Cervical Cancer

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Definition/Description

Cervical cancer is a type of cancer that forms within the tissues of the cervix.[1]The cervix connects the uterus with the vagina (birth cancal).[1], [2]The endocervix is the portion of the cervix closest to the uterus whereas the exocervix or ectocervix is closest to the vagina.[2] The cervix is covered in two main types of cells: squamous cells found on the exocervix, and glandular cells on the endocervix.[2] Squamous and glandular cells come together at the area known as the transformation zone. It is here where most cervical cancers originate.[2] Gradually, the normal cells lining this area develop pre-cancerous changes that transform into cancer.[2] Cervical cancer typically grows at a slow rate and presents asymptomatically.[1] Therefore, it is recommended to receive routine Papanicolaou (Pap) smears to test for changes in the lining of the cervix and/or the development of cancerous cells.[1]                                                                                                                       
                                       Cervical-Cancer-Picture.jpg

Prevalence

In the United States, cervical cancer is the fourteenth most common type of cancer found in women, and the third most common gynecological malignancy.[3],[4] However worldwide, cervical cancer is the most commonly found type of cancer in women.[3] In the United States, diagnosis of invasive stage cervical cancer has declined (75% decline since the 1960s) steadily.[3][4]Screening for cervical cancer has become more common due to the introduction of the Pap smear in the 1930’s which made early detection possible.[5] Although cervical cancer is the most common cause of gynecological cancer-related death worldwide, mortality rates have decreased significantly in the United States (more than 45% since the early 1970s).[4],[5]


In the United States, approximately 11,000 women are diagnosed with cervical cancer and 3,700 women die due to the disease each year.[5] Worldwide,nearly 500,000 women are diagnosed with cervical cancer annually.[6] The disease accounts for 288,000 deaths per year.[5]

                                                                                                                                                                                                                                                          Fig1.jpg

                                    80% to 85% of cervical cancer related deaths occur in developing countries.[6]                    

                                                                                                         

Pre-invasive carcinoma in situ (no invasion of surrounding tissues) is more common in women 30-40 years of age.[4] Invasive carcinoma is more frequent in women over 40 years of age.[4] Women ages 65 and over account for 25% of new cases of cervical cancer.[5]
 

Characteristics/Clinical Presentation

  • May be asymptomatic (early stages)[4]
  • Painful intercourse or pain after intercourse[4]
  • Unexplained or unexpected bleeding (after intercourse or between menstrual periods)[3],[4]
  • Watery, foul-smelling vaginal discharge (serosanguineous or yellowish color)[3],[4]
  • Pelvic, epigastric, or low back pain (with large lesions)[3],[5]
  • Hemiparesis, headache (cancer recurrence with brain metastases)[4]
  • Bowel and bladder problems (later stages)[5]

Stages2.jpg


Clinical Staging for Cervical Cancer[5]

Cervical cancer is staged by the International Federation of Gynecology and Obstetrics (FIGO) staging system, based on clinical examination rather than surgical findings. For premalignant dysplastic changes, cervical intraepithelial neoplasia (CIN) grading is used.

*If the woman is treated surgically, the pathology report can be used to provide a separate pathologic stage; this does not replace the original clinical stage.

Stage

Characteristics
0

Full-thickness involvement of the epithelium (surface) without invasion into the stroma (support structure); carcinoma in situ (CIN grades 1, 2, or 3 are assigned)
I

Invaded the cervix but has not spread any further

IA
Small enough it can only be diagnosed by microscopy; there are no visible lesions


IA1 Area of invasion is less than 3 millimeters (1/8-inch) deep and less than 7 millimeters (1/4-inch) wide


IA2 Area of invasion is between 3 and 5 millimeters (about 1/5-inch) with horizontal spread of 7 millimeters or less

IB
Visible lesion or a microscopic lesion with more than 5 millimeters of depth or horizontal spread of more than 7 millimeters; has spread into connective tissue of the cervix


IB1 Visible lesion 4 centimeters or less in greatest dimension


IB2 Visible lesion more than 4 centimeters
II

Invades beyond cervix to upper 1/3 of the vagina only

IIA
Without parametrial (tissue next to the cervix) invasion

IIB
With parametrial invasion
III

Extends to pelvic wall or lower 1/3 of the vagina

IIIA
Involves lower 1/3 of vagina but not the pelvic wall

IIIB
Extends to pelvic wall and/or blocks urine flow to the bladder; may have spread to pelvic lymph nodes
IV

Extends beyond the true pelvis

IVA
Invades mucosa of bladder or rectum and/or extends beyond true pelvis

IVB
Distant metastasis to other organ (beyond the pelvis) such as lungs

Associated Co-morbidities

Cervical cancer is associated with and may be the manifestation of human papillomavirus (HPV).[5]

