Cervical Cancer

1. Cervical Cancer
RAHIL DALAL

2. Introduction

3.  Cervical cancer is a cancer arising from a premalignant lesion in the cervix
 It is a Squamous cell carcinoma (~ 90 %cases) type of solid tumor
 Cervical cancer is the third most common malignancy in women worldwide, and it
remains a leading cause of cancer-related death for women in developing
countries.

4. Etiology

5. With rare exceptions, cervical cancer results from genital infection with Human Papilloma Virus (HPV)
(mainly types 16 and 18), which is a known human carcinogen. Although HPV infections can be
transmitted via nonsexual routes, the majority result from sexual contact.
Consequently, major risk factors identified in epidemiologic studies are as follows:
 Early onset of intercourse
 Multiple sexual partners
 History of sexually transmitted diseases
 Multiparity (birth of >1 child at a time)
 smoking
 immunocompromised state (e.g., human immunodeficiency virus, transplant recipient)
 lower socioeconomic status
 poor diet (e.g., vitamin deficiency)
 alcoholism

7. Pathophysiology

8. The HPV infects the epithelium of the lower anogenital tract, including the cervical squamocolumnar
junction. This is a site of continuous metaplastic change.
The precursor lesion is called dysplasia or cervical intraepithelial neoplasia (CIN), which precedes the
development of invasive cervical cancer. CIN is characterized by cellular immaturity and disorganization
and increased mitotic change. Progression from CIN to invasive disease can be quite long with 66% of all
patients developing invasive carcinoma within 10 years.
The tumor becomes invasive when it breaks through the basement membrane into the underlying tissue.
The disease can spread by direct extension into the vagina or endometrium, then to the walls of the
pelvis, the bladder, and the rectum.
In addition to local invasion, tumor spread can occur through the rich lymphatic network of the cervix,
which anastomoses with those of the lower uterus. It spreads initially to lymph nodes in the pelvis, then to
the paraaortic lymph nodes, and distant sites. The most common sites of distant spread are the lung,
extrapelvic nodes, liver, and bone

12. Screening and
Prevention

13. Mass population screening with pap smears is effective at reducing the mortality from cervical
cancer worldwide.
The American Cancer Society provides Guidelines for cervical cancer screening and frequency of
Papanicolaou (PAP) tests
Vaccination against pathologic HPV appears to be an effective cervix cancer prevention strategy.
Vaccines are made with inactivated virus-like particles that are non-infectious but highly
immunogenic quadrivalent vaccine (having HPV types 16, 18, 6 and 11) has been approved for
use by the FDA for patients 9–26 years old and must be administered before HPV exposure to be
effective.

15. Signs and Symptoms

16. Preinvasive disease – completely asymptomatic and the disease is only detected with routine screening
by a PAP test.
Early invasive disease –
 abnormal vaginal bleeding (e.g., postcoital bleeding, intermenstrual bleeding)
 the vaginal discharge becomes more pronounced and can be a serosanguinous or yellowish vaginal
discharge that is frequently foul-smelling.
Advanced disease
 Anemia
 weight loss
 Fatigue
 lumbosacral or gluteal pain
 lower extremity swelling
 urinary or rectal symptoms, including uremia progressing to coma.

17. Diagnosis and Staging

18. If abnormal findings are discovered on the PAP smear, a procedure known as colposcopy should be
performed to identify abnormal areas that warrant biopsy and to determine the extent of the lesion. The
colposcope is a low-power magnification device that allows visualization of mucosal abnormalities. All
visible or suspicious lesions should be biopsied deeply enough to assess for invasion.
Patients with a biopsy positive for invasive cervical cancer should undergo one or more of the following
tests to complete a clinical staging workup:
1. a careful physical examination, including bimanual and rectovaginal examinations
2. CBC
3. SMA-12 (Sequential Multiple Analysis-12)
4. chest x-ray
5. an intravenous pyelogram
6. Cystoscopy or proctoscopy

20. Treatment

22. The goal of primary treatment is to cure the patient. This is an achievable goal for early stage
disease. It is also possible to cure patients that present with advanced stage disease, although it is
less likely.
Treatment is based on the clinical stage and individual patient characteristics.
In general, the treatment of early stage disease (stage I and stage IIA) focuses on surgery or
radiation.
Primary treatment may include surgery and radiation if the surgical findings leave the patient at
high risk of developing recurrent disease
For patients with advanced stage disease (bulky stages IIB, III, and IVA), surgery no longer plays a
primary role in the primary treatment. Instead, primary treatment is focused on radiation.

23. CHEMOTHERAPY
Chemosensitization. Chemosensitization refers to the use of chemotherapy just prior to
radiation to sensitize the patient to the effects of radiation. In the treatment of cervical cancer,
the use of cisplatin-containing chemotherapy concurrent with radiation improves response rates
and survival.
Proposed mechanisms whereby cisplatin increases the effectiveness of radiation include
1. a complementary action by working on different phases of the cell cycle
2. direct cell cytotoxicity
3. tumor cell synchronization
4. inhibition of sublethal radiation repair.

24. CHEMOTHERAPY
Chemotherapy for Recurrent Disease. Recurrent disease is defined as reappearance of tumor
more than 6 months after treatment. At this point, curative therapy is unlikely. Treatment should
be focused on palliation of symptoms and pain management.
Drugs include Paclitaxel, Cisplatin, Carboplatin, Vinorelbine, Topotecan, Docetaxel

25. RADIATION
Radiation therapy is appropriate in the management of all stages of cervical cancer
Types of radiation include
1. whole pelvic radiotherapy (WPRT)
2. Intra-cavitary radiotherapy (ICRT)
3. high-dose rate radiotherapy (HDRT).

26. SURGERY
Surgery is the therapy of choice in early invasive cervical cancer
1. RAH – radical abdominal hysterectomy (removal of uterus)
2. BSO – bilateral salpingo–oophorectomy (removal of ovaries + fallopian tubes)
3. BLPLND – bilateral pelvic lymph node dissection
4. Pelvic exenteration – a complete surgical removal of all pelvic organs (uterus, fallopian tubes, ovaries, cervix,
vagina, bladder, and rectum) is followed by reconstruction [FOR VERY SELECTED CLASS OF PATIENTS AND IN
RECURRENT DISEASE ONLY]

27. References
E T Herfindal et. al. ; “Textbook of Therapeutics: Drug and Disease Management”, 8th Ed., Pg.
2529 – 2534
Fauci et. al. ; “Harrison’s Principles of Internal Medicine”, 18th Ed.
emedicine.medscape.com