Cervical Cancer Causes, Symptoms, Diagnosis, Staging and Treatment

Cancer and its Treatment

Cervical cancer is the 6^th most frequent cancer amazing dong females in the UK. Not only have the risk factors for this disease been determined but a reliable screening test in the form of a Pap smear has also been established. Moreover, the slow and predictable behavior pattern of this disease is now thoroughly understood. (Gaiotti,D., Chung, J., Iglesias, M., Nees, M., Baker, P.D., Evans, C.H., and Woodworth, C.D., 2000)

” A Pap smear can save your lives because of its efficacy,” said Susan Spires, M.D., assistant professor, Department of Pathology and Laboratory Medicine, UK College of Medicine. “All females should receive annual Pap tests for themselves and those who enjoy them.”

Though, the liquid based cytology (LBC) is currently in the process of introducing the LBS as a standard tool for screening. LBC is anticipated to lower the inadequate rate as retaining or improving the sensitivity and specificity of the smear test. Use of LBC would permit current laboratory workload to be coped with the on hand workforce and the remaining cell suspension can be used for reaction of human papillomavirus testing or other ancillary tests such as chlamydia or gonococcus recognition or molecular organic tests for markers of neoplastic succession. The difficulties of LBC comprise: main changes in the routine compilation, transport and storage of cervical scrape samples and equally cytotechnologists and cytopathologists need further training to evaluate LBC slides.

Recently, there has been a study which suggested that a relationship exists between contraceptive pills and cancer of the cervix. It was claimed that women taking these pills had a higher incidence of this disease than did nonusers. However, knowledgeable experts have criticized this study on two important points. The so-called normal women used as a comparison to the group of women on pills may have differed in significant ways from the latter group. If the nonusers had less frequent sexual intercourse or fewer children, they would be expected to have a lower incidence of cervical cancer related to these factors alone. A woman with cervical cancer is often found to have begun intercourse early in her life, to have had several sexual partners, and to belong to a low socioeconomic class. Therefore, before comparisons of the effect of contraceptives on cervical cancer can be made, members of the pill-taking group and the non-pill-taking group must be similar in age of first intercourse, number of partners, and social class. Another criticism of this study was based on disagreement with the microscopic interpretation of the tissue changes. Many observers felt that the diagnosis of cancer was being made in tissues where there was no evidence of it. Precisely, there is no indication that hormonal contraception can cause cervical cancer. On the other hand, cancer of the lining of the uterus as opposed to that of the cervix may even be made less likely by the use of contraceptive pills (Hollander MC, Sheikh MS, Yu K, Zhan Q, Iglesias M, Woodworth C, and Fornace AJ Jr, 2001). During the past decade, many cases of uterine-lining cancer have been treated with high doses of progestins and in some cases the extent of the cancer has been lessened. It is felt by many physicians that progestins given as contraceptive pills may in the long run provide considerable protection against the development of this type of cancer.

Epidemiology & Aetiology

Cervical cancer death rate has been lower in Britain in past 10 years. The impact of populace based screening in the precedent two decades appears lower than that in Britain and, though mortality is progressively lessening. National Cancer Registry (National Cancer Registry, 2003) illustrates that the frequency of invasive cervical cancer reduced by 1.1% yearly between 1994 and 1999, but no occurrence of information is accessible for the period before 1994. It is probable, though dubious, that the trend might have been in the contradictory direction in the eighties and nineties. main changes in sexual behavior appear to have occurred throughout that time, as proofed by an amplify in the percentage of births outside marriage to thirty percent and in sexually spread infection, including a ten fold increase in the occurrence of anogenital warts between 1989 and 2000. Though, similar changes have occurred in the UK devoid of an analogous increase in cervical cancer mortality (Central Statistics Office, 2002).

The subsequent prospect is of a decline in survival, though this seems improbable in view of the general raise in cervical cancer survival all through Europe throughout this period.

Also Study: Alternative Therapies of Cancer

Early detection through effectual screening is a main issue in improving survival. If all women in the target group were having usual screening, this degree of activity would associate, over a three year period, to 60 percent coverage of the female population aged 25–60 years. Though, no information is obtainable on the ages of women screened, nor on their screening history, so women of the wrong age, or those with current negative tests, might make up a noteworthy quantity of the total.

In 2000, there were 2,424 new registrations of invasive cervical cancer in England (National Statistics, 2000)

Cervical cancer incidence fell by 42 per cent between 1988 and 1997 (England and Wales). This fall is directly related to the cervical screening programme. (National Statistics, 2000)

There was a 25 per cent decrease in the incidence rate of cervical cancer for women under the age of 70 from 1990 to 1992. This has been attributed to a rapid increase in coverage of the cervical screening programme which occurred from 1989 onwards (Swerdlow, Silva and Doll OUP 2001).

In 1995, there were 10.4 newly diagnosed cases of cervical cancer per 100,000 women (4National Statistics MB1 No 28 Cancer statistics Registrations 1995-1997). By 1999, this had fallen to 9.3 per 100,000 women (National Statistics MB1 No 30 Registrations of cancer diagnosed in 1999).