Medications

Drugs Approved to Prevent Cervical Cancer[1]

  • Cervarix (Recombinant HPV Bivalent Vaccine)
  • Gardasil (Recombinant HPV Quadrivalent Vaccine)

      -Gardasil protects against two strains of HPV that cause cervical cancer.[5] The vaccine is administered to females between the ages of 9 and 26.[5] The vaccination is especially important for women who do not have access to regular cervical cancer screenings.[5]

Drugs Approved to Treat Cervical Cancer[1],[7]

*Systemic chemotherapy involves injecting or orally administering cancer-treating drugs.[7] These drugs then enter the bloodstream, and travel throughout the body, reaching areas of cancerous growth.[7]Chemotherapy can work in the following ways:[1][8]


                                                           -Cure the cancer
                                                           -Shrink the cancer
                                                           -Relieve symptoms
                                                           -Prolong life span by controlling cancer or putting it into remission


Chemotherapy is often delivered in cycles.[7] Periods of treatment are followed by periods of recovery.[7]

  • Blenoxane (Bleomycin)-mixture of cytotoxic glycopeptide antibiotics; Side effects- pulmonary fibrosis, hypotension, mental confusion, fever, chills and wheezing.[9]
  • Cisplatin*-sterile aqueous solution that contains sodium chloride in water for injection; Side effects- renal toxicity, nausea and vomitting, myelo-suppression, ototoxicity, facial edema, bronchoconstriction, tachycardia, hypotension[9]
  • Hycamtin (Topotecan Hydrochloride)- antitumor drug with topoisomerase 1-inhibitory activity[9]
  • Platinol (Cisplatin)
  • Platinol-AQ (Cisplatin)
  • Topotecan Hydrochloride (Hycamtin)
  • Carboplatin
  • Paclitaxel* (Taxol)- nonaqueous solution with antitumor activity; Side effects- anaphylaxis, dyspnea, hypotension, angioedema, urticaria (hives)[9]
  • Gemcitabine (Gemzar)-nucleoside metabolic inhibitor that exhibits antitumor activity; Side effects- pallor, easy bruising or bleeding, unusual weakness, decreased urination, nausea, upper stomach pain, dark urine, clay-colored stools, jaundice, chest pain, pain spreading to arm or shoulder, diaphoresis, signs of allergic reaction[9]

 *Currently, Cisplatin is the most effective single chemotherapy drug for recurrent disease.[10] When administered with paclitaxel, the combination is more effective than cisplatin alone (in terms of response rate and survival).[10]

Drug Combinations Used in Cervical Cancer[1]

  • Gemcitabine-Cisplatin

Diagnostic Tests/Lab Tests/Lab Values

Medical professionals who are able to diagnose cervical cancer include:[11]

  • Gynecologists
  • Obstetricians
  • Family physicians
  • Nurse practitioner
  • Physican assistants
  • Internists


Screening Tests:

  • Pap smear

      A Pap smear, also referred to as a Pap test, tests cervical cells for abnormal changes.[12] It is these abnormal cellular changes that can lead to cervical cancer if left untreated.[12] Cervical cancer is highly preventable, given that regular Pap smears are performed.[12] It is recommended that women receive annual Pap smears beginning three years after the onset of vaginal intercourse but no later than 21 years of age.[5] Women aged 70 and older, with an intact cervix, are no longer required to recevie Pap smears if they have had no positive test results within the last 10 years.[5] Women who do not have a cervix (ex. hysterectomy), as well as no history of abnormal Pap results or cervical cancer can discontinue annual Pap smears.[12] However, some medical professionals support routine Pap smears regardless of age, presence of cervix, or past negative test results.[5] Even if not currently sexually active, or protected sex is being practiced, regular Pap smears should still be performed.[12]

                                               Pap-smear-1.jpg


Diagnostic Tests:

-Imaging:[13]

*Tumor must be at least stage 1b or greater to be seen on a radiograph.

  • Magnetic resonance imaging (MRI)- imaging modality of choice for depicting primary tumor
  • Ultrasound- tumor appears as a hypoechoic (dark) cervical mass; should not be used as primary diagnostic tool
  • Computed tomography (CT)-used to assess disease in more advanced stages and/or monitor distant metastasis
  • Positron emission tomography (PET)-CT- imaging modality of choice for staging cervical cancer


-Biopsy:[2]

  • Colposcopic
  • Endocervical curetttage (scraping)
  • Cone

Etiology/Causes

The presence of HPV is a common feature in the majority of individuals diagnosed with cervical cancer.[5] Clinical studies show that the transference of HPV during unprotected sexual intercourse is the primary cause of cerviclal cancer.[5] The disease can spread through local extension and through the lymphatic system to the retroperitoneal lymph nodes.[4]

