Characteristic features of cervical cancer | Diagnosis | Epidemiology | Staging | Treatment & Survival | References

Cervical cancer is a relatively uncommon finding in comparison to the number of cases of CIN diagnosed annually in the US. In 2000, the incidence of invasive cervical cancer was estimated at 12,800 cases, and there were 4,600 cervical cancer related deaths. In other parts of the world that lack screening programs, cervical cancer is still the most common cancer among women. The major focus of colposcopic assessment of abnormal cervical cytology is to detect cancer. In order to accomplish this goal, one must maintain a high index of suspicion and stick with standard triage protocols such as assuring adequacy of the examination and a good correlation between cytology, colposcopy and biopsy findings.

Since cervical cancer is a relatively rare finding in a routine colposcopic practice, the colposcopist should be aware of the hallmark features of invasive cancer and look for these features with each patient they evaluate.

CHARACTERISTIC FEATURES OF CERVICAL CANCER

• Atypical vessels-non branching (e.g., commas, corkscrew, sausage shaped, hairpin)
• Abnormal vaginal bleeding or discharge
• Ulcerations
• Raised, irregular surface
• Yellow color to epithelium
• Firmness to palpation

As a cancer of the cervix develops, neovascularization occurs as the result of tumor angiogenic factor released by the cancer cells. These vessels do not follow the normal regular arborizing vessel pattern, but instead the new vessels have irregular course and caliber. They can run parallel to the surface of the cervical epithelium and form non-branching patterns such as corkscrews, squiggles and comma-shaped vessels. Routine use of a green filter can assist the colposcopist in assessing vessel patterns at the time of colposcopy.

DIAGNOSIS

Cytologically, squamous cell cancer can be either keratinizing or non-keratinizing. Cells can occur in syncytial-like clusters or singly, and demonstrate very irregular chromatin clumping, nucleoli, and may have a background tumor diathesis of blood and cellular debris. 

 

Cancer (cytology) (Liquid based-Papanicolaou stain x 400): Irregular cell forms; nuclei are enlarged with prominent nucleoli. The cell cluster at right shows diathesis (“cotton candy necrosis”).

 

Colposcopically, cervical cancer can be a challenge to diagnose, especially microinvasive cancer since atypical vessels or other signs of more advanced disease may not be present. This reinforces the fact that one must maintain a high degree of suspicion and effectively address any discrepancies between colposcopy, cytology and histology before therapy is initiated, particularly ablative therapy. Cervical cancer can be squamous, glandular or mixed type. Invasion is diagnosed when there is a breach in the basement membrane. If the invasion extends 3 mm or less, it is referred to as microinvasive disease. If invasion is greater than 3mm, it is frankly invasive cancer. 

 

Squamous cell carcinoma (H&E x 400): Irregular nests of malignant squamous cells in a fibrotic stroma (desmoplasia).

 

If biopsy or endocervical curettage reveals invasive cancer, a cone biopsy is not needed.

EPIDEMIOLOGY

There are approximately 11,000 new cases/year and around 4000 deaths/year in the United States.  There are >250,000 new cases of CIN 2,3 each year.  There are 2 major histological types of cervical cancer.  93% are squamous cell cancers and contain HPV DNA; 90% are subtypes 16/18, which are most virulent.  7% of cases are adenocarcinomas -- but these are on the rise.  Adenocarcinomas are associated with HPV type 18.

When considering preinvasive disease, the classic theory holds that SIL leads to squamous carcinoma although we now understand that most SIL, especially low-grade SIL, regress or remain stable for considerable periods. When SIL progress to invasive squamous cervical cancer, ISCC usually develops from an area of SIL located adjacent to the SCJ. Oncogenic HPV serves as initiators. Other factors relating to immune status such as cigarette smoking, nutrition, or Chalmydia infections may be promoters.  Adenocarcinoma develops from glandular atypia and may be preceded by an Atypical Glandular Cells of uncertain significance (AGC) Pap smear.  The only preinvasive stage is adenocarcinoma in situ (AIS).

 

Adenocarcinoma (H&E x 400): Irregularly shaped glands within a fibrotic inflamed stroma (desmoplasia). Cells are highly atypical; the nuclei contain prominent nucleoli.

