Philippine Society of Oncologists, Inc.

Officers 2006
President		Divina B. Esteban, MD
Vice President		Alfredo Y. Pontejos, MD
Secretary		Luzviminda S. Kwong, MD
Treasurer		Enrico D. Tangco, MD
Immediate Past President		Rafael S. Claudio, MD
Executive Council
Members		Romulo S. de Villa, MD, PhD Nelia S. Tan-Liu, MD Juanita Lu-Lim, MD Teresita DV Tuazon, MD Gil M. Vicente, MD

Society of Gynecologic Oncologists of the Philippines

Officers 2005-2007
President		Efren J. Domingo, MD, PhD
Vice President		Rey H. De Los Reyes, MD, MHSA
Secretary		Ma. Cynthia F. Tan, MD
Treasurer		Maria Lilibeth L. Sia Su, MD
PRO		Gil S. Gonzalez, MD
Board of Directors		Teresita B. Cardenas, MD Elsie R. Dancel, MD Aris Luke I. Dungo, MD Cecilia L. Llave, MD, PhD Manuel S. Manabat, MD Jose B. Moran, MD Mary Christine F. Palma, MD Wilhelmina D. Rivera, MD
Executive Board Assistant		Jericho Thaddeus P. Luna, MD
Philippine Board of Gynecologic Oncology
Chairman		Genara M. Limson, MD
Members		Gil S. Gonzalez, MD
		Cecilia L. Llave, MD, PhD

The Clinical Practice Guidelines for Cervical Cancer

I. INCIDENCE:
• Age Standardized Rate – 20.0/100,000¹
• Age Incidence:

- PGH and Rizal province between 40 and 60 years old
- Same observation nationwide and worldwide
- Age specific incidence (Rizal province) between 30 and 35 years old

II. RISK FACTORS
• Multiple sexual partners
• Early sexual activity
• Multiparity
• History of sexually transmitted infection
• History of such infection in the sexual partner
• Smoking history - 40 pack years

Table I. Relative Risk* of Factors Associated with Cervical Cancer2
RISK FACTORS	Relative Risk
HIV	Very High
Moderate Dysplasia on Pap Smear within past 5 years	Very High
Intercourse within one year of menarche	16
No prior screening	10
HPV (depending on subtype)	2.5 - 3.0
Six or more lifetime sexual partners	5
Low socioeconomic class	5
Race (black vs. white)	2.5
Smoking	2
Oral contraceptive pill use	1.2 - 1.5
Barrier contraception	0.5

*DEFINITION: The Relative Risk Factor (RR) of a disease is the ratio of the incidence in people with the risk factor (exposed persons) to the incidence in people without the risk factor (unexposed persons)³. The farther the RR is from 1.0, the greater the difference in risk between the two groups⁴.

III. PRIMARY PREVENTION
• Monogamous sexual relationship between husband and wife
• Delay in onset of sexual intercourse
• NOTE: There is a greater than twofold risk of cervical cancer for those starting intercourse at ages 14-15 years versus those over 20 years⁵.
• Use of barrier contraceptives like condoms (for male and female) and diaphragms
• Prompt and adequate treatment of sexually transmitted infections
• HPV Vaccination - for females 9-26 years old, may be given.

IV. SECONDARY PREVENTION

A. RECOMMENDED SCREENING⁶
• When to start screening

Approximately 3 years after onset of sexual activity

• When to discontinue screening

Age >70 years with an intact cervix plus a history of a >3 consecutive normal smears & no history of abnormal cytology within the 10-year period prior to 70

Note:
For high risk patients (>1 risk factor), annual Pap smear is still recommended even if the ACS guidelines for discontinuation of screening is satisfied.

• Screening after hysterectomy

Not indicated following hysterectomy for benign disease

Note:
1. CIN 2/3 are exceptions to these benign conditions and warrant screening even after hysterectomy
2. For post-hysterectomy (for benign disease) high risk patients, annual Pap smear is still recommended to screen for vaginal intra-epithelial neoplasia (VAIN)

• Screening interval
Annual with conventional cytology OR Every 2 years with liquid-based cytology
THEN
At or after age 30, after 3 consecutive normal smears, may decrease screening interval every 2-3 years

Note:
1. For high risk patients (>1 risk factor), annual Pap smear is recommended.
2. For centers without a cytology unit, annual direct visual inspection (DVI) is recommended.

B. CERVICAL CANCER SCREENING USING PAPANICOLAOU SMEAR & DIRECT VISUAL INSPECTION

• Please refer to Figure 1.

V. CLINICAL PRESENTATION

A. Early symptoms:
1. Vaginal bleeding - most important symptom

a. induced by sexual intercourse or internal examination
b. intermenstrual

2. Vaginal discharge

B. Late symptoms:
1. bone pain
2. urinary and bowel disturbances
3. leg edema

VI. DIAGNOSIS

A. Minimal requirements for diagnosis

1. cervical punch biopsy for those with grossly evident tumor
2. colposcopy and colpo-guided biopsies following investigation of an abnormal Pap smear
3. pelvic examination including rectovaginal examination

B. Optional examinations (but are included in the clinical staging as recommended by FIGO)

1. Blood examinations including CBC, Liver function tests, renal function tests
2. Chest x-ray
3. KUB-IVP
4. Cystoscopy/ proctosigmoidoscopy

VII. MANAGEMENT OF ABNORMAL PAP SMEAR

• Please refer to Figure 2.