                                        Avoid cancer.jpg


Risk Factors:[4],[5]

  • Early age at first sexual intercourse (17 years or younger)
  • Early age at first pregnancy
  • Tobacco use, including exposure to passive smoke
  • Low socioeconomic status (lack of screening)
  • History of any sexually transmitted disease (STD), especially HPV and human immunodeficiency virus (HIV)
  • History of multiple sex partners (five or more)
  • History of childhood sexual abuse
  • Intimate partner abuse
  • Women whose mothers used the drug diethylstilbestrol (DES) during pregnancy
  • Hormonal contraceptive use
  • Ethnic background- African-American women experience a 72% higher incidence compared with Caucasian women
  • High parity (number of births)
  • Alcohol and drug use (impaired decision making)

Systemic Involvement

Cervical cancer affects the female reproductive system.

Pressure from tumor on neighboring structures can affect the urinary system and gastrointestinal system (bowel).[5]

Metastasis has been known to occur to the central nervous system (CNS), pulmonary system, urinary system (bladder), gastrointestinal system (rectum), retroperitoneal lymph nodes, paracervical lymphatics and parametrial lymphatics.[4]

Medical Management (current best evidence)

The treatment of cervical cancer varies depending on clinical staging.

Recommended Treatment Based on Clincal Staging for Cancer of the Cervix[3]

Stage
Treatment
0
Cryosurgery, laser surgery, loop electrosurgical excision procedure (LEEP), electrocautery
I
LEEP, laser surgery, conization, cryosurgery, radiation without surgery, total hyterectomy with or without bilateral pelvic lymphadenectomy
II
Radiation, radical hysterectomy and pelvic lymphadenectomy often followed by radiation
III
Radiation with external beam or implant(s) with or without hydroxyurea
IV
Radiation with external beam or implant(s) with or without hydroxyurea, chemotherapy (cisplatin or ifosfamide with distant site involvement)

Recent findings have shown that women staged with CIN 2 or 3 may not require immediate treatment, as the abnormality may regress naturally.[5]

Previous research has shown that cisplatin-based chemotherapy combined with radiation have increased survival rates in women with locally advanced cervical cancer.[5]

Recently, new research has been conducted to determine the effectiveness of concurrent cisplatin-based chemotherapy with an epidermal growth factor receptor inhibitor (E).[14] Epidermal growth factor receptor (EGFR) is commonly overexpressed in cervical cancer; therefore, the inhibitor, which has antitumor effects, acts to decrease the expression of EGFR.[14] The results of this study suggest that treatment with E combined with cisplatin-based chemotherapy has been shown to work against a locally advanced cervical cancer.[14]

Physical Therapy Management (current best evidence)

The primary role of physical therapy associated with cervical cancer is education. Physical therapists (PT's) should be an advocate to their patients to stay regular with Pap smears and to practice other preventative measures (physical examinations, vaccines, protected sex). It is important for PT's to gather a thorough patient history, including questions that encompass issues such as vaginal bleeding, GI or genitourinary function, location of pain and discomfort, and pre-existing comorbidities.[5] If issues of concern are found during the evaluation, PT's should refer the patient to their primary care physician for further testing.

                                                Hope.jpg

PT's should look for signs and symptoms of metastasis in women with a previous history of cervical cancer. Lymph node palpation is an important component of the examination due to the high rate of metastasis to this location.[5] Questions that address possible warning signs of metastasis (ex. rapid weight loss, night pain/sweats, vaginal bleeding, fatigue, frequent infections) should be included in patient history.[4] If issues of concern are found during the evaluation, PT's should refer the patient to their primary care physician for further testing.

Women who have a current diagnosis of cervical cancer can benefit from physical therapy services. Physical therapy provides symptom relief by addressing impairments such as fatigue, muscle weakness and management of pain.[4]

While treating patients with cancer, it is important for PT's to review hematological values.[4] Aerobic exercise is contraindicated for patients receiving chemotherapy treatments when lab values are as follows:[4]

Platelet count <50,000/mm3
Hemoglobin <10g/dL
White blood cell count <3,000/mm3
Absolute granulocytes <2,500/mm3

In an outpatient setting, it is recommended for PT's to moniter vital signs and rate of percieved exertion (RPE) during exercise when working with patients with cancer.[4]


-Local vaginal treatment of the cervix:[15]

  • Escharotic treatment- This plant and mineral based extract is applied to the surface of the cervix. It contains proteolytic properties that dissolve the top layer of cervical cells, which are affected by the HPV virus.
  • Vaginal suppository treatment- Vag pak acts to enhance the immune system and rid cervical cells of infection.