Cervical screening now saves approximately 4,500 lives per year in England (Julian Peto et al, 249-56). Cervical screening prevents up to 3,900 cases of cervical cancer per year in the UK (Sasieni, British Journal of Cancer 1996 Apr; 73(8):1001-5)

21,617 women in England were found to have the most severe type of CIN (CIN 3). UK incidence rates are slightly below the European Union average while the mortality rates are slightly above (Cancer Stats, Cervical Cancer – UK, January 2003), An estimated 471,000 new cases of cervical cancer are diagnosed each year in the world with 80 per cent of these occurring in the less developed world

• Women aged 15-99 with cervical cancer have a 1-year survival rate of 82.3% in England and Wales 1991-95. (Cancer Survival, National Statistics)
• Women aged 15-99 with cervical cancer have a 5-year survival rate of 62.2% in England and Wales 1991-95.  (Cancer Survival, National Statistics)
• Women aged 15-39 with cervical cancer have a 1-year survival rate of 94% in England and Wales 1991-95. (Cancer Survival, National Statistics)
• Women aged 15-39 with cervical cancer have a 5-year survival rate of 80% in England and Wales 1991-95 (Cancer Survival, National Statistics)
• Women aged 40-49 with cervical cancer have a 1-year survival rate of 90% in England and Wales 1991-95 (Cancer Survival, National Statistics)
• 5-year survival rate for women aged 40-49 with cervical cancer is 73% in England and Wales 1991-95 (Cancer Survival, National Statistics)
• Women aged 50-59 with cervical cancer have a 1-year survival rate of 84% in England and Wales 1991-95 (Cancer Survival, National Statistics)
• In England and Wales, the 5-year survival rate for females between 50 and 59 years of age with cervical cancer is 62 percent. (Cancer Survival, National Statistics)
• Women aged 60-69 with cervical cancer have a 1-year survival rate of 78% in England and Wales 1991-95  (Cancer Survival, National Statistics)
• The 5-year survival rate in England and Wales 1991-95 for females aged 60-69 with cervical cancer is 54%. (Cancer Survival, National Statistics)
• In England and Wales, the 1-year survival rate for females between 70 and 79 years of age with cervical cancer is 65 percent. (Cancer Survival, National Statistics)
• Women aged 70-79 with cervical cancer have a 5-year survival rate of 37% in England and Wales 1991-95 (Cancer Survival, National Statistics)
• Women aged 80-99 with cervical cancer have a 1-year survival rate of 49% in England and Wales 1991-95  (Cancer Survival, National Statistics)
• In England and Wales, the 5-year survival rate for females between 80 and 99 years of age with cervical cancer is 25 percent. (Cancer Survival, National Statistics)

Cervical Cancer Causes — HPV

Research concludes that the two primary risk factors for cervical cancer are a highly active sexual life and low socioeconomic status. If a woman engages in sexual activity before the age of 20 and has multiple sexual partners, her risk of cervical cancer rises considerably (Dionne, Carla., 2001). For example, the risk of prostitutes incurring cervical cancer is 4 times greater than that of celibate women. In addition, women of low socioeconomic status have 5 times the risk of developing cervical cancer as do those of higher status.

In fact, cervical cancer is now considered a sexually transmitted disease. Many authorities believe that a sexually transmitted virus, the human papillomavirus (HPV), is the probable agent of transmission because this virus is found in more than 90% of cervical cancers (Haas, Adelaide, and Susan Puretz., 2001). The object of intensive medical research, this virus is now known to infect 20% of sexually active women, only 1% of who eventually develop cervical cancer (Parker, William H., M.D., and Rachel L. Parker, 2003).

Human papillomavirus (HPV) is generally regarded as a sexually transmitted agent and some HPV types are etiologically related to cervical neoplasia. Sexual risk behavior has long been related to cervical neo-plasia.

Studies concerning cervical human papillomavirus infection (CHPI) as a sexually transmitted disease (STD) have been contradictory. Nonsexual modes of transmission of CHPI have been suggested. Genital warts are generally regarded to be sexually transmitted, although vertical transmission from mother to child does occur. Antibodies against HPV types 6, 16, and 18 as well as a high prevalence of HPV in oral scrapings in children have been demonstrated. Little is known about subclinical CHPI and about events that up-regulate a latent HPV infection.

HPV is a very common infection and certain subtypes of the virus can lead to cervical cancer, the second most common cancer in women worldwide. The International Agency for Research on Cancer has performed several big case-control studies of cervical cancer in separate nations over the previous 15 years to evaluate the impact of male circumcision on the danger of genital HPV infection in males and the risk of cervical cancer in their sexual partners. “. (Alexander Mckay; 2001)

In the vast majority of patients, cervical cancer originates at the border between the cervix and uterus. As cervical cells undergo a characteristically slow progression of precancerous changes, the pap smear is able to reveal the early phases of such change.

When the Pap smear is examined under the microscope by the pathologist, the earliest change that can be detected is known as carcinoma in situ (CIS). This cellular change is graded on a scale of 1 to 3, with stages 1 and 2 described as dysplastic, meaning the cervical cells are benign but abnormal in that they have lost their normal pattern of organization. CIS 3, however, defines the earliest stage of cervical cancer, because malignant cells are present in the first layer of cells lining the cervix (Woodworth, C., Gaiotti, D., Michael, E., Hansen, L., and Nees, M., 2000).

Whenever malignant or abnormal cells are detected, additional testing is necessary. Unlike the Pap smear, the supplemental procedures of biopsy and conization entail the excision of cervical tissue. The biopsy can generally be conducted at the doctor’s office, but conization, which includes more comprehensive removal of a cone-shaped piece of tissue from the cervix, is typically done under general anesthesia in a hospital operating room. These tests provide adequate tissue samples for the purpose of staging the cancer. If malignant cells have not penetrated into the cervix, the cancer is classified as CIS 3. However, if malignant cells have penetrated below the first layer of the cervix, the cancer is considered invasive.

Cervical Cancer Symptoms

In the earliest and most curable stages, gynecologic cancers produce few symptoms. The symptom most commonly evidenced by cervical and uterine cancers, however, is vaginal bleeding. In contrast to normal menstrual bleeding, cancer -induced bleeding is unpredictable in terms both of frequency and duration. In advanced stages, these cancers can also trigger pelvic pain. Although early-stage ovarian cancers cause virtually no symptoms, late-stage cancers can produce abdominal discomfort or bloating (Nees, M., Geoghegan, J.M., Munson, P., Prabhu, V., Liu, Y., Androphy, E., and Woodworth, C.D. 2000).