VIII. MANAGEMENT OF PRE-MALIGNANT LESIONS

• Please refer to Figure 3.

IX. FIGO CLINICAL STAGING FOR CERVICAL CANCER (Figure 4)

Stage I	Carcinoma strictly confined to the cervix; extension to the uterine corpus should be disregarded.
Stage IA	Invasive cancer identified only microscopically. All gross lesions even with superficial invasion are stage Ib cancers. Invasion is limited to measured stromal invasion with a maximum depth of 5 mm* and no wider than 7 mm.
Stage IA1	Measured invasion of the stroma no greater than 3 mm in depth and no wider than 7 mm in diameter
Stage IA2	Measured invasion of stroma greater than 3 mm but no greater than 5 mm in depth and no wider than 7 mm in diameter
Stage IB	Clinical lesions confined to the cervix or preclinical lesions greater than Stage IA
Stage IB1	Clinical lesions no greater than 4 cm in size.
Stage IB2	Clinical lesions greater than 4 cm in size
Stage II	Carcinoma that extends beyond the cervix but has not extended onto the pelvic wall. The carcinoma involves the vagina but not as far as the lower third
Stage IIA	No obvious parametrial involvement. Involvement of up to the upper two thirds of the vagina.
Stage IIB	Obvious parametrial involvement, but not onto the pelvic sidewall.
Stage III	Carcinoma that has extended onto the pelvic sidewall. On rectal examination, there is no cancer free space between the tumor and the pelvic sidewall. The tumor involves the lower 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.
Stage IIIA	No extension onto the pelvic sidewall but involvement of the lower third of the vagina
Stage IIIB	Extension onto the pelvic sidewall or with hydronephrosis or nonfunctioning kidney
Stage IV	Carcinoma that has extended beyond the true pelvis or has clinically involved the mucosa of the bladder / or rectum
Stage IVA	Spread of the tumor onto adjacent pelvic organs
Stage IVB	Spread to distant organs

* The depth of invasion should not be more than 5 mm taken from the base of the epithelium, either surface or glandular, from which it originates. Vascular space involvement, either venous or lymphatic, should not alter the staging.

X. CLASSIFICATION OF CERVICAL TUMORS⁷

A. EPITHELIAL TUMORS
(Modified WHO histological classification)

1. Squamous cell carcinoma

a. Microinvasive squamous cell carcinoma
b. Invasive squamous cell carcinoma

1. Large cell keratinizing
2. Large cell non-keratinizing
3. Small cell type

c. Verrucous carcinoma
d. Warty (Condylomatous) carcinoma
e. Papillary squamous cell (Transitional) carcinoma
f. Lymphoepithelioma-like carcinoma

2. Adenocarcinoma

a. Mucinous adenocarcinoma

1. endocervical type
2. intestinal type
3. signet-ring type

b. Endometrioid adenocarcinoma

1. Endometrioid adenocarcinoma with squamous metaplasia

c. Clear cell adenocarcinoma
d. Minimal deviation adenocarcinoma
e. Serous adenocarcinoma
f. Mesonephric carcinoma
g. Well-differentiated villoglandular adenocarcinoma

3. Other Epithelial tumors

a. adenosquamous carcinoma
b. glassy cell carcinoma
c. mucoepidermoid carcinoma
d. adenoid cystic carcinoma
e. adenoid basal carcinoma
f. carcinoid-like tumor
g. small cell carcinoma
h. undifferentiated carcinoma
i. clear cell adenosquamous carcinoma

B. MESENCHYMAL TUMORS AND MIXED EPITHELIAL-MESENCHYMAL

1. Leiomyosarcoma
2. Endocervical stromal sarcoma
3. Embryonal rhabdomyosarcoma
4. Alveolar soft-part sarcoma
5. Adenosarcoma
6. Malignant mixed mesodermal tumor

C. MISCELLANEOUS TUMORS

1. Primary malignant melanoma
2. Primary choriocarcinoma
3. Lymphoma
4. Leukemia
5. Primary germ cell tumor

XI. MANAGEMENT OF CERVICAL CANCER

A. GENERAL GUIDELINES
1. Cervical cancer is diagnosed by biopsy. In the presence of a gross lesion, there is no need for a Papanicolaou smear or a fractional curettage.
2. Cervical cancer is staged clinically.
3. If clinically indicated, proctosigmoidoscopy and cystoscopy should be done to rule out invasion.
4. Special work-ups may include computed tomography, magnetic resonance imaging, PET scan and bone scan.
5. Once the diagnosis of invasive cancer is made, the patient should be referred to a gynecologic oncologist.
6. In selected cases, primary Radical Hysterectomy with Pelvic Node Dissection must be performed by a gynecologic oncologist.
7. For advanced disease, concurrent chemotherapy and radiotherapy is the minimum standard of treatment. ^{(8,9,10,11,12)}
8. Primary total hysterectomy with or without bilateral salpingo-oophorectomy is NOT performed for a patient with cervical cancer. It is an inadequate surgery and would mean cutting through tumor. The prognosis is uniformly poor in this situation. Surgical cure is NOT obtained and the probability of curative radiotherapy is greatly diminished.¹⁴
9. The treatment of cervical cancer requires a multidisciplinary approach involving a gynecologic oncologist and a radiation oncologist.

REFERENCES:

• Available upon request