There are two types of cells on the cervix's surface: squamous and columnar.

Most cervical cancers are from squamous cells. Risk factors for cervical cancer include:

Having sex at an early age Multiple sexual partners Poor economic status (may not be able to afford regular Pap smears) Sexual partners who have multiple partners or who participate in high-risk sexual activities Women whose mothers took the drug DES (diethylstilbestrol) during pregnancy in the early 1960s to prevent miscarriage Weakened immune system

Symptoms
Most of the time, early cervical cancer has no symptoms. Symptoms that may occur can include:

Abnormal vaginal bleeding between periods, after intercourse, or after menopause Any bleeding after menopause Continuous vaginal discharge, which may be pale, watery, pink, brown, bloody, or foul-smelling Periods become heavier and last longer than usual

Symptoms of advanced cervical cancer may include:

Back pain Bone fractures Fatigue Heavy bleeding from the vagina Leaking of urine or feces from the vagina Leg pain Loss of appetite Pelvic pain Single swollen leg Weight loss

Reference: A.D.A.M. Medical Encyclopedia. 2011.

Causes and risk factors for cervical cancer have been identified and include human papillomavirus (HPV) infection, having many sexual partners, smoking, taking birth control pills, and engaging in early sexual contact.

What is the cervix?

The cervix is part of a woman's reproductive system. It's in the pelvis. The cervix is the lower, narrow part of the uterus (womb). The cervix is a passageway:

The cervix connects the uterus to the vagina. During a menstrual period, blood flows from the uterus through the cervix into the vagina. The vagina leads to the outside of the body.

The cervix makes mucus. During sex, mucus helps sperm move from the vagina through the cervix into the uterus.

During pregnancy, the cervix is tightly closed to help keep the baby inside the uterus. During childbirth, the cervix opens to allow the baby to pass through the vagina.

What is cancer?
Cancer begins in cells, the building blocks that make up tissues. Tissues make up the organs of the body. Normal cells grow and divide to form new cells as the body needs them. When normal cells grow old or get damaged, they die, and new cells take their place. Sometimes, this process goes wrong. New cells form when the body does not need them, and old or damaged cells do not die as they should. The buildup of extra cells often forms a mass of tissue called a growth or tumor. Growths on the cervix can be benign or malignant. Benign growths are not cancer. They are not as harmful as malignant growths (cancer).

Benign growths (polyps, cysts, or genital warts):

are rarely a threat to life

don't invade the tissues around them

Malignant growths (cervical cancer):

may sometimes be a threat to life

can invade nearby tissues and organs

can spread to other parts of the body

Cervical cancer begins in cells on the surface of the cervix. Over time, the cervical cancer can invade more deeply into the cervix and nearby tissues. The cancer cells can spread by breaking away from the original (primary) tumor. They enter blood vessels or lymph vessels, which branch into all the tissues of the body. The cancer cells may attach to other tissues and grow to form new tumors that may damage those tissues. The spread of cancer is called metastasis.

Risk factors:
HPV infection: HPV is a group of viruses that can infect the cervix. An HPV infection that doesn't go away can cause cervical cancer in some women. HPV is the cause of nearly all cervical cancers. HPV infections are very common. These viruses are passed from person to person through sexual contact. Most adults have been infected with HPV at some time in their lives, but most infections clear up on their own. Some types of HPV can cause changes to cells in the cervix. If these changes are found early, cervical cancer can be prevented by removing or killing the changed cells before they can become cancer cells. The NCI fact sheet Human Papillomaviruses and Cancer: Questions and Answers has more information. A vaccine for females ages 9 to 26 protects against two types of HPV infection that cause cervical cancer. The NCI fact sheet Human Papillomavirus (HPV) Vaccines: Questions and Answers has more information.

Weakened immune system (the body's natural defense system): Infection with HIV (the virus that causes AIDS) or taking drugs that suppress the immune system increases the risk of cervical cancer.

Sexual history: Women who have had many sexual partners have a higher risk of developing cervical cancer. Also, a woman who has had sex with a man who has had many sexual partners may be at higher risk of developing cervical cancer. In both cases, the risk of developing cervical cancer is higher because these women have a higher risk of HPV infection.

Using birth control pills for a long time: Using birth control pills for a long time (5 or more years) may slightly increase the risk of cervical cancer among women with HPV infection. However, the risk decreases quickly when women stop using birth control pills.

Having many children: Studies suggest that giving birth to many children (5 or more) may slightly increase the risk of cervical cancer among women with HPV infection.

The stage is based on where cancer is found. These are the stages of invasive cervical cancer:

Stage I: The tumor has invaded the cervix beneath the top layer of cells. Cancer cells are found only in the cervix.

Stage II: The tumor extends to the upper part of the vagina. It may extend beyond the cervix into nearby tissues toward the pelvic wall (the lining of the part of the body between the hips). The tumor does not invade the lower third of the vagina or the pelvic wall.

