Vaginal cancer

Primary carcinomas of the vagina represent 2% to 3% of malignant neoplasms of the female genital
tract. In the United States, it is estimated that there will be 2,160 new cases diagnosed in 2009, and
770 deaths from the disease (1). More than 50% of patients are diagnosed in the seventh, eighth, and
ninth decades, and squamous cell histology accounts for about 80% of cases (2).
Until the late 1930s, vaginal cancer was in general considered to be incurable. Most patients
presented with disease that had spread beyond the vagina, and radiation therapy techniques were
poorly developed. With modern techniques for radiation therapy, cure rates of even advanced cases
should now be comparable with those for cervical cancer (3,4,5). According to the Annual Report,
the overall 5-year survival rate has increased from 34.1% in 1959 to 1963 to 53.6% in 1999 to 2001
(2).
Fu (6) reported that 84% of carcinomas involving the vagina were secondary, usually from the cervix
(32%); endometrium (18%); colon and rectum (9%); ovary (6%); or vulva (6%). Of 164 squamous cell
carcinomas, 44 (27%) were primary and 120 (73%) were secondary. Among the latter, 95 (79%)
originated from the cervix; 17 (14%) from the vulva; and 8 (7%) from the cervix and the vulva (6).
This apparent discrepancy is partly related to the International Federation of Gynecology and
Obstetrics (FIGO) classification and staging of malignant tumors of the female pelvis. The staging
requires that a tumor that has extended to the portio and reached the area of the external os should
be regarded as a carcinoma of the cervix, whereas a tumor that involves the vulva and vagina should
be classified as a carcinoma of the vulva. Endometrial carcinomas and choriocarcinomas commonly
metastasize to the vagina, whereas tumors from the bladder or rectum may invade the vagina
directly.
Primary Vaginal Tumors
The histologic types of primary vaginal tumors are shown in Table 14.1
(7,8,9,10,11,12,13,14,15,16,17,18,19). Squamous cell carcinomas are the most common, although
adenocarcinomas, melanomas, and sarcomas are also seen. Sarcomas occasionally follow radiation
therapy for cervical cancer.
Squamous Cell Carcinoma
Squamous cell carcinoma is the most common vaginal cancer. The mean age of the patients is
approximately 67 years, although the disease occasionally is seen in the third and fourth decades of
life (4,7,10,13). About 80% of patients are older than 50 years (2).
P.577


Table 14.1 Primary Vaginal Cancer: Reported Incidence of Histologic Types
Histologic Types Number Percentage
Squamous cell 1,054 82.6
Adenocarcinoma (including clear cell) 123 9.6
Melanoma 42 3.3
Sarcoma 40 3.1
Undifferentiated 8 0.6
Small cell 5 0.4
Lymphoma 4 0.3
Carcinoid 1 0.1
Total 1,277 100.0
Data compiled from Perez et al., 1974 (7); Pride and Buchler, 1977 (8); Ball and Berman, 1982 (9); Houghton and Iversen, 1982 (10);
Benedet et al., 1983 (11); Peters et al., 1985 (12); Rubin et al., 1985 (13); Sulak et al., 1988 (14); Eddy et al., 1991 (15); Ali et al.,
1996 (16); Tjalma et al., 2001 (17); and Tewari et al., 2001 (18), Hellman et al., 2006 (19).

Etiology
Women who have been treated for a prior anogenital cancer, particularly of the cervix, have a high
relative risk of developing vaginal cancer, although the absolute risk is low (20).
In a population-based study of 156 women with in situ or invasive vaginal cancer, Daling et al.
determined that they had many of the same risk factors as patients with cervical cancer, including a
strong relationship with human papilloma virus (HPV) infection (20). The presence of antibodies to
HPV 16 was strongly related to this risk. A study of 341 cases from the Radiumhemmet reported that
the disease seemed to be etiologically related to cervical cancer, and thus HPV infection, in young
patients, but in older patients, there was no such association (21).
As many as 30% of patients with primary vaginal carcinoma have a history of in situ or invasive
cervical cancer treated at least 5 years earlier (11,12,13). In a report from the University of South
Carolina, a past history of invasive cervical cancer was present in 20% of the cases and of cervical
intraepithelial neoplasia (CIN) in 7% (15). The median interval between the diagnosis of cervical
cancer and the diagnosis of vaginal cancer was 14 years, with a range of 5 years, 8 months to 28
years. Sixteen percent of the patients had a history of prior pelvic irradiation.
There are three possible mechanisms for the occurrence of vaginal cancer after cervical neoplasia:
Occult residual disease
New primary disease arising in an at-risk lower genital tract
Radiation carcinogenicity
In the first instance, extension of intraepithelial neoplasia from the cervix to the upper vagina was
not appreciated and an adequate vaginal cuff was not taken because vaginal colposcopy was not
performed before surgical management of the cervical tumor. Surgical margins of the upper vaginal
resection usually show in situ neoplasia, and these persistent foci eventually progress to invasive
disease. In the second instance, vaginal colposcopy is negative, and the surgical margins of resection
are free of disease.
There is controversy regarding the distinction between a new primary vaginal cancer and a recurrent
cervical cancer. Many authorities use a 5-year cut-off because 95% of cervical cancers will recur
within this period (22,23) but others prefer a 10-year interval (19).
Prior pelvic radiation therapy has been considered a possible cause of vaginal carcinoma (8). In the
series of 314 patients with squamous cell carcinoma of the vagina reported from Sweden, previous
pelvic radiation was reported by 44 patients (14%) on an average of 22 years earlier (range 5-55
years)(19). Judicious use of pelvic radiation may be particularly important in young patients, who
may live long enough to develop a second neoplasm in the irradiated vagina (24).