Cervical Cancer

Incidence

There are approximately 15,000 new cases of cervical cancer reported annually and 4,000-5,000 associated deaths.

Risk Factors

Significant risk factors for cervical cancer include early age at first intercourse, multiple sexual partners, multiparity, infection with Human Papilloma Virus (HPV) (Specifically Types 16 and 18), non-barrier methods of birth control, sexual contact with high risk males and smoking.

Pathology

Squamous carcinomas comprise the majority of cases (85%) followed by adenocarcinomas (10-15%), which include the less common adenosquamous carcinoma, and the remainder of cases comprised of the rarer tumors which includes small cell, sarcomas, lymphomas, and melanomas.

Routes of Spread

Cervical carcinoma spreads by one of three major routes:
1. Direct invasion into surrounding structures which include the parametria, corpus, and vagina.
2. Lymphatic dissemination
3. Hematogenous dissemination
4. Intraperitoneal implantation

Clinical Features

The two predominant symptoms of cervical cancer are discharge and abnormal vaginal bleeding. Other complaints include urinary frequency and pain. The physical exam may vary depending on the site of the lesion (endocervix or exocervix). A careful visual inspection as well as  both bimanual and rectovaginal palpation are necessary to identify the size and extent of the lesion.

Pretreatment Work-Up

All cases of cervical cancer should have as part of the pre-treatment work-up the following components:
1. Careful physical exam including biopsy of the lesion
2. Chest X-ray
3. Routine lab tests

Other procedures may be employed in more advanced disease or in the presence of symptoms (cystoscopy, proctoscopy, BE, CT scan, etc). 

Note: The allowed procedures to assign a patient to a FIGO stage are limited to physical exam, conization, IVP, BE, cystoscopy, proctoscopy, and CXR.

Staging

Stage I: Those lesions confined to the cervix (uterine involvement is disregarded).

Ia- Preclinical cervical cancers diagnosed by microscopy alone.
Ia1-Measured invasion of stroma no greater than 3 mm in depth and no wider than 7 mm.
Ia2- Measured invasion of stroma greater than 3 mm and no greater than 5 mm in depth and no wider than7 mm.

IB- Lesions of greater dimension than Stage Ia whether seen clinically or not.
Ib1- Clinical lesions no greater than 4 cm in size.
Ib2- Clinical lesions greater than 4 cm in size.

Stage II: The carcinoma extends beyond the cervix, but has not extended to the pelvic sidewall or the lower 1/3 of the vagina.

IIA- No obvious parametrial involvement.
IIB- Parametrial involvement.

Stage III: The carcinoma has extended to the pelvic wall with no cancer free space between the tumor and the pelvic wall. The tumor involves the lower 1/3 of the vagina.All cases of hydronephrosis or non-functioning kidney unless secondary to unrelated cause.

IIIB- No extension to the pelvic sidewall, but involvement of the lower 1/3 of the vagina.
IIIB- Extension on the pelvic wall or hydronephrosis or nonfunctioning kidney.

Stage IV: The carcinoma has extended beyond the true pelvis or has clinically involved the mucosa of the bladder or rectum.

IVA- Spread of growth to adjacent organs.
IVB- Spread of growth to distant organs.

Note: The term microinvasive cervical cancer is sometimes applied to Stage Ia lesions. Unfortunately there are two separate definitions that are used which are important when considering therapy options. This diagnosis must be made from either a cone or hysterectomy specimen.

1. International Federation of gynecology and Obstetrics (FIGO) Definition: See definition above under FIGO stage Ia.

2. Society of Gynecologic Oncologists (SGO) Definition: Microinvasion as defined by the SGO must satisfy a depth of invasion in one or more foci of 3 mm or less and have no lymphovascular involvement.

Treatment

Stage Ia- Lesions which satisfy the SGO definition of microinvasion may be treated conservatively with any of the following modalities:

1. Simple hysterectomy
2. Conization in cases where maintenance of fertility is at issue.
3. Intracavitary radiotherapy in patients who are not operative candidates.

Lesions that do not satisfy the SGO definition (LVSI or invasion >3 mm) are at significantly increased risk for recurrence when treated conservatively therefore radical hysterectomy and lymph node dissection or radiotherapy should be employed.

Stages IB and IIA- Surgery or radiotherapy result in similar cure rates when patients are carefully selected. Squamous lesions less than 4-5 cm and adenocarcinomas less than 3 cm are potential surgical candidates. The standard treatment options are as follows:

1. Type III radical hysterectomy and pelvic lymph node dissection. In patients with risk factors on pathologic evaluation (e.g., lymph node metastases) are also given adjuvant radiotherapy.
2. Radiotherapy with 40-45 Gy external and two intracavitary applications.
3. Simple hysterectomy after pelvic radiotherapy; this primarily indicated in patients whose tumor responds slowly to radiotherapy or in whom vaginal anatomy precludes optimal intracavitary placement. 

Stages IIB through IVA- Radiotherapy is the treatment of choice for locally advanced disease. There are certain situations where surgery may be used as adjunctive therapy. In cases of Stage IVA without parametrial involvement and cases of persistent central disease following radiotherapy.

Stage IVB- Chemotherapy for disseminated disease is the primary treatment for Stage IVB. Radiotherapy can be used for local control and palliation of symptoms in this setting.

Recurrent Disease- Patients with central recurrence may be managed with an exenteration in the absence of contraindicating factors. Those patients with prior radiation and extensive pelvic recurrence or distant metastatic disease are treated in a similar fashion as those patients with Stage IVB.

Prognostic Factors

Stage I- Lymph vascular involvement, tumor size, depth of invasion, and presence of lymph node metastasis are important factors.

Stage II-IV- The major prognostic variables include stage, presence of lymph node metastasis, tumor volume, age, and performance status.

Survival

Stage I- Squamous 65-90%; Adenocarcinoma 70-75%
Stage II- Squamous 45-80%; Adenocarcinoma 30-40%
Stage III- Squamous up to 60%; Adenocarcinoma 20-30%
Stage IV- For both Squamous and Adenocarcinoma <15%

Recommended Follow-Up

Of those patients who do have recurrence of their disease; 50% are diagnosed in the first year, 75% are diagnosed by 2 years and 95% are diagnosed within 5 years. Follow-up surveillance is recommended as follows:

1. Physical exam every 3 months for the 2 years every 6 months during the fourth through fifth year and every 6 months thereafter.
2. PAP smear with each exam.
3. CXR annually.
4. Squamous Cell Antigen determination at each visit.