Stage III: The tumor extends to the lower part of the vagina. It may also have invaded the pelvic wall. If the tumor blocks the flow of urine, one or both kidneys may not be working well.

Stage IV: The tumor invades the bladder or rectum. Or the cancer has spread to other parts of the body.

Recurrent cancer: The cancer was treated, but has returned after a period of time during which it could not be detected. The cancer may show up again in the cervix or in other parts of the body.

Reference: www.medicine.net. 2011

Incidence, pathophysiology and treatment of cervical cancer

2 November, 2004
VOL: 100, ISSUE: 44, PAGE NO: 38 Ruth Dunleavey, BSc, RGN, is clinical nurse specialist, St Vincent's Hospital, Sydney, Australia

Presentation and risk factors The cervix is the inferior part of the uterus, which protrudes into the vagina. It is characterised by two types of epithelium: the endocervical epithelium lines the uterus and superior part of the cervix, while the squamous epithelium is located distal to the endocervical epithelium. The two cell types meet in a region known as the transformation zone, where most cellular abnormalities arise. Cervical cancer can develop from the squamous cells or endocervical epithelium, but squamous cell carcinomas are the most common and account for 85-90 per cent of cervical malignancies (Wright, 2001). The mean age of presentation is 54 years, although intraepithelial lesions are often diagnosed at a much earlier age suggesting long latency between cellular abnormality and malignancy (Cannistra and Niloff, 1996). The most common presenting symptom of cervical cancer is abnormal bleeding, perhaps between periods, after intercourse or postmenopause. This may be accompanied by offensive vaginal discharge. Risk factors include (Cannistra and Niloff, 1996): - Intercourse at an early age;

- Multiple sexual partners (or a sexual relationship with a man who has had multiple partners); - Smoking; - Immunosuppression. Women who present before the cancer becomes too advanced have the best prognosis; cervical screening is effective because cervical neoplasia has a long preinvasive phase (Goodman and Wilbur, 2003). Abnormal cytological specimens Abnormal specimens from cervical smears are defined as: - High-grade squamous intraepithelial lesions (HGSIL); - Low-grade squamous intraepithelial lesions (LGSIL); - Abnormal squamous cells of uncertain significance (ASC-US). The most common abnormal Pap smear finding is ASC-US, which accounts for 5-10 per cent of all smears (Choma, 2003; Goodman and Wilbur, 2003). On further investigation many women with ASC-US have no significant pathology. In such cases the abnormality may be caused by a condition that mimics cervical dysplasia, such as: - Cellular changes due to tissue damage caused by infection, trauma or radiation; - Physiological changes secondary to hormonal use and menopausal status; - A wide range of artefacts resulting from preparation of the specimen (Goodman and Wilbur, 2003). Seventy per cent of ASC-US and low-grade lesions resolve spontaneously (Kubovchik, 2004). However, LGSIL or HGSIL warrant further investigation, generally by colposcopy and biopsy. In colposcopy the cervix is imaged and acetic acid applied to highlight abnormal epithelium. After application of acetic acid, abnormal tissue becomes whitened (Fig 1). Generally the more severe the whitening, the more severe the lesion. Where the edges of the lesion are clearly defined, significant disease is more likely. Where the edges are fuzzy the changes are often precipitated by viral change (Smith, 2000). Cervical intraepithelial neoplasia Usually a colposcopy performed after an abnormal smear will reveal a lesion from which a biopsy can be taken. Biopsies are graded using the cervical intraepithelial neoplasia (CIN) histological grading system, which quantifies degree of cellular dysplasia ranking from CIN I for mild dysplasia to III for advanced dysplasia (Box 1). Most women with LGSIL have CIN I disease. This generally requires no further treatment because 90 per cent of CIN I abnormalities will not progress (Cooper et al, 2003). These women are followed up with repeat smears and possibly colposcopy (Cannistra and Niloff, 1996). CIN II or III disease will be present in 5-10

