Vaginal Cancer

What is Vaginal Cancer?

Vaginal cancer is a rare but serious malignancy originating in the tissues of the vagina, the muscular canal that forms part of the female reproductive system. Anatomically, the vagina extends from the external genitalia (vulva) to the cervix, serving as the conduit for menstrual flow, sexual intercourse, and childbirth. It is composed of stratified squamous epithelium supported by elastic connective tissue and smooth muscle fibres, allowing for both structural integrity and flexibility. Despite being a lesser-known site for gynecologic cancers, the vagina plays a critical role in reproductive health and serves as a pathway connecting external and internal genital organs.

The primary function of the vaginal lining is to act as a physical barrier and immunologic interface, protecting internal reproductive organs from pathogens. It maintains an acidic pH through lactobacilli-mediated glycogen metabolism, which inhibits microbial overgrowth. Hormonal regulation, primarily by estrogen, affects the thickness, lubrication, and resilience of the vaginal epithelium, particularly during different life stages such as puberty, menstruation, pregnancy, and menopause.

Vaginal cancer develops when genetic mutations in the vaginal epithelial or glandular cells lead to uncontrolled cellular proliferation, evasion of apoptosis (programmed cell death), and accumulation of DNA damage. These malignant cells can form localised tumours, infiltrate adjacent pelvic structures such as the bladder or rectum, and, in advanced stages, metastasise to distant organs via the lymphatic or hematogenous routes. The malignancy may also spread to nearby lymph nodes, particularly those in the pelvic and inguinal regions.

Vaginal cancer is classified based on the cell type from which it originates. The main histological subtypes include:

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• Squamous Cell Carcinoma: Accounting for nearly 80–85% of all vaginal cancers, this type arises from the squamous epithelium lining the upper vagina. It typically occurs in postmenopausal women and has a gradual progression, often preceded by vaginal intraepithelial neoplasia (VAIN).
• Adenocarcinoma: Comprising 5–10% of cases, this subtype originates from the glandular cells and tends to occur in younger women. A rare subtype, clear cell adenocarcinoma, has been associated with prenatal exposure to diethylstilbestrol (DES), a synthetic estrogen once prescribed to pregnant women in the mid-20th century.
• Melanoma and Sarcoma: These are extremely rare but aggressive forms of vaginal cancer. Melanomas tend to affect the distal third of the vagina and often present as darkly pigmented lesions, whereas sarcomas arise from connective tissue and include variants such as rhabdomyosarcoma.

Although vaginal cancer is uncommon, its incidence increases with age, and it primarily affects women over the age of 60. However, certain risk factors can lead to earlier onset, such as persistent infection with high-risk human papillomavirus (HPV) types, particularly HPV-16 and HPV-18, which are strongly linked to the development of squamous cell carcinoma. Other contributing factors include a history of cervical cancer or intraepithelial neoplasia, immunosuppression (e.g., HIV infection), smoking, chronic vaginal irritation, and exposure to DES in utero.

In recent years, heightened awareness about HPV and the introduction of the HPV vaccine have sparked a renewed focus on early detection and prevention. Routine gynaecological screenings, including Pap smears and HPV testing, have improved the identification of precancerous changes. Additionally, the increased use of colposcopy and biopsy in evaluating abnormal vaginal lesions has facilitated earlier diagnosis, leading to better treatment outcomes.

Globally, vaginal cancer remains a rare diagnosis, accounting for less than 2% of all gynecologic cancers. According to GLOBOCAN 2020 estimates, its incidence is relatively low, but it is often underdiagnosed, particularly in low-resource settings. In India and other developing countries, limited access to routine pelvic exams and HPV vaccination programs may contribute to delayed diagnoses and poorer prognoses. Rural populations, where awareness and screening initiatives are minimal, face the highest risk of late-stage presentation.

Moreover, in postmenopausal women who may no longer undergo regular gynecologic check-ups, early symptoms of vaginal cancer. Symptoms such as abnormal bleeding, watery discharge, or pelvic pain are often misattributed to age-related changes. This diagnostic delay reinforces the need for targeted education and geriatric-focused cancer screening strategies.

