Cervical cancer: A preventable and treatable disease

Though cervical cancer is completely preventable, with screening exams and treatment, it continues to claim a considerable chunk of women population throughout the world. Considered the fifth most deadly cancer in women worldwide, cervical cancer affects about 16 per 100,000 women per year and kills about 9 per 100,000 per year, that is 800 women a day.

It remains unfortunate that about 83 per cent of the cases occur in developing countries, representing 15 per cent of female cancers. In Tanzania, cervical cancer ranks as the first most frequent cancer among women between 15 and 44 years of age. Tanzania is said to have a population of 10.97 million women aged 15 years and older who are at risk of developing cervical cancer. Current estimates indicate that every year 7,515 women are diagnosed with cervical cancer and 6,009 die from the disease though data is not yet available on the HPV burden in the general population of the country. However, in Eastern Africa, the region Tanzania belongs to, about 33.6 per cent of women in the general
population are estimated to harbour cervical HPV infection at a given time.

Pap smear screening can identify potentially precancerous changes. Treatment of high grade changes can prevent the development of cancer. In developed countries, the widespread use of cervical screening programmes has reduced the incidence of invasive cervical cancer by 50 per cent or more.

Human papillomavirus (HPV) infection is a necessary factor in the development of nearly all cases of cervical cancer. HPV vaccine effective against the two strains of HPV that cause the most cervical cancer has been licensed in the US and the EU. These two HPV strains together are currently responsible for approximately 70 per cent of all cervical cancers. Since the vaccine only covers some high-risk types, women should seek regular Pap smear screening, even after vaccination.

Signs and symptoms
The early stages of cervical cancer may be completely asymptomatic. Vaginal bleeding, contact bleeding or (rarely) a vaginal mass may indicate the presence of malignancy. Also, moderate pain during sexual intercourse and vaginal discharge are symptoms of cervical cancer. In advanced disease, metastases may be present in the abdomen, lungs or elsewhere.

Symptoms of advanced cervical cancer may include: Loss of appetite, weight loss, fatigue, pelvic pain, back pain, leg pain, single swollen leg, heavy bleeding from the vagina, leaking of urine or faeces from the vagina, and bone fractures.

Causes
Human papillomavirus infection. The most important risk factor in the development of cervical cancer is infection with a high-risk strain of human papillomavirus. The virus cancer link works by triggering alterations in the cells of the cervix, which can lead to the development of cervical intraepithelial neoplasia, which can lead to cancer. Women who have many sexual partners (or who have sex with men who had many other partners) have a greater risk.

The medically accepted paradigm, officially endorsed by the American Cancer Society and other organizations, is that a patient must have been infected with HPV to develop cervical cancer, and is hence viewed as a sexually transmitted disease, but most women infected with high risk HPV will not develop cervical cancer. Use of condoms reduces, but does not always prevent transmission. Likewise, HPV can be transmitted by skin-to-skin-contact with infected areas. In males, HPV is thought to grow preferentially in the epithelium of the glans penis, and cleaning of this area may be preventative.

The American Cancer Society provides the following list of risk factors for cervical cancer: human papillomavirus (HPV) infection, smoking, HIV infection, chlamydia infection, dietary factors, hormonal contraception, multiple pregnancies, exposure to the hormonal drug diethylstilbestrol (DES) and a family history of cervical cancer. There is a possible genetic risk associated with HLA-B7.

Diagnosis

While the pap smear is an effective screening test, confirmation of the diagnosis of cervical cancer or pre-cancer requires a biopsy of the cervix. This is often done through colposcopy, a magnified visual inspection of the cervix aided by using a dilute acetic acid (e.g. vinegar) solution to highlight abnormal cells on the surface of the cervix. Further diagnostic procedures are loop electrical excision procedure (LEEP) and conization, in which the inner lining of the cervix is removed to be examined pathologically. These are carried out if the biopsy confirms severe cervical intraepithelial neoplasia.

Treatment
Microinvasive cancer (stage IA) is usually treated by hysterectomy (removal of the whole uterus including part of the vagina). For stage IA2, the lymph nodes are removed as well. An alternative for patients who desire to remain fertile is a local surgical procedure such as a loop electrical excision procedure (LEEP) or cone biopsy.

If a cone biopsy does not produce clear margins, one more possible treatment option for patients who want to preserve their fertility is a trachelectomy. This attempts to surgically remove the cancer while preserving the ovaries and uterus, providing for a more conservative operation than a hysterectomy. It is a viable option for those in stage I cervical cancer which has not spread; however, it is not yet considered a standard of care, as few doctors are skilled in this procedure.

Even the most experienced surgeon cannot promise that a trachelectomy can be performed until after surgical microscopic examination, as the extent of the spread of cancer is unknown. If the surgeon is not able to microscopically confirm clear margins of cervical tissue once the patient is under general anesthesia in the operating room, a hysterectomy may still be needed. This can only be done during the same operation if the patient has given prior consent.

Early stages (IB1 and IIA less than 4 cm) can be treated with radical hysterectomy with removal of the lymph nodes or radiation therapy. Radiation therapy is given as external beam radiotherapy to the pelvis and brachytherapy (internal radiation). Patients treated with surgery who have high risk features found on pathologic examination are given radiation therapy with or without chemotherapy in order to reduce the risk of relapse. 

Larger early stage tumours (IB2 and IIA more than 4 cm) may be treated with radiation therapy and cisplatin-based chemotherapy, hysterectomy (which then usually requires adjuvant radiation therapy), or cisplatin chemotherapy followed by hysterectomy.

Advanced stage tumors (IIB-IVA) are treated with radiation therapy and cisplatin-based chemotherapy.

Prevention
The widespread introduction of the Papanicolaou test, or Pap smear for cervical cancer screening has been credited with dramatically reducing the incidence and mortality of cervical cancer in developed countries. Abnormal Pap smear results may suggest the presence of cervical intraepithelial neoplasia (potentially premalignant changes in the cervix) before a cancer has developed, allowing examination and possible preventive treatment. Recommendations for how often a Pap smear should be done vary from once a year to once every five years. The ACS recommends that cervical cancer screening should begin approximately three years after the onset of vaginal intercourse and/or not later than twenty-one years of age.

The HPV test is a newer technique for cervical cancer triage which detects the presence of human papillomavirus infection in the cervix. It is more sensitive than the pap smear (less likely to produce false negative results), but less specific (more likely to produce false positive results) and its role in routine screening is still evolving.

HPV vaccines have come in handy in fighting the disease as they are targeted at girls and women aged between 9 to 26 because the vaccine only works if given before infection occurs; therefore, public health workers are targeting girls before they begin having sex. The use of the vaccine in men to prevent genital warts and interrupt transmission to women or other men is initially considered only a secondary market.