per cent of women with LGSIL. Women with HGSIL have a 70-75 per cent chance of a CIN II or III lesion and a 1-2 per cent chance of invasive cervical cancer (Wright et al, 2002). Human papilloma virus Almost all cervical cancers contain traces of the human papilloma virus (HPV), which is also causative in the cellular changes that bring about ASC-US, LGSILs and HGSILs. It is thought to infect basal cells within the cervical epithelium gaining access via minor trauma, or at the squamocolumnar junction (Cooper et al, 2003). There are two sub-types of HPV: - Low risk - associated with cutaneous infection (such as warts) (HPV 6, 11, 40, 42, 43, 44); - High risk - associated with infections of the genital tract (HPV 16, 18, 31, 33, 35, 45); HPV 16, 18, 31 and 45 account for about 80 per cent of cervical cancers (Choma, 2003). About 75 per cent of people of reproductive age have been infected with HPV (Choma, 2003). Primary infection occurs mostly in young adults, and a large percentage of people will be infected by the age of 30 (Helmerhorst and Meijer, 2002). The most important risk factor for the acquisition of HPV is number of sexual partners. HPV infection is mainly asymptomatic and transient. Only 20 per cent of people develop premalignant lesions and only a small percentage of these will become cancerous. Ninety per cent of infections resolve completely within two years without identification of clinically significant lesions (Choma, 2003). It is unclear if the virus is eradicated or merely suppressed to undetectable levels. Total abstinence from sex is the only way to prevent HPV infection. Condoms offer some protection, but not if lesions remain uncovered. Also HPV can lie dormant for some time before any symptoms become apparent. It is because of this association with HPV that cervical cancer is sometimes referred to as a sexually transmitted disease. However, while HPV is sexually transmitted, the mechanism whereby a malignancy develops is not. The event that transforms a transient infection into cellular dysplasia or cancer is not fully understood. Integration of HPV into the cell genome is considered an important step in the process (Cooper et al, 2003). The immune status is probably a significant factor. Thus a failure in immunosurveillance - perhaps an expression of genetic defect - is just as likely as lifestyle to be responsible. In recent years it has been recognised that HPV testing may be of significance in the management of low-grade lesions and ASC-US. A positive HPV test with highrisk viral variants suggests more aggressive follow-up is warranted than if the virus is absent or is one of the low-grade strains. The US National Cancer Institute recently sponsored a large study in which an HPV test was found to be as effective as repeat cervical smears for the management of women with ASC-US. This is now

recommended by the American Society for Colposcopy and Cervical Pathology (Solomon et al, 2001), but has not been endorsed in the UK. Reference: www.nursingtimes.net

Cancer of the cervix occurs most often in women over the age of 40. Screening for cervical cancer should begin approximately 3 years after a woman begins to have sexual intercourse. Women who are not sexually active still need to start getting screened for cervical cancer by the time they are 21. Reference: understandingrisk.cancer.gov

FIGO Staging for Cervical Cancer Stage Definition

Preinvasive disease (carcinoma in situ)

Carcinoma strictly confined to the cervix

II

Carcinoma that extends into the parametrium (but not onto the pelvic sidewall) or the upper two thirds of the vagina

III

Carcinoma that has extended onto the pelvic sidewall or involves the lower one third of the vagina. All cases with a hydronephrosis or nonfunctioning kidney should be included, unless they are known to be due to other causes.

IV

Carcinoma that has extended beyond the true pelvis to distant organs or has clinically involved the mucosa of the bladder, rectum, or both

FIGO, International Federation of Gynecology and Obstetrics.

Treatment
Treatment and prognosis of cervical cancer are greatly affected by the extent of disease at the time of diagnosis.

Stage 0 Disease (Carcinoma in Situ)

Invasive cervical carcinoma must be excluded with confidence before therapy for preinvasive disease is undertaken. Standard treatment options include excisional and ablative therapy. In general, excisional therapies are preferred because they are associated with a lower failure rate and provide tissue for histologic evaluation to assess margins and exclude invasion. Excisional therapies include the loop electrosurgical excision procedure (LEEP), laser

conization, cold knife conization, and extrafascial hysterectomy. Ablative therapies include cryotherapy and laser ablation therapy.
6

In most cases, outpatient LEEP is preferred. LEEP uses a fine wire loop with electrical energy flowing through it to remove the transformation zone of the cervix or focal areas of dysplasia. It can quickly and easily be performed in an office setting and generally requires only local anesthesia, thus avoiding the risks associated with general anesthesia. Cold knife or laser conization require general anesthesia.

Stage Ia1 (Microinvasive Cervical Cancer)

Cervical cancer in its earliest stages of invasion is termed microinvasive carcinoma. It is defined as invasion of the stroma no greater than 3 mm deep and no wider than 7 mm in diameter with no lymph-vascular space involvement.

Disease meeting this strictly defined criteria has a very limited risk for lymphatic metastasis, and outcome is excellent with less-radical therapies. Expert pathology review is essential when considering less radical therapies for disease qualifying as microinvasive. Equivalent treatment options include extrafascial hysterectomy, cervical conization, and intracavitary radiation alone (without external beam radiotherapy).

All Other Stage I and Stage IIa Disease

Risk for lymphatic metastasis is increased with larger and more deeply invasive lesions. For this reason, radical therapies are necessary, and referral to a qualified gynecologic oncologist is appropriate and recommended.

Therapy selection depends on patient factors, tumor factors, and surgical expertise. Radical hysterectomy with bilateral pelvic lymphadenectomy is one option; combined external beam radiotherapy and brachytherapy with concurrent chemotherapy is an equivalent option.

Several randomized phase III trials have shown an overall survival advantage for cisplatin-based therapy given concurrently with radiation therapy. As a result of these findings, the National Cancer Institute issued a clinical announcement suggesting that strong consideration should be given to the incorporation of concurrent cisplatinbased chemotherapy with radiation therapy in women who require radiation therapy for treatment of cervical cancer.
7

Stages IIb to IVa Disease

With tumor spread beyond the cervix and upper vagina, cure rates for radical surgery decline. Stages IIb to IVa cervical cancer are best treated by radiation therapy using combined external beam pelvic radiation and concurrent cisplatin-based chemotherapy with intracavitary brachytherapy or interstitial therapy.