As with many cancers, early-stage vaginal cancer is highly treatable, often with surgery or localised radiation therapy. However, once the disease progresses to involve regional nodes or distant organs, treatment becomes more complex, and prognosis worsens. Current research in molecular genetics and HPV-driven oncogenesis is paving the way for more personalised therapeutic approaches, including immunotherapies and targeted radiation protocols

Detailed Development and Progression of Vaginal Cancer

Vaginal cancer begins when normal cells lining the vaginal wall undergo genetic mutations that disrupt regular cell growth and death cycles. These changes are most commonly seen in the squamous epithelium, although glandular or melanocytic cells can also be affected. The most significant contributing factor is persistent high-risk HPV infection, especially HPV-16 and HPV-18. These viruses integrate into host DNA and trigger the expression of E6 and E7 oncogenes, which inactivate tumour suppressor proteins p53 and Rb.

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Other mutations and contributing risk factors include:

• TP53 – Associated with aggressive or poorly differentiated tumours
• PIK3CA and PTEN – Implicated in cell survival and proliferation pathways
• DES exposure in utero – Specifically linked to clear cell adenocarcinoma
• Smoking and immunosuppression – Known to exacerbate HPV persistence and mutation risk

These alterations can either be acquired over time or, rarely, related to environmental exposures such as diethylstilbestrol (DES) during fetal development.

Stages of Development

Initiation

The process begins with precancerous changes in the vaginal epithelium, typically classified as Vaginal Intraepithelial Neoplasia (VAIN). In these early stages, cells begin to lose their normal structure and behaviour but remain confined to the surface layer.

• VAIN I–III: Reflects increasing degrees of dysplasia, with VAIN III (carcinoma in situ) having the highest risk of progression
• Often asymptomatic and detectable only through pelvic exams or colposcopy
• Regression is possible in early VAIN, especially in younger or immunocompetent women

Promotion

If these dysplastic cells persist, they may eventually invade deeper layers of tissue, crossing the basement membrane to form invasive cancer. At this stage:

• The tumor starts to enlarge and form an ulcer, mass, or irregular lesion on the vaginal wall
• Local symptoms such as bleeding after intercourse, unusual discharge, or pelvic pain may begin to appear
• Surrounding tissues like the bladder, urethra, rectum, or cervix may become involved, depending on tumour location
• Still, some cases remain undetected due to nonspecific symptoms or postmenopausal status

Progression

As vaginal cancer progresses, it spreads both locally and systematically. This progression varies with the histological type:

• Squamous Cell Carcinoma: The most common type, typically slow-growing and follows a stepwise progression from VAIN. It spreads first to the inguinal or pelvic lymph nodes, depending on tumour location.
• Adenocarcinoma: Often more aggressive than squamous cell carcinoma and may present at a more advanced stage. Clear cell variants progress silently and are frequently linked to DES exposure.
• Melanoma: Rare but highly aggressive, with early hematogenous spread. Frequently diagnosed late and located in the distal vagina.
• Sarcoma (e.g., Rhabdomyosarcoma): Affects younger females and exhibits rapid progression with early local and systemic involvement.

Structural and Functional Impact

As the cancer advances, it causes both anatomical distortion and physiological disruption, especially when adjacent pelvic organs are affected.

Structural:

• Tumor mass effect may obstruct the vaginal canal or impinge on neighboring structures
• Extension into the bladder or rectum may result in fistulas, urinary retention, or rectal bleeding
• Pelvic wall invasion leads to deep-seated pelvic pain, sciatic nerve involvement, and limited mobility

Functional:

• Advanced tumours can impair sexual function and cause chronic discomfort
• Radiation therapy, often used in treatment, can lead to vaginal stenosis, dryness, and loss of elasticity
• In some cases, surgery may require partial or complete vaginectomy, resulting in significant psychological and functional implications
• Lymphatic spread may cause lower limb swelling (lymphedema) if inguinal or pelvic nodes are involved

Types of Vaginal Cancer

Vaginal cancer is categorized into several histological subtypes, each with distinct origins, clinical behaviors, and therapeutic considerations.

1. Squamous Cell Carcinoma (SCC)

• Most common type (~80–85% of cases).
• Arises from the squamous epithelial lining of the vagina, often preceded by Vaginal Intraepithelial Neoplasia (VAIN).
• Strongly associated with persistent high-risk HPV infection, particularly HPV-16.
• Typically occurs in postmenopausal women and progresses slowly.
• Early-stage tumours have favourable outcomes with radiation or surgical treatment.

2. Adenocarcinoma

• Represents 5–10% of vaginal cancers.
• Originates from glandular epithelial cells, often located in the upper third of the vagina.
• Includes clear cell adenocarcinoma, which is linked to in utero exposure to diethylstilbestrol (DES).
• Tends to occur in younger women exposed to DES or in older women with no known risk factors.
• May have a more aggressive clinical course and a higher risk of distant metastases.

