Diagnosis of a primary vaginal cancer is rare because most of these lesions will be
metastatic from another primary site. Although cancer of the vagina is more common
in postmenopausal women, an increase in young women being diagnosed with primary
vaginal cancer has been reported, especially in countries with a high HIV prevalence.
This will be associated with persistence of high-risk
HPV infection. The emphasis
should be on primary prevention with prophylactic HPV vaccination. Once there is a
suspicion of a primary vaginal cancer, this should be confirmed histologically with
biopsy. Staging has been done clinically, similar to cervical cancer; however, there is a
role for imaging in assisting with staging as this is often a difficult assessment.
Treatment should be individualized and depends on stage as well as histologic subtype.
It is prudent to refer cases to centers of excellence with experience in dealing with this
rare gynecological cancer.
Adenocarcinoma; FIGO Cancer Report; HPV; Imaging techniques; Individualized treatment;
Sarcoma; Staging; Vaginal cancer

Primary vaginal cancer is rare, constituting only 1%–2% of all female
genital tract malignancies and only 10% of all vaginal malignant
neoplasms.1 It is strictly defined as a cancer found in the vagina
without clinical or histologic evidence of cervical or vulvar cancer,
or a prior history of these cancers within five years.2 To support
this, most suspicious lesions of malignancy in the vagina will correspond
to metastatic lesions of cervical or vulvar cancer, or others
metastasizing to the vagina (e.g. breast, endometrium, trophoblast,
ovary, lymphoma).
Historically these cancers are more common in elderly and postmenopausal
women. If vaginal malignancy is found in younger women,
it is etiologically linked to cervical cancer, specifically with regard to the
persistence of high-risk
HPV infections.3 Vaginal cancers, although rare,
are increasingly being seen in younger women owing to the increase in
persistent high-risk
HPV infections, especially in settings with a high
HIV prevalence.
The vagina is an elastic muscular tube comprising many mucosal folds.
It extends from the cervix of the uterus to the hymenal ring, posterior
to the bladder and anterior to the rectum. Its elasticity and dimensions
vary depending on a woman’s age, parity, previous surgeries,
and hormonal status. Such characteristics can make proper examination
(limited by pain or narrowness of the introitus) and identification
of small malignant lesions difficult.
3.1 | Primary prevention (vaccination)
As with premalignant cervical lesions and carcinoma of the cervix,
persistent HPV infection—particularly the HPV 16 subtype—has
been associated with the long-term
development of high-grade
intraepithelial lesion (HSIL) and carcinoma of the vagina.4–6 The introduction of HPV vaccination as a primary prevention strategy in
cervical cancer has also been shown to reduce the prevalence of noncervical
premalignant lesions among vaccinated women.7 Long-term
trends analyses from the Norwegian Cancer Register also show promising
estimates of reduction in HPV-associated
cases of vaginal cancer
in future years among HPV-vaccinated
3.2 | Secondary prevention (screening)
There is no evidence to indicate routine screening for vaginal cancer
after hysterectomy for benign disease. If a hysterectomy has been
performed for persistent HSIL after repeated excisional procedures of
the cervix, vault smears are recommended for long-term
In those cases where screening for vaginal cancer is indicated, HPV
tests adequately correlate with cytological findings.11 Independently
of that, co-testing
seems to offer better accuracy in the diagnosis of
recurrent disease—as observed during follow-up
after treatment of
premalignant cervical lesions.12
3.3 | Tertiary prevention (management of
precancerous lesions)
As the majority of vaginal cancers are of squamous histology, a common
etiology is shared with cervical cancer. This is the persistence
of high-risk/
oncogenic HPV infections. Co-factors
include immunosuppression
and cigarette smoking. Smoking in combination with
HPV increases the risk of progression to vaginal HSIL when
compared with nonsmokers.13
The terminology for precancerous HPV-associated
vaginal lesions
has changed over time. In 2014, the WHO classification replaced the
classification used previously (VAIN 1–3) with squamous
intraepithelial lesion (SIL). This is divided into two categories: low
grade (LSIL) and high grade (HSIL). LSIL (VAIN 1) may be associated
with either low-risk
or high-risk
HPV and it represents productive
or transient infections that may regress. In contrast, HSIL represents
transforming high-risk
infections (previously VAIN 2–3).14
Women with HSIL are usually asymptomatic and the majority of
women are aged over 60 years. HSIL can be seen in younger women,
especially in immunocompromised individuals (HIV and transplant
patients). Colposcopy with acetic acid and/or Lugol iodine is indicated
if a woman has an abnormal vaginal cytological smear and no gross
abnormality. Biopsies of colposcopically abnormal areas (acetowhite
areas with punctation and/or punctation and mosaicism) is essential
for the diagnosis.
Risk of progression of HSIL to invasive cancer has been found to
range between 2% and 12%.15,16
Treatment of precancerous lesions of the vagina must be individualized.
Biopsy proven LSIL lesions can be followed up with observation
only (repeat smears and colposcopy), especially if women have non-oncogenic
strains of HPV.
The various modalities of treatment for HSIL lesions include laser
ablation, surgical excision, and topical treatments such as imiquimod and
topical chemotherapy with 5-fluorouracil
(5FU). Choice of treatment
depends on the number and location of the lesions, and the degree of
suspicion for an invasive cancer, as well as the availability of various
treatment options, cost of treatment, and skill of the treating doctor.
3.3.1 | Surgical excision
The advantages of excising HSIL of the vagina is that it provides a
pathological description of the tissue removed, especially when there
is a suspicion of microinvasion on colposcopic evaluation. Most HSIL
lesions are in the vault or upper third of the vagina and excision is ideal
in this situation.17 Morbidity can be associated with the proximity of
structures such as the bladder and rectum, as well as associated dyspareunia
as a result of vaginal shortening and stenosis. Women should
be extensively counselled preoperatively.