Stage IVb Disease

Patients with distant metastasis are no longer amenable to cure by radiation therapy. Unfortunately, response rates to standard chemotherapy are generally less than 20% and are typically brief. All patients with distant metastasis or

recurrent disease should be considered appropriate candidates for phases I and II clinical trials investigating new treatments.

Palliative treatment options include radiation therapy to relieve pelvic disease and chemotherapy with agents such as cisplatin, ifosfamide, paclitaxel, gemcitabine, and irinotecan.
8

Outcomes
If not diagnosed in its early stages, cervical cancer carries high mortality (Table 6). Properly diagnosed and managed, tumor control of in situ cervical carcinoma should be nearly 100%. Table 6: Cervical Carcinoma: 5-Year Relative Survival Rate Disease Extent Survival (%)

All stages

84

Localized

96

Regional

66

Distant

27

Adapted from Ries LAG, Kosary CL, Hankey BF, et al (eds): SEER Cancer Statistics Review, 1973-1995. Bethesda, National Cancer Institute, 1998.

Reference: http://www.clevelandclinicmeded.com. Cleveland Clinic Foundation. 2011.

Pathophysiology
Invasive cervical cancer develops from a preinvasive state termed cervical intraepithelial neoplasia (CIN). CIN 1 represents mild dysplasia and is now classified as low-grade squamous intraepithelial lesions (LSILs), CINs 2 and 3 encompass moderate-to-severe dysplasia and are classified as high-grade squamous intraepithelial lesions (HSILs) based on the Bethesda cervical cytology reporting system. Most LSILs spontaneously resolve, whereas high-grade squamous intraepithelial lesions (HSILs) are more likely to progress to invasive cervical cancer. HSILs are typically detected at an average of 10 to 15 years younger than for invasive cervical cancer. For example, the typical age range for diagnosis of carcinoma in situ is 25 to 35 years, whereas that for invasive cancer is older than 40 years.
6 5

Infection of the cervical epithelium with oncogenic types of human papillomavirus (HPV) is essential to the development of cervical cancer and its precursor lesions (Fig. 1).
7,8

Early epidemiologic studies found that at least

76% of cases of CIN could be attributed to HPV infection. Women with CIN lesions in the study exhibited the typical epidemiologic profile of sexually transmitted infection: more sexual partners, earlier age at first sexual intercourse, and lower socioeconomic status.

Figure 1: Click to Enlarge Evidence supporting the association between infection by carcinogenic HPVs and the subsequent development of virtually all cervical cancer is conclusive. Cervical squamous intraepithelial lesions demonstrate the classic morphologic changes of HPV infection, such as epithelial hyperplasia (acanthosis) and degenerative cytoplasmic vacuolization (koilocytosis) in terminally differentiated keratinocytes with atypical nuclei. HPV has been observed in these lesions using electron microscopy. In addition, HPV structural proteins have been detected in surgical specimens using immunohistochemical staining with antibodies that specifically detect HPV viral antigens. Large serial studies from 22 countries have shown that more than 90% of cervical squamous cell carcinomas contain DNA from high-risk HPV types, presumably transmitted during sexual activity. A more recent study indicated the worldwide HPV prevalence in cervical cancer is as high as 99.7%. Furthermore, HPV DNA has been extracted from metastatic cervical cancer tissues and cervical cancer tumor cell lines in culture.
14,15 7 13 12 11 10

Eighty types of HPV have been sequenced, and approximately 30 of these infect the female and male genital tracts. Eighteen genital HPV subtypes (16, 18, 26, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66, 68, 73, and 82) are classified as high risk because of their close causative association with cervical cancer.
17 16

Research in the last decade has provided a better understanding of the molecular carcinogenesis of HPV. In vitro infection of human epithelial cells by carcinogenic HPV subtypes induces indefinite cell growth, or cell immortalization.
18,19

Two HPV viral proteins, E6 and E7 proteins, are required for cell immortalization.

20-22

Further studies

23-25

revealed that E6 proteins from high-risk HPV interact with the cellular tumor suppressor protein

p53. The p53 suppresses cell proliferation by arresting growth in the G1 phase of the cell cycle. E6 proteins from high-risk HPV complexes with p53 and results in the rapid proteolytic degradation of p53 proteins.
25 23,24

The decreased

level of p53 protein abolishes the cell's ability to suppress uncontrolled cell proliferation. On the other hand, E7 proteins from high-risk HPV bind to another cellular tumor suppressor, the retinoblastoma protein (pRB), and disrupt the complex between the cellular transcription factors E2F-1 and pRB. The free E2F-1 stimulates cellular DNA synthesis and uncontrolled cell proliferation. E6 and E7 proteins from HPV-16 can also cooperate to induce centrosome-related mitotic defects and genomic instability. It is clear that persistent infection by oncogenic HPVs is a prerequisite for the development of cervical cancer and its precursor lesions, although only a few women infected with HPV eventually develop cervical cancer.
27 26