Differential Diagnosis

Benign Conditions:[16][13]

  • Polyps
  • Cervical conditions (infections, polyps, myomas)
  • Iatrogenic (birth control pills, HRT, IUD)
  • Cervical ectopic pregnancy (consider with women of childbearing age)


Malignant Conditions:[16][13]

  • Endometrial cancer with cervical invasion
  • Other cervical malignant condition (sarcoma, lymphoma, metastasis)
  • Invasion of cervix from other organ in proximity:

                     -bladder cancer

                     -rectal cancer

                     -vaginal cancer

                     -uterine cancer

Case Reports/ Case Studies

Neoadjuvant chemotherapy followed by vaginal radical trachelectomy in bulky stage IB1 cervical cancer: Case report

Successful neoadjuvant chemotherapy for large cell neuroendocrine carcinoma of the cervix: A case report.

Port site metastasis after robotic-assisted laparoscopic hysterectomy for uterine cervical cancer: a case report and literature review.

Less radical surgery for patient with early-stage cervical cancer.

Resources

National Institue of Cancer, Cervical Cancer: http://www.cancer.gov/

American Cancer Society, Cervical Cancer: http://www.cancer.org/

NC Cervical Cancer Resource Directory: http://www.ccresourcedirectory.org/


Recent Related Research (from Pubmed)

see tutorial on Adding PubMed Feed

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References

see adding references tutorial.

  1. 1.0 1.1 1.2 1.3 1.4 1.5 1.6 1.7 Available at: http://www.cancer.gov/cancertopics/types/cervical. Accessed March 18, 2014.
  2. 2.0 2.1 2.2 2.3 2.4 2.5 Available at: http://www.cancer.org/cancer/cervicalcancer/detailedguide/cervical-cancer-what-is-cervical-cancer. Accessed March 18, 2014.
  3. 3.0 3.1 3.2 3.3 3.4 3.5 3.6 Ph.d. SE, Ph.d. KL. Understanding Pathophysiology. Mosby Incorporated; 2011.
  4. 4.00 4.01 4.02 4.03 4.04 4.05 4.06 4.07 4.08 4.09 4.10 4.11 4.12 4.13 4.14 4.15 4.16 4.17 Goodman CC, Snyder TE. Differential Diagnosis for Physical Therapists, Screening for Referral. W B Saunders Company; 2012.
  5. 5.00 5.01 5.02 5.03 5.04 5.05 5.06 5.07 5.08 5.09 5.10 5.11 5.12 5.13 5.14 5.15 5.16 5.17 5.18 5.19 5.20 5.21 5.22 Reviews CT. e-Study Guide for: Pathology: Implications for the Physical Therapist by Catherine C. Goodman, ISBN 9781416031185. Cram101 Textbook Reviews; 2012.
  6. 6.0 6.1 Available at: http://www.rho.org/about-cervical-cancer.htm. Accessed March 18, 2014.
  7. 7.0 7.1 7.2 7.3 7.4 Available at: http://www.cancer.org/treatment/treatmentsandsideeffects/treatmenttypes/chemotherapy/chemotherapyprinciplesanin-depthdiscussionofthetechniquesanditsroleintreatment/chemotherapy-principles-types-of-chemo-drugs. Accessed March 19, 2014.
  8. Available at: http://www.cancerresearchuk.org/cancer-help/about-cancer/treatment/chemotherapy/about/how-chemotherapy-works. Accessed March 18, 2014.
  9. 9.0 9.1 9.2 9.3 9.4 Available at: http://www.rxlist.com/script/main/hp.asp. Accessed March 19, 2014.
  10. 10.0 10.1 Cervical cancer. The Lancet. 2003;361(9376):2217.
  11. Available at: http://www.webmd.com/cancer/cervical-cancer/cervical-cancer-when-to-call-a-doctor. Accessed March 19, 2014.
  12. 12.0 12.1 12.2 12.3 12.4 Available at: http://www.womenshealth.gov/publications/our-publications/fact-sheet/pap-test.html. Accessed March 20, 2014.
  13. 13.0 13.1 13.2 Available at: http://radiopaedia.org/articles/carcinoma-of-the-cervix. Accessed March 19, 2014.
  14. 14.0 14.1 14.2 Nogueira-rodrigues A, Moralez G, Grazziotin R, et al. Phase 2 trial of erlotinib combined with cisplatin and radiotherapy in patients with locally advanced cervical cancer. Cancer. 2014;
  15. Cite error: Invalid <ref> tag; no text was provided for refs named Yellow
  16. 16.0 16.1 Available at: http://oncolex.org/en/Gynecological-cancer/Diagnoses/Cervical-cancer/Background/DifferentialDiagnoses. Accessed March 19, 2014.