Because pure symptoms cannot be relied on to establish early diagnoses in this class of cancers, the routine pelvic examination becomes the essential method of prevention and detection. The gynecologic organs, especially the cervix and uterus, are quite easily and effectively screened for cancer during this procedure.

During a pelvic examination, the physician inserts a smooth tong-like instrument known as a speculum into the vagina in order to push back the vaginal walls so that the cervix can be viewed. The surface of the cervix is then gently touched with a swab in order to obtain a specimen or Pap smear for later analysis under the microscope. The physician then performs a manual examination or palpation of the uterus and ovaries.

The routine pelvic examination is an excellent screening method for uterine and cervical cancer. It is estimated that fully 90% of cervical cancers and approximately 50% of uterine cancers can be detected by this procedure (Sellors, J.W. et al., 2000).

Early cervical cancer is frequently asymptomatic (not causing symptoms). The first sign of the disease is generally an abnormal Pap test outcome in females receiving periodic screening. Symptoms that may occur include the following:

• Abnormal vaginal bleeding (e.g. spotting following sexual intercourse, menstrual bleeding, enhanced menstrual bleeding)
• Abnormal (yellow, odorous) vaginal discharge
• Low back pain
• Painful sexual intercourse (dyspareunia)
• Painful urination (dysuria)

Cervical Cancer Diagnosis

Diagnosis of cervical cancer includes a Papanicolaou test (Pap smear) and pelvic examination. Pap smears are investigated by means of a group of procedures collectively called colposcopy. Colposcopy is pain free.

Another type of biopsy, called endo-cervical curettage (ECC), is often added. This procedure, less painful than cervical biopsies, consists of gently scraping (curetting) the cervical canal, most of which is invisible. Many cancer specialists consider the ECC an essential safeguard against a basic error in diagnosis and treatment: that is, treating a less serious lesion on the outer, visible part of the cervix, unaware that a more serious, even cancerous condition may be lurking an inch higher. The ECC is uncomfortable but rarely painful; most of my patients have found it easier to tolerate than the cervical biopsies (Nees, M., Geoghegan, J., Hyman, T., Frank, S., Miller, L., and Woodworth, C.D., 2001).

All the tissues obtained through biopsy are sent to a pathologist, who has them stained and then examines thin slices, mounted on glass slides, under a microscope. The report should be available to your gynecologist (and to you) within a few days or a week. The delay depends mostly on where the pathologist works, how the biopsies are sent, and how the reports are returned. In order to prevent delays due to reports lost in the mail or otherwise mislaid, a good laboratory will call the gynecologist if cancer is identified.

The terms used in the pathologist’s report are explained in Table 1.1:

Asking for a photocopy of Pap smear and biopsy reports is not routine, but there is no reason why the exact language of the report should not be available to you. It is important to get as much of the information as possible.

TABLE 1.1 Cervical and ECC Biopsy Reports

NORMAL Cervical Biopsy
Normal epithelium	These reports are reassuring. They indicate changes that are not precancerous.
Squamous metaplasia
Chronic cervicitis
Microglandular hyperplasia	Chronic cervicitis is a frequent change, particularly after childbirths. Microglandular hyperplasia is common in birth control pill users.
ABNORMAL Cervical Biopsy
Koilocytosis, HPV	These words and phrases indicate the presence of increasingly worrisome changes. They must be followed up or treated. Continued care (“follow-up”) is needed even after treatment.
Mild dysplasia, CIN I
Moderate, severe dysplasia
CIN II, III, carcinoma in situ
Microinvasive cancer	This is a very early cancer and must be evaluated to determine how widely the cancer has spread. Treatment needed may be less extensive than for frankly invasive cancer.
Invasive cancer: Squamous cancer or adenocarcinoma	Diagnosis is established; proceed to staging to determine treatment: surgery, radiation, chemotherapy, or combinations of these.
ABNORMAL ECC (Endocervical Curettage)
Koilocytosis, HPV	These descriptions may indicate abnormal changes inside the certical canal that may not be apparent by looking. A cone biopsy may be needed.
Dysplasia: mild, moderate, severe
CIN I, II, III, carcinoma in situ
Invasive cancer: squamous or adenocarcinoma	Diagnosis established; proceed to staging and treatment.

Brief Patient Profile

Mrs Smith (name changed for confidentiality) is a 65 year old lady admitted to the gynecology  ward with offensive post-menopausal bleeding. On examination with speculum, she was found to have fungating growth of the cervix. She was sent for examination under anaesthetic and biopsy was taken, which showed a large carcinoma of the cervix occupying the upper vagina and had spread to the uterus. Histologically this was a fairly well differentiated squamous cell carcinoma. The plan was for her to undergo Wertheim’s hysterectomy and bilateral salpingo-oophrectomy followed by radiotherapy and chemotherapy.

Screening

• Pap smear

It is more difficult to talk about the false positive rate for Pap smears because there are two types of abnormal results. First, roughly 10 percent of Pap smears need to be repeated because of inflammatory changes, generally related to infection. Here, age is again an important variable: adolescents have a false positive rate of more than 15 percent, whereas for women over 60 it is less than 5 percent (Adab P, McGhee SM, Yanova J, et al., 2004).

Second, around 5 percent of women undergoing a Pap smear will be told they have a cellular abnormality that is potentially worrisome for cancer. This number also varies by age. Among adolescents the proportion of smears diagnosed with ASCUS (atypical squamous cells of unknown significance) or SIL (squamous intraepithelial lesion) has been reported to be as high as 14 percent. Since almost no women with ASCUS and SIL have or will develop invasive cervical cancer, virtually all of these test results can be considered false positives. However, many of these abnormalities end up being treated, so the problem can also be characterized as unnecessary diagnosis. (Trimble E, Schoenfeldt M., 2003; Trimble E, Schoenfeldt M., 2004)

Four major screening tests—all of which can, and do, render false positive results. In fact, a positive screening test is much more likely to be a false positive than a cancer, generally speaking. So if you receive a worrisome screening test result, just remember: chances are good it is incorrect.