SYMPTOMS There may be no symptoms of a very early cervical cancer, but by the time it is large enough to detect visually it is usually symptomatic with abnormal bleeding. Often this abnormal bleeding occurs after sexual intercourse. Cancers must make new blood vessels as they grow. These new blood vessels are often abnormal and break easily which is why bleeding is a sign of cancer. The cancer also outgrows some of its blood supply, so portions of it are deficient in oxygen. This causes some of the cells to die and for the tissue to become infected. In the cervix this causes a watery or foul discharge that will be noticeable and resistant to most treatments for the usual vaginal infections. As the cancer increases in size it usually grows laterally toward the pelvic wall. The tubes from the kidneys (ureters) that bring urine to the bladder pass through this area and they are easily obstructed. If that happens to both of the ureters, then this will result in renal failure, coma and death. If the cancer grows into the pelvic wall it will press on the nerves that go to the leg and cause unremitting leg pain. These are symptoms of an advanced cancer. Premalignant changes have no symptoms and are usually not noticeable on visual examination. Cervical cancers usually do not spread early. They tend to be slow growing and cause most of their problems in the pelvis. Although distant metastases occur they are usually late events. Cervical cancers can spread by way of the lymphatic system. The lymphatic vessels drain from the cervix to clusters of lymph glands along the pelvic wall. The lymphatics follow the large blood vessels so the route of drainage is upward along the pelvic wall, then along the midline of the backbone and then to the chest. If the pelvic lymph nodes on one side of the pelvis become obstructed with cancer then that will cause swelling in the leg on that side. This is another sign of advanced cancer. STAGING Whenever a cancer is diagnosed the next step is staging. This is a determination of the extent of the cancer. For cervical cancer this is determined by physical examination, chest x-ray, kidney x-rays and looking inside the bladder and rectum. CT scans and MRI scans can be done but they are not used to assign a stage. Likewise, surgical exploration is not used to assign a clinical stage.
CLINICAL STAGES OF CANCER OF THE CERVIX Stage I IA IA1 Cancer confined to the cervix Invasive cancer detectable microscopically only Invasion less than 3 mm and width less than 7 mm

IA2 IB IB1 IB2 Stage II IIA IIB Stage III IIIA IIIB Stage IV IVA IVB

Invasion more than 3 mm but less than 5 mm All others, any visible cancer Cervix less than 4 cm in diameter Cervix greater than 4 cm Spread to adjacent structures Spread onto the vagina Spread laterally toward the pelvic wall More extensive but still within the pelvis Extends to the lower vagina Extends onto the pelvic wall, obstructed ureter Distant spread or involvement of a pelvic organ Involves the inside of the bladder or rectum Distant metastases, i.e. lung, liver or bone

William M. Rich, M.D. Clinical Professor of Obstetrics and Gynecology University of California, San Francisco Director of Gynecologic Oncology University Medical Center Fresno, California
Reference: www.gyncancer.com.

Pathology CIN is graded as 1 (mild cervical dysplasia), 2 (moderate dysplasia), or 3 (severe dysplasia and carcinoma in situ). CIN 3 is unlikely to regress spontaneously; if untreated, it may, over months or years, penetrate the basement membrane, becoming invasive carcinoma. About 80 to 85% of all cervical cancers are squamous cell carcinoma; most of the rest are adenocarcinomas. Sarcomas and small cell neuroendocrine tumors are rare. Invasive cervical cancer usually spreads by direct extension into surrounding tissues or via the lymphatics to the pelvic and para-aortic lymph nodes. Hematogenous spread is possible but rare. Staging: Cancers are clinically staged based on biopsy, physical examination, and chest x-ray results (see Table 7: Gynecologic Tumors: Clinical Staging of Cervical Carcinoma* ). If the stage is > IB1, CT or MRI of the abdomen and pelvis is typically done to identify metastases, although results are not used for staging. If MRI and CT are not available, cystoscopy, sigmoidoscopy, and IV urography, when clinically indicated, may be used for staging.

Table 7

Clinical Staging of Cervical Carcinoma*

Stage Description

Carcinoma in situ (CIN 3), intraepithelial carcinoma

I IA

Carcinoma strictly confined to the cervix Preclinical carcinoma (diagnosed only by microscopy, with a depth of invasion < 5 mm from the surface)

IA1

Measured invasion of stroma 3 mm in depth and 7 mm in width

IA2

Measured invasion of stroma > 3 mm and 5 mm in depth and 7 mm in width

IB

Clinically visible lesions confined to the cervix or preclinical lesions larger than those in stage IA2

IB1 IB2 II

Clinically visible lesions 4 cm Clinically visible lesions > 4 cm Extension beyond the cervix but not to the pelvic wall; involvement of the vagina but excluding the lower third

