The NCI Dictionary of Cancer Terms defines the cervix as the ‘lower, narrow end of the uterus that forms a canal between the uterus and vagina.’ This seemingly innocuous definition fails to capture the sheer statistics of the invasive nature of cancer affecting the cervix which has led to an estimated 570 000 new cases and 311 000 deaths in 2018. (1) The human cervix is anatomically divided into an endocervix continuing upwards until the uterine cavity, lined by simple columnar epithelium, and an ectocervix which leads downwards to the vagina and is covered by stratified, squamous non-keratinised cells. According to American Cancer Society, most of the cancers (9 out of 10) affect the ectocervix, i.e. squamous cell carcinoma while adenocarcinomas primarily target the endocervix and are specially associated with HPV 18 infections with greater incidence among younger women. It has a bimodal peak of incidence, occurring with equal vigour among women in the age groups of 30-40 and 50-60 years, with the women falling in the age group of 55-65 years being at the highest risk. Worldwide cervical cancer is the 4th most common cancer in terms of mortality and incidence with India accounting for nearly one-third of the global cervical cancer deaths with an estimated death of more than 200 Indian women on a daily basis. (2) With such dire numbers confronting us, it is of utmost importance that cervical health is stressed upon, especially since 91% of all the cases are caused due to infection by human papillomavirus (HPV) and early detection and treatment vastly improves the chances of survival to more than 85%. (3)
The most common presentation of cervical cancer involves irregular vaginal bleeding, post-coital bleeding coupled with unusual vaginal discharge. Apparently harmless symptoms of unusual bleeding, swelling of legs, bone pain and/or changes in bowel habits especially in post-menopausal women should not be ignored and prompt medical consultation is advised. The greatest risk factor for developing cervical cancer is getting infected by HPV, an icosahedral non-enveloped virus containing double-stranded DNA. Around 660 million people globally get infected with HPV each year. Even though over 100 varieties of HPV exist, more than 40 are transmitted by sexual contact while vertical transmission from mother to child either during pregnancy or during labour is a rare, yet probable, occurrence. HPV most commonly causes warts which are small, benign growths on the skin caused due to hypertrophy of all the layers of the dermis followed by hyperkeratosis of the horny layer. HPV is further sub-classified into the low-risk types, namely types 6 and 11, causing warts which spontaneously regress without any further complications. The high-risk types like types 16 and 18 are strongly linked to the incidence of cervical, vaginal and vulval cancer following infection in more than 99.7% of all the cases. Strong correlation exists between cervical cancer and HPV as DNA of HPV have been detected in pre-malignant lesions of the male and female genital tract and HPV types 16, 18 and 31 have been detected in 60 to 100% cases of cervical cancer. It takes around 20 years to develop invasive carcinoma following HPV infection so with proper screening, detection, and management we can succeed in saving millions of women from the clutches of an untimely demise. Other risk factors include multiple sexual partners, unprotected sexual practises, early marriage, and childbirth especially for women under the age of 18 years. A weakened immune system also increases a woman’s susceptibility towards developing cervical cancer as cases have been recorded where HIV positive patients, women taking immunosuppressants have progressed faster into invasive cancer following a precancerous growth. Smoking is another risk factor as tobacco damages the immune system and the other harmful carcinogens present in cigarette smoke contribute towards the development of cervical cancer. The economic status plays a pivotal role as cervical cancer is the first and second highest cause of cancer deaths in low and lower-middle-income countries respectively. (4) Women in low and medium-HDI (Human Development Index) countries have limited access to basic health care services and a nutritionally rich diet containing adequate quantities of fruits and vegetables which invariably increases their risk for developing cervical cancer. Lastly, a family history of cervical cancer and long-term use of OCPs (Oral Contraceptive Pills) have been listed as risk factors too.
In accordance with the WHO’s comprehensive approach to cervical cancer prevention and control, there should be a development of a multi-pronged approach at the primary, secondary, and tertiary levels. Currently there are 2 HPV vaccines commercially available – Cervarix, which develops immunity against HPV types 16 and 18, and Gardasil which protects against types 6, 11, 16 and 18. For both boys and girls in the age group of 9-14 years, 2 doses are recommended at 0 months and 6 months, respectively. For women in the age-group of 15-45 years, 3 doses are required at 0, 2, and 6 months. Rigorous implementation of vaccination coupled with proper health information and warnings targeting the adolescent population regarding tobacco use and unprotected sexual practises can play major roles in combating this lethal yet treatable form of cancer. Common barriers to early detection involve lack of awareness and knowledge, fears regarding screening, cancer stigma and sociocultural barriers. These must be overcome by the education and training of community health workers and caregivers, health promotion, and organisation of cancer screening camps in collaboration with the government. Secondary prevention entails screening, especially in women above 30 years of age, followed by immediate treatment as quickly as possible for precancerous lesions. Routine gynaecological examinations like Pap smears, biopsy, endocervical curettage, USG along with immediate histopathological studies of any suspicious findings are recommended. Tertiary care level involves complex diagnosis involving MRI and CT scans to determine the extent of spread of cancer, specialised treatment appropriate for the respective stage of cervical cancer, along with supportive and palliative care. Improvement of healthcare services with the introduction of a well-defined clinical referral pathway of diagnosis and staging, quicker delivery of pathology reports along with prompt set-up of a treatment plan, public awareness programmes harping on the importance of safe sexual practises, usage of condoms and greater prioritisation of the nutritional requirements of women are some of the initiatives which can be taken up by different governments to effectively curb the incidence of cervical cancer. To end cervical cancer however, 7 out of 10 women should be screened by 35 years of age. Screening remains the first line of defence with ACS (American Cancer Society) recommending that women in the age group of 21-29 years have a Pap test performed every 3 years while those above 30 years of age should get a Pap test done along with an HPV test until 65 years of age after which a normal Pap test every 3 years is sufficient.
The WHO aims to accelerate action to achieve Goal 3.4 of the Sustainable Development Goals (SDGs) in order to reduce premature mortality from non-communicable diseases, including cancer, by one-third by 2030 and thus has established the 90-70-90 goals for 2030. If by the year of 2030, 90% of girls are vaccinated by 15 years, 70% of women are screened and 90% are treated, then we can end up saving over 62 million lives by 2120. So as the future healthcare providers of tomorrow, let’s join hands and pledge for eradicating HPV and changing the lives of countless women all around the world.
REFERENCES:
(1) Ferlay J, Ervik M, Lam F, Colombet M, Mery L, Piñeros M.
Global Cancer Observatory: Cancer Today. Lyon, France ( https://gco.iarc.fr/today/home)
(2) World health Organization (WHO). International Agency for Research on Cancer. India factsheet. Lyon: IARC; 2018.(https://gco.iarc.fr/today/data/factsheets/populations/356-india-fact-sheets.pdf)
(3) https://www.nccc-online.org/hpvcervical-cancer/cervical-cancer-overview/
(4) World Health Organization. (2020). WHO framework for strengthening and scaling-up of services for the management of invasive cervical cancer. World Health Organization. (https://apps.who.int/iris/handle/10665/337539)