3. Melanoma

• Accounts for 1–3% of vaginal malignancies.
• Originates from melanocytes, usually found in the lower third of the vagina, particularly on the anterior wall.
• Frequently pigmented but can also present as amelanotic (non-pigmented), making diagnosis difficult.
• Known for its aggressive nature, with early hematogenous spread to distant organs.
• Prognosis is generally poor due to late detection and resistance to conventional therapies.

4. Sarcoma (Including Rhabdomyosarcoma)

• Comprises <5% of vaginal cancers.
• More common in children and adolescents, especially embryonal rhabdomyosarcoma (sarcoma botryoides).
• Appears as a grape-like, polypoidal mass protruding from the vaginal opening.
• Rapidly growing and highly malignant, but may respond well to a combination of surgery, chemotherapy, and radiation.

5. Primary Vaginal Lymphoma

• Extremely rare and typically non-Hodgkin’s B-cell type.
• Presents as a vaginal mass or abnormal bleeding, often mistaken for more common gynecologic tumors.
• Diagnosis is confirmed by biopsy and immunophenotyping.
• Treatment involves systemic chemotherapy, sometimes followed by localised radiation.

Histopathology of Vaginal Cancer

Histologically, vaginal cancer presents distinct microscopic patterns that assist in diagnosis, classification, and treatment planning:

• Squamous Cell Carcinoma (SCC): Invasive nests and sheets of atypical squamous cells, intercellular bridges, keratin pearls (in keratinising type), and high mitotic activity.
• Adenocarcinoma: Gland-forming structures, often with clear or hobnail cells in clear cell subtype; tubulocystic and papillary patterns; sometimes associated with DES exposure.
• Melanoma: Large pleomorphic cells with melanin pigment (if pigmented), prominent nucleoli, and high mitotic index; amelanotic variants lack pigment and require special stains.
• Rhabdomyosarcoma: Small round blue cells in a myxoid stroma; cambium layer beneath vaginal epithelium is characteristic in sarcoma botryoides.
• Primary Vaginal Lymphoma: Sheets of atypical lymphoid cells with vesicular chromatin, frequent mitoses, and scant cytoplasm.

Immunohistochemical markers like p16 (HPV-related SCC), CEA (adenocarcinoma), HMB-45/Melan-A (melanoma), desmin/myogenin (rhabdomyosarcoma), and CD20 (lymphoma) aid in subtype identification and differential diagnosis.

Causes and Risk Factors

The exact cause of vaginal cancer is not fully understood, but several well-established risk factors contribute to its development:

• Human Papillomavirus (HPV) Infection: Persistent infection with high-risk HPV types—especially HPV-16 and HPV-18—is the most significant risk factor for squamous cell vaginal cancer.
• Age and Menopausal Status: Vaginal cancer is more frequently diagnosed in women over the age of 60, particularly postmenopausal women.
• Diethylstilbestrol (DES) Exposure: Women exposed to DES in utero (before birth) have a higher risk of developing clear cell adenocarcinoma of the vagina.
• Previous Gynecologic Cancers: A history of cervical or vulvar cancer increases the likelihood of vaginal cancer due to overlapping etiological factors like HPV.
• Smoking: Tobacco use weakens the immune response and increases DNA mutations, especially in HPV-positive individuals, heightening cancer risk.
• Weakened Immune System: Conditions like HIV/AIDS or long-term immunosuppressive therapy reduce the body’s ability to clear HPV infections, raising the risk of malignant transformation.
• Pelvic Radiation Therapy: Prior radiation treatment for other pelvic cancers can cause DNA damage in vaginal tissues, leading to secondary cancers.
• Chronic Irritation or Inflammation: Long-term use of vaginal devices (like pessaries) or untreated infections may contribute to cellular changes in the vaginal epithelium

Regional and National Context (India)

While vaginal cancer remains a relatively rare malignancy globally, its incidence in India is shaped by a unique interplay of socioeconomic, cultural, and healthcare access factors. The disease often goes underdiagnosed or is detected at a later stage due to limited awareness and inadequate screening infrastructure.

Symptoms of Vaginal Cancer

Many early-stage vaginal cancers are asymptomatic or cause mild symptoms that are often overlooked. As the disease advances, several signs may emerge that indicate the need for prompt medical evaluation.