TABLE 1.2 Pap Smear Reports

Language Used	Meaning
Normal	No abnormal cell identified.
Specimen unsatisfactory	Not enough cells or poorly preserved cells— best to repeat Pap smear.
Atypia of known significance	These descriptions indicate that the effects of infection, inflammation, repair process, or aging have been noted. Treatment may be required, but cancer is not suspected.
Reactive or reparative changes
Inflammatory chances
Squamous metaplasia
Atrophy
Trichomonas, Monilia, bacteria, or other organisms noted
Atypia of undetermined significance (ASCUS)	Abnormal cells are present, but not abnormal enough to classify as inflammatory or precancerous. Treatment may be prescribed. Must be investigated by at least a repeat Pap smear in 3-4 months or by colposcopy.
Low-grade squamous cell lesion, HPV, koilocytosis, mild dysplasia, CIN 1 (Cervical Intraepithelial Neoplasia)	Abnormal cells are present and colposcopy with or without biopsy are recommended to confirm diagnosis. Cancer is unlikely. Treatment not absolutely essential because many of these abnormalities disappear spontaneously. Follow-up essential.
Cancer: squamous cell carcinoma or Adenocarcinoma	Colposcopy and biopsy are needed urgently.
Sperm	Recent intercourse, sperm identified.

• Liquid-based cytology

Liquid-based cytology permits deposition of cells onto a thin-layer on a microscope slide; computer-assisted imaging is assisted, as cell overlap and obscuring rubble are moderated. Devices have been developed or anticipated that either recognize slides not entailing cytotechnologist appraisal (sorting), or recognize cells on the slide that value review (computer-assisted screening). These technologies have the prospective to transform cytology, as they can diminish the weariness of the user, permit more glides to be reviewed, lessen the screening error rate, and, with proper decision support, recognize morphologic features that are not perceptible in routine human review. Finally, a benefit of liquid based cell collection is that sample that is not taken for morphologic review can be used for adjunctive molecular examination (Sawaya, G.F. et al. 2000).

• Colposcopy—psychological effects of a positive smear

Abnormal Pap smears are investigated by means of a group of procedures collectively called colposcopy. Colposcopy itself is pain free: A speculum is inserted, the cervix is cleansed with vinegar and is then inspected with a colposcope, which enlarges the cervix eightfold or tenfold, or more if needed. Vinegar (acetic acid) makes abnormal areas easy to identify, and these are next biopsied. A biopsy is a tiny sample of tissue, removed with sharp forceps. This may be pain free or somewhat painful, particularly if the instrument with which the biopsy is taken is not sharp. Depending on how widespread the abnormal area appears, one, or two, or three biopsies may be taken, each as small as a pea. It is rare that three biopsies are not enough and more must be taken. (Trimble E, Schoenfeldt M, Cornelison TL, Wright JJ, Kolker A, Christian M., 2002)

The pain of having a biopsy taken may be lessened by taking a pain medication such as Aleve, Motrin, Anaprox, or Tylenol with codeine half an hour or an hour before the biopsy is taken. Not all gynecologists recommend this simple precaution routinely. If you are exceptionally sensitive to pain, even a tranquilizer may be added or a nerve block given with a small gauge needle. For even more pain relief, intravenous drugs may be used. However, these measures require more than the usual gynecological office and staff, and they are rarely needed. The facilities are usually available, but if you think you will need them, you may have to insist on getting them well before your turn to undergo colposcopy arrives.

Organizational, social and political influences on cervical cancer and its treatments

Social influences play great role in the need of preventive screenings amongst many people. Language also is an obstruction to screening for people belong to different ethnicities. Such as American Asian women, Muslim women etc. moreover, politically governmental organization persuade plans and policies relating to cervical cancer prevention education and intervention. The drug industry reins the cancer field, through their supremacy of almost every single cancer research and treatment foundation. Thousands of top cancer researchers in the world are on the payroll of a dozen drug companies, also these similar drug company executives sit on the Boards of main cancer centers. They as well take over the main oncology organizations. Patients require knowing concerning the dirty politics of the cancer industry.

Organizational influence is that Drug companies proffer doctors pay-offs for enrolling patients in clinical trials. Mergers are going on linking giant pharmaceutical companies. Massive monopolies are being formed which will more limit autonomy of choice for patients.  The UK’s drug assessments body, the National Institute for Health and Clinical Excellence (NICE), has been deeply criticized by numerous charities for the duration of time it takes for the body to propose treatment for NHS use subsequently they have been given a license. NICE has previously pledged to fast track its appraisal of the wider use of the cancer drug.
There are undesirable delays in patients having admittance to cancer drugs which are immediately looking at means to speed up the NICE assessment process. Drugs awaiting a NICE assessment have made it apparent to the NHS that it must not withhold funding for treatments because NICE regulation is not presented.

UK lags behind as it comes to cancer survival rates, expenditure on cancer drugs and access to new cancer treatments. If the government desires the UK to get closer to with Europe in terms of cancer care then they require a new Cancer Plan with new money trailed to ensure it gets through to front-line cancer services. Latest treatments are life and death issues for cancer patients.

Pathology and Spread

• CIN-squamous cells

CIN—usually pronounced “sin” (and the sin is not meant as a reflection on the woman being examined!). CIN is short for “cervical intra-epithelial neoplasia,” which is basically a longer way of saying dysplasia, and CIN can be numbered as 1 (mild), 2 (moderate), or 3 (severe) types.