3.3.2 | CO2 laser vaporization
Laser vaporization is an alternative option to excision, especially for multifocal
lesions. Since there is no histologic specimen with this procedure, it
is imperative to ensure that there is no concern regarding cancer.18,19
3.3.3 | Topical fluorouracil
Topical application of 5FU has been used in an effort to avoid the
mutilating adverse effects of excision and laser ablation. Older studies
have shown comparable efficacy to laser and excision20,21. However,
these are retrospective in nature with small numbers. More recent
studies have shown inferior efficacy.15,22 A recent retrospective study
reviewed recurrence rate in 576 women treated with topical 5FU,
excision, or laser ablation. The statistically significant factors that contributed
to recurrence and progression were the presence of high-risk
HPV positivity and treatment modality. Laser and excision were found
to be superior to topical management with 5FU in reducing recurrences.
It was also found that laser was more effective than excision in
reducing recurrences of multifocal lesions, whereas surgical excision
was preferable with unifocal HSIL.23
3.3.4 | Topical 5% imiquimod
Imiquimod (applied topically either in creams or drug-embedded
tampons) is an immune response modulator that activates the innate
immune response and subsequently induces proinflammatory factors
such as interferons. It provides an alternative noninvasive and
safe method of treating women with vaginal HSIL, especially young
women with multifocal lesions or older women who wish to avoid
surgical modalities. Studies on imiquimod are few, but a recent randomized
controlled trial (RCT) as well as a systematic review and meta-analysis
(including this RCT) found that this is a safe and effective
treatment with regression rates similar to laser. HPV clearance rates
were greater than 50%, which was superior to laser.24,25
In general, independent of therapy chosen, most patients require
more than one therapy for adequate control. Since recurrence rate
is high with any single therapy, close and extended follow-up
is recommended in all cases. As in treated premalignant cervical lesions,
both HPV testing and cytology are recommended.
Women usually present with bleeding or an odorous discharge.
Locally advanced disease may result in pain as well, and symptoms of
disseminated disease depend on the site of metastases.
Diagnosis of vaginal cancer is made with directed biopsy of the
lesion and a clinical assessment that ensures there is no evidence of
tumor on the cervix or the vulva. Biopsy can be performed in an outpatient
setting; however, sometimes examination under anesthesia is
required for diagnosis and adequate assessment, particularly in young
girls and elderly women where the exam can become painful or limited
by narrowness of the introitus.
As primary vaginal cancer is rare, treatment is complex, often individualized,
and much of the management is extrapolated from cervical
cancer owing to its similar etiology and anatomical location. It is thus
recommended that women diagnosed with primary vaginal cancer are
referred to a tertiary unit whenever possible. Accordingly, outcomes
are influenced by the experience of the medical team in treating this
type of rare tumor.26
5.1 | Direct extension
A vaginal tumor may extend to the surrounding pelvic soft tissue
structures, including paravaginal tissue, parametria, urethra, bladder,
and rectum. Most tumors occur in the upper third of the vagina, especially
the posterior wall.
5.2 | Lymphatic spread
The lymphatic drainage of the vagina is complex. The upper vagina
drains by lymphatics to the pelvic lymph nodes. This includes the
obturator, internal iliac (hypogastric), and external iliac nodes. Spread
to the para-aortic
lymph nodes is rare. The lower vagina drains to the
inguinal and femoral nodes (groin nodes). Cancer in the mid-vagina
may follow both pelvic and groin node routes.27
5.3 | Hematogenous spread
Hematogenous dissemination to lung, liver, and bone are usually late
The predominant histologic subtype in primary vaginal cancer is squamous
carcinoma, which comprises 90% of cases. Adenocarcinoma
accounts for about 8%–10% of cases. Lymphomas, sarcomas, and
melanomas of the vagina are extremely rare.
All malignancies must be confirmed histologically. Since 80% of
cases are metastatic or secondary tumors, it is important to ensure
that there is no other primary site by careful examination and appropriate
investigations. Although biopsy can be obtained under local
anesthesia, in many instances examination under sedation or general
anesthesia should be performed to undertake an adequate exam and
obtain a biopsy.
By definition, tumors in the vagina that touch or extend to the
external os of the cervix should be classified as cervical cancer.
1. GX: Grade cannot be assessed.
2. G1: Well differentiated.
3. G2: Moderately differentiated.
4. G3: Poorly or undifferentiated.
Vaginal carcinoma is primarily clinically staged. This is based on
the results of a physical exam, biopsy, and imaging tests performed
before treatment selection. The 2009 FIGO staging for primary
vaginal cancer is described and compared with other systems
in Table 1.
Vaginal cancer is currently staged clinically, as is cervical cancer.
Modern imaging techniques such as computed tomography (CT),
magnetic resonance imaging (MRI), and positron emission tomography
(PET) are encouraged to guide management; however, these
tests should not be used to change the initial clinical staging.28 In
this regard, the FIGO Gynecologic Oncology Committee recommends
that wherever available, imaging should be used to better
define tumor volume and extension of disease. The Committee also
encourages registering of imaging findings and their influence on
therapeutic decisions as a complement of assigned clinical FIGO
stage. This will allow further analyses that could change the current
staging system.
9.1 | Magnetic resonance imaging
As extrapolated from cervical cancer, MRI is more sensitive in detecting
tumor size, as well as paravaginal or parametrial involvement.29,30
In primary vaginal tumors, clinical assessment may be difficult and
MRI may be a useful tool in individual cases owing to its superior soft
tissue resolution.