Dr. Suman Raj Tamrakar

Globally, cervical cancer is the second commonest cancer in female after breast cancer. In 2018, some 570,000 cases of cervical cancer were estimated to have occurred, with over 300,000 deaths. Around 80 per cent of cervical cancer cases occur in developing countries, and Nepal is one of them. This form of cancer is the commonest in girls and women aged between 15–44 years. In 2018, a total of 2,942 new cervical cancer cases were detected in the country. The disease killed as many as 1,928 patients in the same year.

Cervical cancer arises from the cervix (Wikipedia). It is an abnormal growth of cells that have the ability to invade or spread to other parts of the body. Cervical cancer typically develops from precancerous changes over 10-20 years. About 90 per cent of cervical cancer cases are squamous cell carcinomas while 10 per cent are adenocarcinoma, and a small number are other types. Initially, it can be symptomless. Later, it can be presented with abnormal vaginal bleeding, pelvic pain and foul smelling vaginal discharge. Pain and bleeding during and after sexual intercourse are unique features of cervical cancer.

Symptoms
When the disease is in an advanced stage, metastases may be present in the abdomen, lungs, or elsewhere. Symptoms of advanced cervical cancer could be loss of appetite, weight loss, fatigue, pelvic pain, back pain, leg pain, swollen legs, heavy vaginal bleeding, bone fractures, and leakage of urine or feces from the vagina. Human papillomavirus (HPV) infection causes more than 90 per cent of cases. However, most people with HPV infections do not develop cervical cancer. Human papillomavirus types 16 and 18 are the causes of about 75 per cent of cervical cancer cases worldwide, while 31 and 45 are the causes of another 10 per cent. Smoking, poor immune system, birth control pills, sexual intercourse at young age, and having multiple sexual partners are other risk factors. Genetic factors also contribute to cervical cancer risk.

The prevalence of HPV infection in Nepal is much higher. According to the Information Centre on HPV and Cancer (ICO), Nepal reports a prevalence of HPV 16 and or HPV 18 among women with low-grade squamous intraepithelial lesion (LSIL) and high-grade squamous intraepithelial lesion (HSIL), and cervical cancer are 30.2, 63.4, and 80.3 per cent, respectively.

Its diagnosis is typically done through cervical screening followed by a biopsy. The Pap smear test (Papanicolaou test) can be used as a screening test for cervical cancer. Other screening tests are visual inspection with acetic acid (VIA), Lugol's iodine (VILI) and HPV DNA testing. Confirmation of the diagnosis of cervical cancer or precancer requires a biopsy of the cervix. This is often done through colposcopy, a magnified visual inspection of the cervix to highlight abnormal cells on the surface of the cervix.

Women aged between 21 and 65 should get their pap tested every three years. However, there are a number of recommended options for screening cervical cancer among age group of 30-65 years. This includes cervical cytology every three years, HPV testing every five years, or HPV testing together with cytology every five years.

Cervical intraepithelial neoplasia (CIN), the potential precursor (premalignant dysplastic changes) to cervical cancer, is often diagnosed on examination of cervical biopsies by a pathologist. The term ‘CIN’ was developed to place emphasis on the spectrum of abnormality in these lesions, and to help standardise treatment. It classifies mild dysplasia as CIN1, moderate dysplasia as CIN2, and severe dysplasia and carcinoma in situ (CIS) as CIN3. Imaging modalities such as ultrasound, CT scan, and MRI have been used to look for alternating disease, spread of the tumor, and effect on adjacent structures. Typically, they appear as heterogeneous mass on the cervix.

Earlier, cervical cancer is staged by the FIGO system, which is based on clinical examination rather than surgical findings. However, the existing system allows use of different imaging or pathological methods for staging of the disease. Stage I means cervical cancer confined to cervix only, stage II denotes cervical cancer spreads to parametrium, stage III means cervical cancer spreads to lateral pelvic wall and stage IV indicates distant metastasis. The common site of distant metastasis includes lung, liver, bones, and supraclavicular nodes.

The treatment of cervical cancer varies worldwide because of the availability of skilled surgeons in radical pelvic surgery and need of fertility-sparing surgery. Microinvasive cancer (stage IA) may be treated by hysterectomy (removal of the whole uterus including part of the vagina). For stage IA2, the lymph nodes are removed as well. Alternatives include local surgical procedures such as a loop electrical excision procedure (LEEP) or cone biopsy. One more possible treatment option for women who want to preserve their fertility is a trachelectomy (removal of the cervix, upper vagina and parametrium i.e. tissue surrounding the cervix).

Early stages (IB1 and IIA less than 4 cm) can be treated with radical hysterectomy with removal of the lymph nodes or radiation therapy. Larger early-stage tumours (IB2 and IIA more than 4 cm) may be treated with chemo-radiation therapy. Advanced-stage tumors (IIB-IVA) are treated with chemoradiation therapy. Then after, palliative care will be the last option.
Prognosis depends on the stage of the cancer. The chance of a survival rate is nearly 100 per cent for women with microscopic forms of cervical cancer. With treatment, the five-year relative survival rate for the earliest stage of invasive cervical cancer stands at 92 per cent, and the overall (all stages combined) five-year survival rate is about 72 per cent. With treatment, 80-90 per cent of women with stage I cancer and 60-75 per cent of those with stage II cancer are survive five years after diagnosis. Survival rates decrease to 30-40 per cent for women with stage III cancer and 15 per cent or fewer for those with stage IV cancer five years after diagnosis.

Vaccines’ effectiveness
Regular cervical screening, HPV vaccines, sexual intercourse with condoms, sexual abstinence are the preventive measures for cervical cancer. Of them, HPV vaccines have shown very promising results. HPV vaccines (Gardasil, Gardasil 9, and Cervarix) help reduce the risk of cancerous or precancerous changes of the cervix and perineum by about 93 per cent and 62 per cent, respectively. The vaccines are between 92 per cent and 100 per cent effective against HPV 16 and 18 up to at least eight years. The HPV vaccines are typically given to females aged between 9 and 26. The vaccines may become the most effective if given before infection occurs. Though Hippocrates noted that cervical cancer was incurable in 400 BC, it can now be cured and/or prevented with consistent advancement in medical field.

(A professor, Tamrakar is the head of the Department of Obstetrics and Gynaecology at Kathmandu University (Dhulikhel Hospital). drsuman3947@gmail.com)