It is typically recognized that cervical intraepithelial neoplasia (CIN) occurs in a range, from dysplasia and carcinoma in situ (preinvasive lesions) to microinvasive and bluntly invasive cervical cancer. Squamous cell carcinoma is the mainly common type of cervical cancer.

plausible pathophysiologic processes concerned in the expansion of CIN comprise inflammation from vaginal and cervical infections, particularly sexually transmitted infections caused by human papilloma virus and herpesvirus type 2 (HSV-2); rapid metaplasia at the conversion zone of the cervical mucosa, which generates susceptibility of cervical cells at that site; extremely rapid metaplasia throughout pubescence, the age of the majority rapid cellular turnover; ecological revelation to carcinogens, particularly nicotine and other substances in cigarette smoke, and host immunoincompetence.

The conversion zone usually shows metaplasia in the evolution from columnar to squamous cells and is the area most susceptible to carcinogenic influences. Numerous of the risk factors and plausible pathophysiologic instrument of cervical cancer advocate that the transformation zone is the most significant area for cytologic sampling. This zone restrains provisional “genetic disarray,” in which a diversity of abnormal changes take place moderately more often than in areas of even epithelium.

• Metastasis-local &distant

Cancer cells can attack and injure tissues and organs near the tumor. Cancer cells as well can secede from a malignant tumor and pierce the lymph system or the bloodstream. This is how cancer of the cervix can reach to other parts of the body, such as close by lymph nodes, the rectum, the bladder, the bones of the spine, and the lungs. The spread of cancer is called metastasis (Hislop TG, Schwartz SM, Taylor VM, Pineda M, Tu S, Teh C, Jackson JC, Yasui Y, 2000).

Cervical Cancer Staging and Grading

If the cancer is considered invasive, further testing is necessary to determine the degree of spread. Initially, a procedure known as a colposcopy is performed. In this procedure, the cervix is coated with a solution that whitens abnormal areas on contact, thus enabling the physician to examine the suspicious site with a magnifying instrument or colposcope and to perform a more precise biopsy. In addition to routine blood tests, computed tomography (CT) scans, and chest x ray, the patient may also be given a thorough pelvic examination under anesthesia as well as a cystoscopy (examination of the bladder with a lighted flexible tube) and sigmoidoscopy (examination of the rectum with a lighted flexible tube). Based on the results of these tests, the physician employs a set of guidelines known as a staging system to classify the cancer. Stages are described by the International Federation of Gynecology and Obstetrics (FIGO) or the TNM classification of the American Joint Cancer Committee (AJCC).

TNM Classification

TNM staging is a process of determining the extent of malignant disease. This system was developed by oncologists to assist in planning treatment, to provide broad risk categories for estimating prognosis and evaluating treatment response, and to facilitate the exchange of information between physicians concerned with the care of a patient. The system categorizes an individual tumor using a three-variable classification system. The three variables used are known as T, N, and M, where T defines the primary tumor, N the extent of lymph node involvement, and M the presence or absence of distant metastases. the TNM classification system is modified in a way specific to the cancer, and there are many pediatric cancers for which the TNM system is not useful.

TNM definitions

The category T definitions correspond to the several stages FIGO accepts.

Primary tumor (T)

• TX: Primary tumor cannot be assessed
• T0: No evidence of primary tumor
• Tis: Carcinoma in situ

T1/I: Cervical carcinoma restricted to the uterus (corpus expansion should not be taken into account)

T1a/IA: Invasive carcinoma diagnosed only by microscopy. All macroscopically visible lesions–even with superficial invasion–are T1b/IB. Stromal invasion measured from the base of the epithelium with a maximum depth of 5 mm and a horizontal spread of 7 mm or less. The participation of vascular space, venous or lymphatic, has no impact on classification

• T1a1/Ia1: Strom invasion measured in depth of 3 mm or less and in horizontal spread of 7 mm or less
• T1a2/IA2: Measured stromal invasion more than 3 mm and not more than 5 mm with a horizontal spread 7 mm or less

T1b/IB: Clinically noticeable lesion higher than T1a2/IA2 restricted to the cervix or microscopic lesion

• T1b1/IB1: Clinically noticeable lesion with a maximum size of 4 cm or less
• T1b2/IB2: Clinically noticeable lesion with a maximum dimension of more than 4 cm

T2/II: Cervical carcinoma invades the uterus but does not invade the pelvic wall or the reduced vaginal third

• T2a/IIa: Tumor without parametrial involvement
• T2b/IIb: Tumor with parametrial involvement

T3/III: Tumor spreads through the pelvic wall and/or includes the lower third of the vagina and/or triggers hydronephrosis or failure of the kidney

• T3a/IIIA: Tumor includes a lower third of the vagina, no pelvic wall expansion
• T3b/IIIB: Tumor extends to pelvic wall and/or causes hydronephrosis or nonfunctioning kidney

T4/IVA: Tumor invades bladder or rectum mucosa and/or expands beyond the real pelvis (bullous edema is not enough to classify a tumor as T4)

M1/IVB: Distant metastasis

Regional lymph nodes (N)

• NX: Regional lymph nodes cannot be assessed
• N0: No regional lymph node metastasis
• N1: Regional lymph node metastasis

Distant metastasis (M)

• MX: Distant metastasis cannot be assessed
• M0: No distant metastasis
• M1: Distant metastasis
• AJCC stage groupings

Stage 0

Tis, N0, M0

Stage 0 is carcinoma in situ, intraepithelial carcinoma. There is no stromal invasion.

Stage IA1

T1a1, N0, M0

Stage IA2

T1a2, N0, M0

Stage IB1

T1b1, N0, M0

Stage IB2

T1b2, N0, M0

Stage IIA

T2a, N0, M0

Stage IIB

T2b, N0, M0

Stage IIIA

T3a, N0, M0

Stage IIIB

T1, N1, M0

T2, N1, M0

T3a, N1, M0

T3b, any N, M0

Stage IVA

T4, any N, M0

Stage IVB

Any T, any N, M1

FIGO Staging

Stage I is carcinoma strictly confined to the cervix; extension to the uterine corpus should be disregarded.