IIA IIB III

No obvious parametrial involvement Obvious parametrial involvement Extension to the pelvic wall, with rectal examination detecting no cancer-free space between the tumor and pelvic wall; involvement of the lower third of the vagina; all cases with hydronephrosis or with a nonfunctioning kidney secondary to the carcinoma

IIIA

Extension to lower third of the vagina but not to the pelvic wall

IIIB

Extension to the pelvic wall, hydronephrosis, or a nonfunctioning kidney

IV

Extension beyond the true pelvis or clinical involvement of the bladder or

rectal mucosa (bullous edema does not signify stage IV) IVA IVB Spread to adjacent pelvic organs Spread to distant organs

*Table is based on staging established by the International Federation of Gynecology and Obstetrics (FIGO) and American Joint Committee on Cancer (AJCC), 1995, 1996, 1997.

Depth of invasion should be measured from the base of the epithelium (surface or glandular) from which it originates. Vascular space involvement (venous or lymphatic) should not alter staging.

The purpose of this staging system is to establish a large database for study; thus, the system uses worldwide uniform diagnostic criteria. The system excludes results of tests that are less likely to be available worldwide (eg, MRI) because most cases of cervical cancer occur in developing countries. Because such tests are not used, findings such as parametrial invasion and lymph node metastases are often missed, and thus understaging is possible. When imaging tests suggest that pelvic or para-aortic lymph nodes are grossly enlarged (> 2 cm), surgical exploration, typically with a retroperitoneal approach, is occasionally indicated. Its sole purpose is to remove enlarged lymph nodes so that radiation therapy can be more precisely targeted and more effective.
Last full review/revision November 2008 by David M. Gershenson, MD; Pedro T. Ramirez, MD. Reference: www.merckmanuals.com

Murphy's kidney punch

Murphy's test A clinical test in which the examiner makes jabbing thrusts under the Pt's 12 rib, evoking pain and/or tenderness in Pts with renal inflammation or infection
McGraw-Hill Concise Dictionary of Modern Medicine. 2002 by The McGraw-Hill Companies, Inc.

th

Kidney punch or CVA Tenderness is elicited when gently tapping the area of the back overlying the kidney producing pain in people with an infection around the kidney (perinephric abscess) orpyelonephritis or renal stone. Since the kidney lies directly below this area, known as thecostovertebral angle, tapping disturbs the inflamed tissue causing pain. This medical test was first described by the American surgeon John Benjamin Murphy.

Post coital bleeding can happen when you are pregnant and when you are not pregnant. Below are the top reasons for bleeding after sex:

Infection of the cervix (cervicitis) Infection of the vagina (vaginitis) Abnormal cervical cells Fibroids Trauma of the vagina Trauma of the cervix Cervical polyp Uterine polyp Threatened miscarriage (if you are pregnant) Ectopic pregnancy (if you are pregnant) Pain in other regions of hypogastrium Pain localized in other areas of the lower part of abdomen, caused by the disease process within organs in this anatomical region. It may have diverse character and intensification. What organs are found in the Hypogastrium region? Bladder, Prostate(male), Ovaries(female),cervix(female), Testes(male), Penis(Male),Colon, and the Anus. Flank pain: A feeling of distress and agony caused by the stimulation of pain nerve endings in the flank. The clinician must consider urinary tract disorders, vascular disease, gastrointestinal processes, obstetric or gynecologic conditions, pulmonary illnesses, musculoskeletal problems, dermatologic entities, and neurologic

Erythematous Lesion: Redness of the cervix uteri surface caused by dilatation and congestion of the capillaries 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 Bone fractures Cervical cancers start as an abnormality of cells on the surface of the cervix. These abnormalities are not cancerous. They include dysplasia, squamous intraepithelial lesions (SIL) and carcinoma in situ. If undetected or untreated, these preinvasive abnormalities eventually may invade normal cells of the cervix. As a result, cancer may develop, invading surrounding tissues or lymph nodes. Reference: www.scribd.com. 2011

Staging
Cervical cancer is staged by the International Federation of Gynecology and Obstetrics (FIGO) staging system, which is based on clinical examination, rather than surgical findings. It allows only the following diagnostic tests to be used in determining the stage: palpation, inspection, colposcopy, endocervical curettage, hysteroscopy, cystoscopy, proctoscopy, intravenous urography, and Xray examination of the lungs and skeleton, and cervical conization. Stage I The carcinoma is strictly confined to the cervix (extension to the corpus would

be disregarded) IA Invasive carcinoma which can be diagnosed only by microscopy, with deepest invasion <5 mm and the largest extension >7 mm IA1 Measured stromal invasion of <3.0 mm in depth and extension of <7.0 mm IA2 Measured stromal invasion of >3.0 mm and not >5.0 mm with an extension of not >7.0 mm IB Clinically visible lesions limited to the cervix uteri or pre-clinical cancers greater than stage IA IB1 Clinically visible lesion <4.0 cm in greatest dimension