 

The median age to develop cervical cancer is 45 to 50 years. Older women are often more susceptible due to lack of screening. Younger women have more problems with rapidly progressing disease. 50% of women diagnosed with invasive cancer have never had a Pap smear. 10% have not had a Pap smear in last 5 years.

STAGING OF CERVICAL CANCER

Stage 0	carcinoma-in-situ
Stage I	the tumor is confined to the cervix
	IA	microinvasive disease, with the lesion not grossly visible: no deeper than 5 mm and no wider than 7 mm
		IA1	invasion <3 mm and no wider than 7 mm
		IA2	invasion >3 mm but <5 mm and no wider than 7 mm
	IB	larger tumor than in IA or grossly visible, confined to cervix
		IB1	clinical lesion no greater than 4 cm
		IB2	clinical lesion greater than 4 cm
Stage II	extends beyond the cervix, but does not involve the pelvic side wall or lowest third of the vagina
	IIA	involvement of the upper 2/3 of vagina, without lateral extension into the parametrium
	IIB	lateral extension into parametrial tissue
Stage III	involves the lowest third of the vagina or pelvic side wall, or causes hydronephrosis
	IIIA	involvement of the lowest third of the vagina
	IIIB	involvement of pelvic side wall or hydronephrosis
Stage IV	extensive local infiltration or has spread to a distant site
	IVA	involvement of bladder or rectal mucosa
	IVB	distant metastases

 

TREATMENT AND SURVIVAL

Treatment of frankly invasive cancer usually consists of a radical hysterectomy with lymph node dissection, or radiation therapy with advanced disease. If the biopsy reveals microinvasive disease, a cone biopsy is required, since a biopsy alone is insufficient to rule out frankly invasive cancer, which may be adjacent to the biopsy site. If a cold cone or loop excision reveals microinvasive cervical cancer with clear margins, treatment can include a simple hysterectomy or, if the patient desires to maintain her fertility, observation with careful follow-up.

Stage IA—5-year survival 95%

• simple hysterectomy or careful observation after cone biopsy (with clear margins). 

Stage IB or IIA—5-year survival 70% to 85%

• radical hysterectomy with pelvic-node dissection, or
• external beam and intracavitary radiotherapy (equally effective)

Stage IIB, III, IVA—5-year survival 65%, 40%, 20% respectively

• pelvic radiotherapy
• Treatment with cisplatin-based chemotherapy should strongly be considered for patients receiving radiotherapy 14

Stage IVB—5year survival 10%

• chemotherapy with or without pelvic radiotherapy

REFERENCES

1. American College of Obstetricians and Gynecologists. Routine cancer screening. In: The ACOG (eds). 2001 Compendium of SelectedPublications. Washington DC: ACOG; 2000. p.233-7
2. ACOG Technical Bulletin. Diagnosis and Management of Invasive Cervical Carcinomas. Dec 1989;138:1-6.
3. NIH releases consensus statement on cervical cancer. Am Fam Phys  1996; 54:3210-16. 
4. Burger MPM, Hollemana H, Gouw ASH, Pieters WJ, Quint WG.  Cigarette smoking and human papilloma virus in patients with reported cervical cytological abnormality.  Br J Med 1993; 306:749-52.
5. Cannistra SA, Niloff JM. Cancer of the uterine cervix. NEJM 1996;334:1030-8.
6. Fink DJ. Change in American Cancer Society checkup guidelines for detection of cervical cancer. Cancer J Clin 1988;38:127-8.
7. Nelson JH, Averette HE, Richart RM. Cervical intraepithelial neoplasia (dysplasia and carcinoma in situ) and early invasive cervical carcinoma. Cancer 1990;39: 157-78
8. Rylander E. Cervical cancer in women belonging to a cytologically screened population. Acta Obstet Gynecol Scand 1976;S5:361-6.
9. Schiffman MH. Recent progress in defining the epidemiology of human papillomavirus infection and cervical neoplasia. J Natl Cancer Inst 1992;84:394-8.
10. Modern Colposcopy Textbook and Atlas, Second Edition. American Society for Colposcopy and Cervical Pathology. Kendall-Hunt Publishing Co., Dubuque, 2004. Chapter 3, 4, 5.

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