Cervical Cancer - Signs Symptoms Treatment

Cervical Cancer

Prevalence

Cervical cancer is the second most common cancer in women after Breast Cancer

It has been estimated that 500,000 cases are diagnosed annually in the world and 80% of these are in the developing countries.

Cause of Cervical Cancer

• The relationship between cervical cancer and sexual activity was first noted more that 150 years ago.
• Since then it has been assumed that sexually transmitted infection may be the underlying mechanism.
• Many sexually transmitted infections have been suggested and linked to the disease. Perhaps the greatest difficulty has been that those who have acquired one sexually transmitted disease have been at risk of acquiring others.
• A variety of possible organisms have been implicated including Chlamydia trachomatis and herpes simplex.
• Only in the last twenty years have studies of cervical cancer demonstrated that at least 99.8% are associated with the human papillomavirus (HPV). There are many ‘types’ of HPV with HPV type 16 accounting for 50%, HPV 18 for 12%, HPV 45 for 8% and HPV 31 for 5%.
• Human papillomavirus (HPV) infection is a necessary factor in the development of nearly all cases of cervical cancer.^{9601, 9901} The virus cancer link works by triggering alterations in the cells of the cervix, leading to the development of cervical intraepithelial neoplasia which may in turn lead to cancer. Women who have many sexual partners (or who have sex with men or women who had many partners) have a greater risk.

An effective HPV vaccine against the two most common cancer-causing strains of HPV has recently been licensed in the U.S. . These two HPV strains together are responsible for approximately 70%⁰⁶⁰¹ of all cervical cancers. Experts recommend that women combine the benefits of both programs by seeking regular Pap smear screening, even after vaccination.

Acquisition of HPV does not necessarily mean that pre-malignancy or malignancy of the cervix will occur. Experts believe that 20% of women will acquire HPV at some time in their lives but the virus is removed from the body in the majority. A number of factors determine whether the HPV will not be eliminated and whether pre-malignancy and then malignancy will occur. Some people have a genetic predisposition to malignancy. Smoking reduces the efficiency of the immune system increasing the risks. The socially disadvantaged are most at risk of cervical cancer. The condom method of contraception provides protection against cervical cancer. Women who have used oral contraception are twice as likely to have high grade pre-malignant conditions of the cervix compared to those who never used it probably because they have been less likely to have used a barrier method of contraception.

More than 250 types of HPV are acknowledged to exist (some sources indicate more than 200 subtypes). Of these, 15 are classified as high-risk types (16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68, 73, and 82), 3 as probable high-risk (26, 53, and 66), and 12 as low-risk (6, 11, 40, 42, 43, 44, 54, 61, 70, 72, 81, and CP6108),⁰³⁰¹ but even those may cause cancer. Types 16 and 18 are generally acknowledged to cause about 70% of cervical cancer cases. Together with type 31, they are the prime risk factors for cervical cancer.⁹⁹⁰²

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 not all women infected with HPV develop cervical cancer.⁰⁶⁰² 

Despite the development of an HPV vaccine, some researchers argue that routine neonatal male circumcision is an acceptable way to lower the risk of cervical cancer in their future female sexual partners. Others maintain that the benefits do not outweigh the risks and/or consider the removal of healthy genital tissue from infants to be unethical as it cannot be reasonably assumed that a male would choose to be circumcised. There has not been any definitive evidence to support the claim that male circumcision prevents cervical cancer, although some researchers say there is compelling epidemiological evidence that men who have been circumcised are less likely to be infected with HPV. However, in men with low-risk sexual behaviour and monogamous female partners, circumcision makes no difference to the risk of cervical cancer.

 

Related Medical Abstracts - Click on the paper title:-

• Prophylactic human papillomavirus vaccines.(2006-01)
• HPV-mediated cervical carcinogenesis: concepts and clinical implications.(2006-02)
• Epidemiologic classification of human papillomavirus types associated with cervical cancer.(2003-01)
• Human papillomavirus is a necessary cause of invasive cervical cancer worldwide.(1999-01)
• Human papillomavirus is a necessary cause of invasive cervical cancer worldwide.(1999-02)
• Case-control study of oestrogen replacement therapy and risk of cervical cancer (1997-01).
• Human papillomavirus DNA in uterine cervix squamous cell carcinoma and adenocarcinoma detected by polymerase chain reaction.(1996-01)

Signs and symptoms of Cervical Cancer

The early stages of cervical cancer may be completely asymptomatic.Vaginal intermenstrual bleeding, contact post coital bleeding or, on ocasion, 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, there may be signs or symptoms associated with metastases (secondaries).

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 feces from the vagina, and bone fractures.

Picture of a cervical cancer

Cervical cancer photograph

Picture of cervical cancer - hysterectomy specimen.

Diagnosis of Cervical Cancer - Biopsy procedures

Whereas the pap smear is an effective screening test for pre-malignancy, confirmation of the diagnosis of cervical cancer or pre-cancer requires a biopsy of the cervix. This is often done at colposcopy, a magnified visual inspection of the cervix aided by using an acetic acid 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.

