes in the cervix over one or two decades. Most of these changes may resolve on their own, but in women with more advanced precancerous changes, a third will go on to eventually develop cervical cancer.
HPV Vaccination
As one of the few vaccine-preventable cancers, perhaps the easiest way to prevent cervical cancer is through preventing the HPV infection itself, known as primary prevention. This is accomplished through the use of HPV vaccines, preferably two doses between 9 and 14 years of age, with catch-up vaccination advisable till the age of 26 years. The currently available vaccines can protect against two, four, or up to nine HPV types, depending on the vaccine chosen.
Screening for Cervical Cancer
Secondary prevention, which is not allowing pre-cancerous lesions to develop into cancer, is done using screening. Screening can be done using Pap smears, HPV testing, and visual inspection. For Pap smears, cells are collected from the cervix to look for precancerous changes. Various commercially available tests can also be used to detect HPV DNA/ RNA in cervical cell samples, and this is recommended by current WHO guidelines as the best first choice for screening. When Pap smear and HPV testing are done together, it’s called co-testing.
In low-resource settings, visual inspection methods are more commonly employed, where either acetic acid (VIA) or an iodine preparation (VILI) are applied to the cervix. A positive test is indicated by the presence of white areas, although all positive tests are not indicative of a precancerous or cancerous lesion.
Recommended Screening
• In resource-rich settings, cervical cancer screening is recommended to start at 21 years, with PAP smears once every 3 years till the age of 30. Alternatively, screening can be started at the age of 25 years, with HPV testing once in 5 years.
• Between the ages of 30 and 65 years, primary HPV testing or co-testing can be done once every 5 years, or, if HPV testing is not feasible, PAP smears once every 3 years.
In India, screening is recommended at least once in 5 years for people between the ages of 30 and 65, ideally with HPV testing. However, screening rates are low, with less than 2% of eligible women undergoing screening for cervical cancer, compared to 40-70% in developed countries. For individuals interested in cervical cancer screening, we strongly recommend HPV testing over PAP smears.
The 90-70-90 Initiative
As part of a Global Strategy to eliminate cervical cancer, the World Health Organization (WHO) has set targets for cervical cancer vaccination, screening, and treatment: 90% of girls should have received the HPV vaccine by the age of 15, 90% of women with pre-cancerous lesion or invasive cancer should receive appropriate treatment, and 70% of women should be screened at least once by the age of 35 years and again by the age of 45 years using DNA-based HPV tests.
Treatment
Precancerous cervical lesions can be treated using laser therapy, cryotherapy, or other minor surgical procedures. Early cervical cancers may be treated by surgery alone or with surgery followed by radiotherapy. In locally advanced cervical cancers, definitive radiotherapy along with chemotherapy is the treatment of choice. Radiotherapy will include both External Beam radiotherapy and Brachytherapy. Open surgeries are generally preferred over keyhole surgeries. Last year, the immunotherapy drug Pembrolizumab was approved for use in certain patients with cervical cancer undergoing chemoradiation, as it was found to improve survival. Immunotherapy works by activating and increasing the body’s ability to fight and destroy cancer cells, unlike chemotherapy, which directly kills cancer cells.
Immunotherapy with Pembrolizumab is also useful in women with cervical cancer that has spread to other parts of the body if the tumor cells express a protein called PDL1. For those without this protein, a targeted therapy called Bevacizumab can be added to the chemotherapy, which works partly by reducing the growth of new blood vessels to the tumor, causing the tumor cells to die of starvation. Tisotumab is another targeted therapy that was approved for stage 4 cervical cancers last year, It combines a chemotherapy drug with a targeting agent so that the chemotherapy mainly attacks the cancer cells. One more option here is Trastuzumab Deruxtecan, again approved only last year for use in stage 4 cervical cancer if the cancer cells over-express a protein called Her2. Even more treatment options are currently being evaluated in various trials around the world.
The Endgame
The WHO is working to eliminate cervical cancer as a public health problem through its Global Strategy for Cervical Cancer Elimination. If countries can meet the 90-70-90 targets by 2030, we will hopefully be able to eliminate cervical cancer by the turn of the century. However, as things stand, most developing countries, including India, are a long way from achieving those targets. Increased awareness regarding cervical cancer vaccination and screening and increased participation in these measures are needed.
Dr. Azgar Abdul Rasheed is an Associate Consultant in Medical Oncology at KIMSHEALTH Trivandrum