IB2 Clinically visible lesion >4.0 cm in greatest dimension Stage II Cervical carcinoma invades beyond the uterus, but not to the pelvic wall or to the lower third of the vagina

IIA Without parametrial invasion IIA1 Clinically visible lesion <4.0 cm in greatest dimension IIA2 Clinically visible lesion >4.0 cm in greatest dimension IIB With obvious parametrial invasion Stage III The tumour extends to the pelvic wall and/or involves lower third of the vagina and/or causes hydronephrosis or non-functioning kidney

IIIA Tumour involves lower third of the vagina, with no extension to the pelvic wall IIIB Extension to the pelvic wall and/or hydronephrosis or non-functioning kidney Stage IV The carcinoma has extended beyond the true pelvis or has involved (biopsy proven) the mucosa of the bladder or rectum. A bullous oedema, as such, does not permit a case to be allotted to Stage IV

IVA Spread of the growth to adjacent organs IVB Spread to distant organs Stage 1-A1 young women - conization wis clear margin. Parous women - hysterectomy. Stage 1-A2 laproscopic lymphadenectomy + vaginal trechelectomy + post operative radiotherapy. Stage 1B & 2A 1. Wertheim's hysterectomy . 2schauta vaginal hysterectomy + laparoscopic lymphadenectomy 3: primary radiotherapy 4: combined surgery & radiotherapy. Stage 2B, 3, 4 - chemotherapy

www.wikipedia.com

ow is cervical cancer staged?

The process of finding out how far the cancer has spread is called staging. Information from exams and diagnostic tests is used to determine the size of the tumor, how deeply the tumor has invaded tissues within and around the

cervix, and the spread to lymph nodes or distant organs (metastasis). This is an important process because the stage of the cancer is the key factor in selecting the right treatment plan. The stage of a cancer does not change over time, even if the cancer progresses. A cancer that comes back or spreads is still referred to by the stage it was given when it was first found and diagnosed, only information about the current extent of the cancer is added. A person keeps the same diagnosis stage, but more information is added to the diagnosis to explain the current disease status A staging system is a way for members of the cancer care team to summarize the extent of a cancer's spread. The 2 systems used for staging most types of cervical cancer, the FIGO (International Federation of Gynecology and Obstetrics) system and the AJCC (American Joint Committee on Cancer) TNM staging system, are very similar. Both systems classify cervical cancer on the basis of 3 factors: the extent of the tumor (T), whether the cancer has spread to lymph nodes (N) and whether it has spread to distant sites (M). The system described below is the most recent AJCC system, which went into effect January 2010. Any differences between the AJCC system and the FIGO system are explained in the text. This system classifies the disease in stages 0 through IV. Staging is based on clinical rather than surgical findings. This means that the extent of disease is evaluated by the doctor's physical examination and a few other tests that are done in some cases, such as cystoscopy and proctoscopy -- it is not based on the findings at surgery. If surgery is done, it may show that the cancer has spread more than the doctors first thought. This new information may change the treatment plan, but it does not change the patient's stage.

Tumor extent (T)

Tis: The cancer cells are only found on the surface of the cervix (in the layer of cells lining the cervix), without growing into deeper tissues. (Tis is not included in the FIGO system) T1: The cancer cells have grown from the surface layer of the cervix into deeper tissues of the cervix. The cancer may also be growing into the body of the uterus, but it has not grown outside of the uterus. T1a: There is a very small amount of cancer, and it can be seen only under a microscope. T1a1: The area of cancer is less than 3 mm (about 1/8-inch) deep and less than 7 mm (about 1/4-inch) wide. T1a2: The area of cancer invasion is between 3 mm and 5 mm (about 1/5-inch) deep and less than 7 mm (about 1/4-inch) wide. T1b: This stage includes stage I cancers that can be seen without a microscope. This stage also includes cancers that can only be seen with a microscope if they have spread deeper than 5 mm (about 1/5 inch) into connective tissue of the cervix or are wider than 7 mm. T1b1: The cancer can be seen but it is not larger than 4 cm (about 1 3/5 inches). T1b2: The cancer can be seen and is larger than 4 cm. T2: In this stage, the cancer has grown beyond the cervix and uterus, but hasn't spread to the walls of the pelvis or the lower part of the vagina. The cancer may have grown into the upper part of the vagina. T2a: The cancer has not spread into the tissues next to the cervix (called the parametria). T2a1: The cancer can be seen but it is not larger than 4 cm (about 1 3/5 inches). T2a2: The cancer can be seen and is larger than 4 cm. T2b: The cancer has spread into the tissues next to the cervix (the parametria) T3: The cancer has spread to the lower part of the vagina or the walls of the pelvis. The cancer may be blocking the ureters (tubes that carry urine from the kidneys to the bladder). T3a: The cancer has spread to the lower third of the vagina but not to the walls of the pelvis. T3b: The cancer has grown into the walls of the pelvis and/or is blocking one or both ureters (this is called hydronephrosis). T4: The cancer has spread to the bladder or rectum or it is growing out of the pelvis

Lymph node spread (N)

NX: The nearby lymph nodes cannot be assessed N0: No spread to nearby lymph nodes N1: The cancer has spread to nearby lymph nodes

Distant spread (M)

M0: The cancer has not spread to distant lymph nodes, organs, or tissues M1: The cancer has spread to distant organs (such as the lungs or liver), to lymph nodes in the chest or neck, and/or to the peritoneum (the tissue coating the inside of the abdomen).