Stage IA: Invasive cancer identified only microscopically. All gross tumors are phase Ib cancers even with superficial invasion. Invasion is limited to measured stromal invasion with a maximum depth of 5 mm* and no wider than 7 mm.* The invasion depth should not be drawn from the epithelium base by more than 5 mm, either surface or glandular, from which it originates. The involvement of the vascular space, either venous or lymphatic, should not change the stage.

• Stage IA1: Measured stroma invasion not exceeding 3 mm in depth and not exceeding 7 mm in diameter.
• Stage IA2: Measured stroma invasion exceeding 3 mm but not exceeding 5 mm in depth and not exceeding 7 mm in diameter.
• Stage IB: Clinical lesions higher than phase IA restricted to the cervix or preclinical lesions. Stage IB1: Clinical lesions in size not exceeding 4 cm.
• Stage IB2: Clinical lesions in size exceeding 4 cm.

Stage II is a carcinoma extending beyond the cervix but not extending to the pelvic wall. The carcinoma includes the vagina, but not the lower third.

• Stage IIA: No apparent participation in parametries. Involvement of up to the vagina’s top two-thirds.
• Stage IIB: Obvious participation of parameters, but not on the sidewall of the pelvic.

Stage III is a carcinoma that has spread to the sidewall of the pelvic. There is no cancer free space between the tumor and the pelvic sidewall on rectal examination. The tumor includes the vagina’s reduced third. All cases with a hydronephrosis or nonfunctioning kidney should be included, unless they are known to be due to other causes.

• Stage IIIANo extension to the pelvic sidewall, but the lower third of the vagina is involved.
• Stage IIIB: Extension onto the pelvic sidewall or hydronephrosis or nonfunctioning kidney.

Stage IV

• Stage IV is a carcinoma that extends beyond the true pelvis or involves the bladder and/or rectum mucosa clinically.
  • Stage IVA: The tumor is spread over neighboring pelvic organs.
  • Stage IVB: Spread to distant organs.

• In relation to patient

On the basis of Histopathological lab results Mrs Smith classified in Stage T2b/IIb: Tumor with parametrial involvement, N0: : No regional lymph node metastasis and M0: No distant metastasis .

On the basis of Figo patient is in Stage IIA of Cervical Cancer through radiation therapy or radical hysterectomy consequences in cure rates of seventy to eighty percent. The assortment of either option depends on patient issues. The size of the tumor is an imperative predictive factor and must be vigilantly assessed in opting optimal therapy. treatment with high-dose radiation therapy will get local control and survival rates similar to treatment with radiation therapy and hysterectomy. Surgery after radiation therapy might be signified for patient if tumors confined to the cervix which retort moderately to radiation therapy or in whom vaginal structure prevents optimal brachytherapy.

In stage IIA disease found to have poor prognostic factors (metastatic disease in pelvic lymph nodes, parametrial disease, or positive surgical margins) at time of primary surgery. though the positive trials differ somewhat in terms of stage of disease, dosage of radiation, and plan of cisplatin and radiation, they all reveal considerable survival benefit for this shared approach. strong consideration must be given to the incorporation of concurrent cisplatin-based chemotherapy with radiation therapy if this women entail radiation therapy for treatment of cervical cancer.

Cervical Cancer Treatment

HPV Vaccine

The villain of cervical cancer is the human papillomavirus ( HPV ), the cause of genital or venereal warts as well as cervical cancer. The process that leads to cancer begins in women who became sexually active at an early age, with the papillomavirus finding an easy entry into the mucosa, the delicate skin like covering of the cervix. The source of the virus is the skin covering the penis of an affected male, and the virus is picked up by women during intercourse without condoms. In teenage boys, who are often the silent carriers of the virus, the skin may look perfectly normal. Even years later, it may require using a magnifying glass (or a colposcope) on the skin of the penis to reveal the tiny bumps and telltale plaques that signal the presence of the virus. Such skin is surreptitiously shedding HPV, infecting cervical cells. Acquiring such an infection may also occur years later, but the sequence that ultimately leads to cervical cancer often seems to start in the relatively immature cervical cells of teenagers.

Years before cancer appears, the cells that make up the surface of the cervix begin to develop changes described as premalignant or precancerous. These go by a variety of names and abbreviations: dysplasia, low-grade and high-grade CIN (cervical intraepithelial neoplasia), carcinoma in situ, and SIL (squamous intraepithelial lesion) are all terms in recent or current use (Basu, P. et al., 2002). More important, some of the earliest precancerous changes are mild and may disappear with simple medical measures such as the treatment of vaginal and cervical infections with antibiotics or the consistent use of condoms for six to nine months. These treatments rely on a balance between the damage caused by repeated exposure to the papillomavirus, and a normally functioning immune system, which destroys abnormal cells, hastening healing. Unfortunately, there is no guarantee that healing will be complete. Also, the more advanced the cervical disease, the less likely it is to retreat to a lesser grade of severity or to disappear. The recent epidemic of infections with HPV has made cancer specialists very cautious about undertaking unaggressive treatment plans. Faced with a potentially lethal process, few women (and even fewer gynecologists) will choose an option that calls for years of observation with colposcopies and biopsies without definitive, virtually guaranteed-to-succeed treatment.