1. Abnormal Vaginal Bleeding:
   Unexplained bleeding between menstrual periods, after sexual intercourse, or postmenopausally is the most common symptom. This bleeding may be light spotting or heavy hemorrhage.
2. Vaginal Discharge:
   Persistent watery, bloody, or foul-smelling vaginal discharge can be an early warning sign of vaginal cancer.
3. Pelvic Pain or Discomfort:
   Some women may experience a dull ache or pain in the pelvic area or lower abdomen, especially as tumors grow and press on nearby tissues.
4. Pain During Intercourse (Dyspareunia):
   Discomfort or pain during sexual activity can occur when the tumor affects the vaginal walls or surrounding nerves.
5. Lump or Mass in the Vagina:
   A palpable mass, growth, or ulceration inside the vagina may be noticed either by the patient or during a pelvic examination.
6. Urinary Symptoms:
   Difficulty urinating, frequent urination, or blood in the urine may occur if the cancer invades or compresses the urinary tract.
7. Bowel Changes:
   In advanced cases, bowel symptoms such as constipation or rectal bleeding may arise due to tumor involvement of the rectum or surrounding structures.
8. Swelling in the Legs:
   Blockage of lymphatic drainage by cancer can cause lymphedema, leading to swelling, especially in one or both legs.
9. Fatigue and Weight Loss:
   General symptoms such as unexplained fatigue, weakness, or weight loss may develop as the cancer progresses.

When to Seek Medical Attention

Recognizing when to seek medical attention is crucial for early diagnosis and effective treatment of vaginal cancer. Women should promptly consult a healthcare professional if they experience any of the following:

1. Unexplained Vaginal Bleeding:
   Bleeding between periods, after intercourse, or after menopause that is not normal or expected.
2. Persistent Vaginal Discharge:
   Any unusual, watery, bloody, or foul-smelling discharge lasting more than a few weeks.
3. Pain During Sexual Intercourse:
   New or worsening pain during sex, which may indicate an underlying problem.
4. Feeling a Lump or Mass in the Vagina:
   Any noticeable growth or mass inside the vagina that is unusual or persistent.
5. Pelvic or Lower Abdominal Pain:
   Continuous or worsening pain in the pelvic area that does not improve.
6. Changes in Urination or Bowel Habits:
   Difficulty urinating, blood in urine, constipation, or rectal bleeding.
7. Swelling in the Legs or Genital Area:
   Unexplained swelling may suggest lymphatic blockage.
8. General Symptoms Like Fatigue or Weight Loss:
   Unexplained tiredness, weakness, or weight loss, especially when accompanied by local symptoms.

Diagnosis of Vaginal Cancer

Diagnosis involves multiple steps to confirm malignancy and determine the extent of disease:

• Clinical and Physical Examination
  Comprehensive pelvic exam including visual inspection and palpation of the vagina, cervix, and surrounding tissues.
  Examination of inguinal and pelvic lymph nodes for enlargement or tenderness.
• Pap Smear and Cytology
  Vaginal cytology or Pap smear may detect abnormal or malignant cells, especially in cases involving the upper vagina or vaginal cuff post-hysterectomy.
• Biopsy
  A definitive diagnosis requires a tissue biopsy of the suspicious lesion or mass in the vagina.
  Histopathological analysis confirms cancer type and grade.
• Imaging Studies
  • MRI: Preferred for detailed assessment of tumor size, local invasion, and involvement of adjacent organs.
  • CT Scan: Useful for evaluating lymph node involvement and distant metastases.
  • PET-CT: Sometimes used for detecting occult metastases and staging.
  • Ultrasound: May assist in evaluating pelvic organs and lymph nodes.
• Laboratory Tests
  Blood tests to assess general health and organ function, although no specific tumor markers exist for vaginal cancer.
• Staging Procedures
  Additional diagnostic procedures, such as cystoscopy or proctoscopy, may be performed if bladder or rectal invasion is suspected.

Staging and Grading

Vaginal cancer staging follows the TNM system:
T (Tumor size and extent)
N (Regional lymph node involvement)
M (Distant metastasis)

• T Category: Describes the size of the primary tumor and how far it has invaded surrounding tissues, such as adjacent pelvic organs.
• N Category: Indicates whether cancer has spread to regional lymph nodes, commonly inguinal and pelvic nodes.
• M Category: Reflects the presence or absence of distant metastases, such as spread to lungs or liver.

Unlike some other cancers, vaginal cancer prognosis is heavily influenced by tumor size, depth of invasion, and nodal involvement rather than patient age. Early-stage tumors (T1) confined to the vaginal wall have a significantly better outcome compared to advanced stages with pelvic organ involvement or distant spread.