Stage grouping
Information about the tumor, lymph nodes, and any cancer spread is then combined to assign the stage of disease. This process is called stage grouping. The stages are described using the number 0 and Roman numerals from I to IV. Some stages are divided into sub-stages indicated by letters and numbers. Stage 0 (Tis, N0, M0): The cancer cells are only in the cells on the surface of the cervix (the layer of cells lining the cervix), without growing into (invading) deeper tissues of the cervix. This stage is also called carcinoma in situ (CIS) or cervical intraepithelial neoplasia (CIN) grade III (CIN III). This stage is not included in the FIGO system. Stage I (T1, N0, M0): In this stage the cancer has grown into (invaded) the cervix, but it is not growing outside the uterus. The cancer has not spread to nearby lymph nodes (N0) or distant sites (M0). Stage IA (T1a, N0, M0): This is the earliest form of stage I. There is a very small amount of cancer, and it can be seen only under a microscope. The cancer has not spread to nearby lymph nodes (N0) or distant sites (M0). Stage IA1 (T1a1, N0, M0): The cancer is less than 3 mm (about 1/8-inch) deep and less than 7 mm (about 1/4inch) wide. The cancer has not spread to nearby lymph nodes (N0) or distant sites (M0). Stage IA2 (T1a2, N0, M0): The cancer is between 3 mm and 5 mm (about 1/5-inch) deep and less than 7 mm (about 1/4-inch) wide. The cancer has not spread to nearby lymph nodes (N0) or distant sites (M0). Stage IB (T1b, N0, M0): This stage includes stage I cancers that can be seen without a microscope as well as cancers that can only be seen with a microscope if they have spread deeper than 5 mm (about 1/5 inch) into connective tissue of the cervix or are wider than 7 mm. These cancers have not spread to nearby lymph nodes (N0) or distant sites (M0). Stage IB1 (T1b1, N0, M0): The cancer can be seen but it is not larger than 4 cm (about 1 3/5 inches). It has not spread to nearby lymph nodes (N0) or distant sites (M0). Stage IB2 (T1b2, N0, M0): The cancer can be seen and is larger than 4 cm. It has not spread to nearby lymph nodes (N0) or distant sites (M0). Stage II (T2, N0, M0): In this stage, the cancer has grown beyond the cervix and uterus, but hasn't spread to the walls of the pelvis or the lower part of the vagina. Stage IIA (T2a, N0, M0): The cancer has not spread into the tissues next to the cervix (called the parametria). The cancer may have grown into the upper part of the vagina. It has not spread to nearby lymph nodes (N0) or distant sites (M0). Stage IIA1 (T2a1, N0, M0): The cancer can be seen but it is not larger than 4 cm (about 1 3/5 inches). It has not spread to nearby lymph nodes (N0) or distant sites (M0). Stage IIA2 (T2a2, N0, M0): The cancer can be seen and is larger than 4 cm. It has not spread to nearby lymph nodes (N0) or distant sites (M0). Stage IIB (T2b, N0, M0): The cancer has spread into the tissues next to the cervix (the parametria). It has not spread to nearby lymph nodes (N0) or distant sites (M0). Stage III (T3, N0, M0): The cancer has spread to the lower part of the vagina or the walls of the pelvis. The cancer may be blocking the ureters (tubes that carry urine from the kidneys to the bladder). It has not spread to nearby lymph nodes (N0) or distant sites (M0). Stage IIIA (T3a, N0, M0): The cancer has spread to the lower third of the vagina but not to the walls of the pelvis. It has not spread to nearby lymph nodes (N0) or distant sites (M0). Stage IIIB (T3b, N0, M0; OR T1-3, N1, M0): either: The cancer has grown into the walls of the pelvis and/or has blocked one or both ureters (a condition calledhydronephrosis), but has not spread to lymph nodes or distant sites. OR

The cancer has spread to lymph nodes in the pelvis (N1) but not to distant sites (M0). The tumor can be any size and may have spread to the lower part of the vagina or walls of the pelvis (T1-T3). Stage IV: This is the most advanced stage of cervical cancer. The cancer has spread to nearby organs or other parts of the body.

Stage IVA (T4, N0, M0): The cancer has spread to the bladder or rectum, which are organs close to the cervix (T4). It has not spread to nearby lymph nodes (N0) or distant sites (M0). Stage IVB (any T, any N, M1): The cancer has spread to distant organs beyond the pelvic area, such as the lungs or liver. Last Medical Review: 12/16/2010 Last Revised: 10/26/2011 Reference: www.cancer.org

Rupture