Cervical cancer has been known for decades to be a venereal disease, one associated with intercourse at an early age and with multiple partners. Catholic nuns, for example, do not get cervical cancer; reportedly, only one nun ever developed cervical cancer, and she ultimately revealed that before becoming a nun, she was very promiscuous. This story might be apocryphal, but such ideas should not be discussed with women who have recently been found to have cervical cancer or its precursors. They are upset enough without the guilt and self-blame such information causes, and the theories add nothing to effective care. (Thomas DB et al., 2002)

Older studies indicated that cancer is more likely to develop in women who are married to men whose previous wives developed cervical cancer. This implied an infectious agent, spread from men to women, although, of course, the virus also passes from women to men (Hasenyager C., 1999). More recently, certain strains within the large family of papilloma viruses have been implicated. Laboratory tests are available to identify which strain, if any, might be multiplying in a woman’s cervical cells, but these tests have not achieved much acceptance among gynecologists. However, these strains appear to be able to damage the chromosomes of cervical cells more rapidly than previously thought possible. This bears a certain resemblance to the transmission of AIDS. In both cases, intimate contact, sexual or other, is required. Years after what may have been a brief relationship (or even a one-night affair), the virus may surface and cause the development of lethal diseases. Condoms may not offer perfect contraception or guaranteed protection against venereal diseases, including cervical cancer and AIDS, but they are simple and effective measures and are highly recommended.

As HPV infects the cervix, millions of viruses lodge in sheets of cervical cells, and the chromosomal material in these cells begin to undergo a drastic change. Layers of cells that used to grow in an orderly fashion now begin to grow abnormally and at an accelerated pace. Previously they adhered to each other; now they break away from each other. As long as these changes are confined to the surface of mucosal skin, the illness is localized and treatable in your gynecologist’s office. This is true even for the most advanced form, which is often referred to as carcinoma in situ: a localized, noninvasive form of cancer. Perhaps it should be called “not-yet invasive- cancer”: If not treated, the cells begin to push against the basement membrane, a strong, leathery sheet of cells in the skin covering the cervix, and in due course they penetrate it. This event resembles a small group of rowdy hooligans breaking through a solid barrier, followed by a crowd, spreading out and causing mayhem.

Similarly, with the basement membrane penetrated, cancerous cells begin to stream into surrounding tissues. This crucial and potentially deadly event is signified by the word “invasive.” (Thomas DB et al., 2001).The malignant cells have broken through; they have escaped from their original site and are now ranging further into new locations. They may be picked up by the lymphatic system, vessels that slowly sweep lymphatic fluid and cancerous cells toward nearby lymph glands. Some weeks or months later, these glands can no longer contain the spread of the cells, and as they allow the malignant cells to pass through, lymph glands further away are invaded. From the cervix, this process usually takes many months to become widespread, although in other sites (for instance, in the ovary) a much faster rate of spread occurs. The cancerous cells soon range so widely that it may no longer be possible to remove them all, even by cutting out large blocks of tissue such as the entire uterus. Such a cancer was initially operable, but it can no longer be excised completely. This explains the need for additional treatments such as chemotherapy, radiation, or one of the more experimental immunotherapies (Thomas DB et al., 2001).

Cervical Cancer Surgical Treatment

The treatment of cervical cancer is dependent on the stage of the cancer and the overall medical condition of the patient, as well as the patient’s wishes concerning her reproductive capacity. The following is a synopsis of treatments by stage.

• Carcinoma in situ (Stage 0). Localized surgery, aimed at eradicating the focus of the cancer, is extremely curative for this stage. Such surgery includes the conization as well as cryosurgery and laser surgery. Cryosurgery employs a freezing technique to destroy cancer cells, whereas laser surgery utilizes a powerful narrow beam of light. In order to ensure that the cancer does not recur, such patients must have Pap smears every 4 to 6 months after surgery. Although the benefit of all conservative surgery is that fertility is preserved, women with CIS who no longer desire to maintain their fertility may elect hysterectomy.
• Stage I. Either hysterectomy or local radiation therapy (RT) is curative for the earliest phases of this stage. (Radiation therapy, the treatment of cancer with powerful x rays) However, if the cancer penetrates more than 3 mm of cervical tissue, the patient must be treated with either a radical hysterectomy or RT of the cervix and pelvic lymph nodes.
• Stage II. Although this stage is treated with either RT or radical

hysterectomy, the lymph nodes of the pelvis is always routinely treated with RT. Generally, RT is used as the primary treatment in more extensive cancers.

Stage III. This stage is treated with RT. Surgery is performed for diagnostic purposes. The role of chemotherapy is presently being evaluated.

Stage IV. This stage can be treated with RT, surgery, or chemotherapy, with the choice of therapy depending on the extent of disease.

Radical/Adjuvant chemotherapy & radiotherapy- side effects and Palliative

Cervical cancer is usually preventable. Once abnormalities appear, years may pass before cancer appears. Modern treatments have largely replaced older procedures such as conization of the cervix (the removal of a small, cone-shaped piece of the cervix) and prophylactic hysterectomy. The new treatments are usually less extensive and less expensive and are easier to accept. Amazingly, almost any treatment that eliminates the area in which abnormalities are developing is very likely to cure the illness, and this is true as long as cancer has not developed. The gynecologist’s job is fairly easy: Make sure how severe the disease is, pinpoint all the sites involved, and arrange treatment. (Moreno Vet al., 2002)

Simple electrocautery was the oldest treatment, but it has been abandoned in the United States, because electrocautery burned away tissue, which could not be examined under a microscope by a pathologist. Electrocautery was superseded by conization, which allowed for careful microscopic examination, an important step in distinguishing cancer from less serious conditions.

Conization has also become largely obsolete. It is still used if there is some unusual feature that calls for it—for instance, ominous Pap reports from women whose colposcopy and biopsies are inconclusive. Disease high in the cervical canal, as shown by the ECC procedure, is another good reason for conization. Conization may, however, damage the cervix for future childbearing. If the accent is on preserving reproductive function, conization should be avoided as much as possible. If the accent is on making absolutely certain that there is no cancer, conizations will continue to be done. Large clinics whose patients do not always return for continued care are more apt to offer a procedure that not only diagnoses precisely but often cures the disease being investigated.