Age as a Modifier in Vaginal Cancer

• Younger Patients (Below 50 years): Tend to have a better overall prognosis and may tolerate aggressive treatments more effectively. Early detection in this group often leads to improved survival rates.
• Older Patients (Above 65 years): May have comorbidities that complicate treatment options and recovery. Advanced age can be associated with poorer outcomes due to delayed diagnosis and limited tolerance to aggressive therapies.
• Middle-aged Patients: Outcomes depend largely on tumour stage and overall health rather than age alone.

While age is considered during treatment planning, tumor characteristics and stage remain the primary determinants of prognosis in vaginal cancer.

Stage Overview

• Stage I:
  Tumor is confined to the vaginal wall without involvement of lymph nodes or distant metastasis.
• Stage II:
  Tumor invades the subvaginal tissue but has not spread to pelvic wall; may have minor regional lymph node involvement.
• Stage III:
  Tumor extends to the pelvic wall and/or involves regional lymph nodes.
• Stage IV:
  Tumor invades mucosa of the bladder or rectum and/or distant metastases are present.

Unlike anaplastic thyroid cancer, vaginal cancers do not have a specific anaplastic subtype, but advanced stages (III and IV) indicate aggressive disease requiring intensive treatment

Treatment Options

Treatment of vaginal cancer is tailored based on tumor type, stage, patient age, and overall health status.

1. Surgery
   • Local Excision: Removal of small, localized tumors, preserving vaginal structure.
   • Vaginectomy: Partial or total removal of the vagina for larger or invasive tumors.
   • Lymphadenectomy: Removal of regional lymph nodes if nodal involvement is confirmed.
2. Radiation Therapy
   • External Beam Radiation Therapy (EBRT): Commonly used for most stages, especially when surgery is not feasible or as adjuvant treatment.
   • Brachytherapy: Internal radiation delivered directly to the vaginal tissue, often combined with EBRT for improved local control.
3. Chemotherapy
   • Used in advanced stages or recurrent cases, often combined with radiation (chemoradiation).
   • Common agents include cisplatin and 5-fluorouracil.
4. Targeted and Immunotherapies
   • Emerging treatments for advanced or resistant vaginal cancer cases are under clinical investigation.
   • Currently limited but holds promise for future management.
5. Supportive Care
   • Focuses on symptom management, rehabilitation, and improving quality of life during and after treatment.

Prognosis and Survival Rates

Prognosis in vaginal cancer depends largely on the stage at diagnosis, tumor size, lymph node involvement, and overall patient health:

• Early-Stage Vaginal Cancer (Stage I):
  5-year survival rates are approximately 80–90% when the tumor is localized and treated promptly.
• Stage II:
  Survival rates decline to around 60–70% due to deeper tissue invasion or minor nodal involvement.
• Advanced Stages (Stage III-IV):
  5-year survival drops significantly, often below 40%, as the cancer spreads to pelvic walls, lymph nodes, or distant organs.
• Histological Type:
  Squamous cell carcinoma generally has a better prognosis than adenocarcinoma, which can be more aggressive.
• Early detection and timely, appropriate treatment greatly improve survival outcomes and quality of life.

Living with Vaginal Cancer

Living with vaginal cancer impacts both the physical and emotional dimensions of life. After diagnosis, patients may face challenges related to treatment side effects such as discomfort, changes in sexual function, and the psychological stress of coping with a cancer diagnosis. Comprehensive care that includes psychological counselling, pelvic floor rehabilitation, pain management, and connection to support groups is vital for improving quality of life.

Treatment and recovery extend beyond physical healing, requiring emotional adjustment as patients adapt to changes in body image, intimacy, and the possibility of long-term surveillance for recurrence. Regular follow-up visits and screenings are essential to monitor health and detect any signs of relapse early.

While vaginal cancer is rare, early detection and personalized treatment significantly enhance prognosis. If you experience unusual vaginal bleeding, pain, or discharge, seeking timely medical advice can lead to better outcomes. Education about the disease is important, but individualized care and support from healthcare professionals remain the cornerstone of living well with vaginal cancer

Need Expert Care for Vaginal Cancer?

Do not ignore persistent vaginal bleeding, unusual discharge, pain, or discomfort. Early intervention can be lifesaving. Consult cancer rounds today for a timely diagnosis and personalised treatment options tailored to your needs.

Disclaimer: This information is intended for educational purposes only and does not substitute professional medical advice. Always consult a qualified healthcare professional for diagnosis, treatment, and personalised guidance.