 

Pathological  types of Cervical Cancer

Cervical intraepithelial neoplasia (CIN), the precursor to cervical cancer, is often diagnosed on examination of cervical biopsies by a pathologist. Histologic subtypes of invasive cervical carcinoma include the following:

• squamous cell carcinoma (about 80-85%)
• adenocarcinoma

Staging

The stage of a cancer describes its size and whether it has spread beyond its original site. Knowing the extent of the cancer and the grade helps the doctors to decide on the most appropriate treatment.

The stages of cervical cancer are described below:

Stage 1 The cancer cells are only within the cervix.

Stage 2 The tumour has spread into surrounding structures such as the upper part of the vagina or tissues next to the cervix.

Stage 3 The tumour has spread to surrounding structures such as the lower part of the vagina, nearby lymph nodes, or tissues at the sides of the pelvic area. Sometimes a tumour that has spread to the pelvis may press on one of the ureters (the tubes through which urine passes from the kidneys to the bladder). If the tumour is causing pressure on a ureter there may be a build up of urine in the kidney.

Stage 2 or 3 tumours are called locally advanced cervical cancer.

Stage 4 The tumour has spread to the bladder or bowel or beyond the pelvic area. This stage includes tumours that have spread into the lungs, liver or bone, although this is not common.

If the cancer comes back after initial treatment this is known as recurrent cancer.

Grading

The grade of a cancer gives an idea of how quickly it may develop. To find the grade of your cancer, your doctors will look at a sample of the cancer (a biopsy) under the microscope. It may be graded as:

• Grade 1 (low grade) – the cancer cells tend to be slow growing, look quite similar to normal cells (are 'well differentiated') and are less likely to spread than higher grades.

• Grade 2 (moderate grade) – the cells look more abnormal and are slightly faster-growing.

• Grade 3 (high grade) – the cancer cells tend to be more quickly growing, look very abnormal (are 'poorly differentiated') and are more likely to spread than low-grade cancers.

Treatment of Cervical Cancer

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.⁰⁶⁰³ 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. Due to the possible risk of cancer spread to the lymph nodes in stage 1b cancers and some stage 1a cancers, the surgeon may also need to remove some lymph nodes from around the uterus for pathologic evaluation.

It is recommended for patients to practice vigilant prevention and follow up care including pap screenings/colposcopy, with biopsies of the remaining lower uterine segment as needed (every 3-4 months for at least 5 years) to monitor for any recurrence in addition to minimizing any new exposures to HPV through safe sex practices until one is actively trying to conceive.

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 tumors (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.

• Radical trachelectomy with laparoscopic lymphadenectomy: review of oncologic and obstetrical outcomes.(2006-03)

Prognosis of Cervicaql Cancer

Prognosis depends on the stage of the cancer. With treatment, 80 to 90% of women with stage I cancer and 50 to 65% of those with stage II cancer are alive 5 years after diagnosis. Only 25 to 35% of women with stage III cancer and 15% or fewer of those with stage IV cancer are alive after 5 years. As the cancer metastasizes to other parts of the body, prognosis drops dramatically because treatment of local lesions is generally more effective than whole body treatments such as chemotherapy.

Cervical Screening - Interval

Current evidence would suggest that, if an initial screen is negative, the next screen should be three years later. If repeat smears are negative a five year screening programme would seem reasonable. The World Health Organization has recommended that in countries where resources are limited, every woman should have screening at least once in her life. The Institute of Cytology and Preventative Oncology in India suggest that the optimum time for once in a life-time screening would be at age 45 years.

Related Medical Abstracts - Click on the paper title:-

• Cervical cancer in Australia and the United Kingdom: comparison of screening policy and uptake, and cancer incidence and mortality. (2006-01)
• No major difference between population screening for cervical carcinoma at the present screening interval of 5 years and the former interval of 3 years (2004-01)
• Population-based cervical screening with a 5-year interval in The Netherlands. Stabilization of the incidence of squamous cell carcinoma and its precursor lesions in the screened population. (2004-02)
• Risk of cervical cancer associated with extending the interval between cervical-cancer screenings. (2003-01)
• Health authority cervical screening recall policies and time since last smear: a retrospective cohort analysis in the north west England. (2003-02)
• Cervical screening interval: costing the options in one health authority. (1999-01)
• Relation between the incidence of invasive cervical cancer and the screening interval: is a five year interval too long? (1996-01)

Cervical Screening and Prevention of Cervical Cancer

Epidemiologists in Sweden have recently reviewed the literature on screening results. They found seventeen cancer registries large enough and existing long enough to evaluate the effects of screening. Incidence rates of cervical cancer fell by more than 25% in eleven of the registries ranging from 27% in Norway to 77% in Finland. Following the initial fall in incidence with the introduction of screening, the incidence of cervical cancer has remained stable over the last 20 years in developed countries.

Figure 21.6 shows the falling rates in the incidence of cervical cancer and deaths from the disease in the UK from 1955 1985. This fall has been associated with an increase in diagnosis and treatment of pre-malignancy. The GB age-standardised (European) incidence rate for cervical cancer has decreased by 45% since 1975.

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This is the personal website of David A Viniker MD FRCOG, Consultant Obstetrician and Gynaecologist at Whipps Cross University Hospital, London - Specialist Interests - Reproductive Medicine including Infertility, PCOS, PMS, Menopause and HRT.

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