Cryosurgery consists of freezing the cervix with a specially designed probe, cooled with liquid nitrogen. Freezing works because it destroys tissue just as much as heating it with electricity does. This is an outpatient procedure, minimally painful, relatively inexpensive, and successful about 90 percent of the time. If it does not work, another session of cryosurgery may solve the problem, and other treatments remain available. After frozen tissues thaw, cryosurgery is followed by about ten days of a profuse, watery discharge that is best managed with sanitary pads rather than tampons. (Munoz N et al., 2002)

Laser surgery is substantially more expensive than other treatments, with roughly similar rates of cure. It is better for larger and multiple lesions and may cause less scarring than either conization or freezing the cervix (cryosurgery).

The latest innovation is the use of improved electrosurgical methods called LEEP (for loop electric excision procedure) or LLEETZ (for large loop electric excision of the transformation zone, the area in which most precancerous lesions appear). Early reports indicate that these procedures offer substantial improvements over previous methods. If there is no disease higher up in the cervical canal, as shown by a negative ECC, all the remaining work can be combined into one efficient office procedure, performed under local anesthesia.

Hysterectomy has a very limited place in the care of women with these lesions. If you have any condition short of cancer, lesser procedures should be curative. If invasive cancer is found, there is a chance that the disease is no longer confined to the cervix. Therefore, more extensive treatments are needed: radiation, a radical hysterectomy, chemotherapy, or combined treatments. In this case, simple hysterectomy (in contrast to radical hysterectomy) is not advised because results are poor.

There is one small group of patients for whom hysterectomy is appropriate. If the cervical biopsy diagnosis is microinvasive cancer, the cancer has broken through the basement membrane very recently, but in all likelihood it has not spread far. Micro invasion is defined as invasion less than 3 millimeters deep from the basement membrane. A conization procedure should now be performed to be sure that there is not deeper penetration in another, nearby patch of micro invasion. If there is not, simple hysterectomy is reasonable treatment, with excellent chances of a cure. Once cancer has spread deeper, lymph nodes may be involved, necessitating radical hysterectomy, radiation, or a combination of these.

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Multi-disciplinary team

Cancer therapy might comprise one or more treatment modalities delivered concomitantly or sequentially including surgery, radiation, chemotherapy, and/or biologic therapy. This is referred to as multidisciplinary care. The multidisciplinary approach to cancer treatment and the resultant medical team is a notion to the majority individuals who are used to simply seeing a family doctor or common practitioner. As a cancer patient, treatment might need an entire medical team as the steps of cancer treatment are beyond the scope of a single doctor. additionally, the methods of real treatment delivery are diverse, needing diverse specialty doctors. (Skegg DCG, 2002)

In relation to my specific patient

As, Mrs Smith was sent for examination under anaesthetic and biopsy was taken, which showed a large carcinoma of the cervix occupying the upper vagina and had spread to the uterus. Histologically this was a fairly well differentiated squamous cell carcinoma. The plan was for her to undergo Wertheim’s hysterectomy and bilateral salpingo-oophrectomy followed by radiotherapy and chemotherapy.

• Prognosis

Regular screening has enabled women with pre cancerous changes and early stage cervical cancers to be picked up and treated early (Castellsague, X. et al. 2002).  Of all those women diagnosed with cancer of the cervix, about 7 out of 10 women on average (70%) will be alive 5 years after diagnosis.  Younger women’s survival rates are better than older women. This is at least partially because previous diagnosis of the disease in younger females tends to occur.

• In relation to patient

As, Mrs Smith has a large carcinoma of the cervix occupying the upper vagina and had spread to the uterus. It is stage 2 where the survival statistics fall with the more advanced stages of cervical cancer.  Between 3 and 5 out of 10 women on average live at least five years after a diagnosis of stage 3 cervical cancer.

Conclusion

• Evaluate Screening Programme

The smear test was initiated in Britain in the mid sixties. In the late eighties, following criticisms of the random character of the cervical smear system, a National Coordinating Network for the NHS Cervical Screening Programme was instituted. In nineties the new indenture forced on GPs by the government presented considerable incentives, currently worth approximately £65 million a year, joined to smear rate performance targets. As a consequence of these measures, reporting of the target age group raised from forty percent in 1988 to 85 percent in 1994, a level consequently continued. in women under fifty ‘screening might have barred 800 deaths in 1997’ was challenged by critics who noted that the data offered could evenly well hold up the conclusion that screening caused a comparable raise in mortality. The distinction between the high level of public reliance in the cervical smear programme as well as the private gratitude amongst medical authorities of its inadequate character is amazing.

The NHS Cervical Screening Program aims at reducing the amount of females living with cervical cancer and the number of females dying from the disease. Being invited for cervical screening doesn’t mean you’re particularly at risk from cervical cancer – all women aged 25 to 64 is invited.

• Implications for practice- health promotion

Averting cervical cancer has massive benefits not simply for women’s health, but also for the comfort of families and communities. Very frequently, cervical cancer is not measured a precedence as it is perceived as a disease of adult and older women, who might be measured unproductive members of households and societies. This misperception, collective with staid competing demands for health resources, frequently means that the health desires of middle-aged and older women are disregarded. Thus far, women have a considerable influence on family welfare all through their lives.

Cervical screening affords women through the opportunity to get control of their cervical health, although women persist to under exploit this health service. prelude analyses from this research divulges that females might not be aware of issues surrounding cervical cancer such as risk factors, cause, etc to recognize and engage in the proper cervical screening practices. Additionally the need for women to be optimistic to feel like partners in health management. Through the initiation of Screening Program, screening might get better within years to come; though, tracking adolescent women longitudinally is reasonable to establish the efficiency of these programs.

Also Study:

The Availability of Family Support to Breast Cancer Patients

Experiences of Patients For Cancer Diagnosis

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• https://www.aafp.org/afp/20000301/1369.html