Cervical Cancer: Symptoms, Types, Causes and Treatment

Cervical cancer remains a significant public health challenge globally, despite being one of the most preventable forms of cancer. It affects women of all ages, but is especially common in low- and middle-income countries where screening and vaccination programs are less accessible. Understanding the symptoms, types, causes, and treatment options is crucial for prevention, early detection, and improved patient outcomes. This article provides a comprehensive, evidence-based overview of cervical cancer, synthesizing the latest research and clinical insights.

Symptoms of Cervical Cancer

Cervical cancer often develops silently, with symptoms typically emerging only after the disease has progressed. Early detection is essential, as timely intervention significantly improves survival rates and quality of life. Unfortunately, many women are unaware of the warning signs, leading to delayed diagnosis and treatment.

Symptom	Description	Prevalence/Impact	Source
Vaginal bleeding	Unusual, postcoital, or postmenopausal	Most common symptom	7
Vaginal discharge	Offensive, persistent	Frequent in later stages	7
Pelvic pain	Lower abdominal or pelvic discomfort	Common in advanced cases	7
Pain	Can be severe, includes pelvic/back	81-96% in advanced cases	2 4 5
Fatigue	Persistent tiredness	Most common after therapy	5
Insomnia	Difficulty sleeping	54-69% after therapy	2 5
Anorexia	Loss of appetite	72% in advanced disease	2
Urinary symptoms	Nocturia, frequency, incontinence	Noted after treatment	5
Constipation	Difficult or infrequent bowel movements	50% at palliative referral	2 5
Emotional distress	Anxiety, depression, poor wellbeing	33-52% depression rates	1 2 4

Table 1: Key Symptoms

Early vs. Advanced Symptoms

Cervical cancer's early symptoms are often subtle or mistaken for common gynecological issues. The most frequently reported early warning sign is abnormal vaginal bleeding, which can occur after intercourse, between periods, or after menopause. Offensive vaginal discharge and pelvic pain may also signal disease progression, but these signs often appear in more advanced stages 7.

Symptom Burden and Quality of Life

As cervical cancer advances, the symptom burden increases dramatically. Pain becomes a predominant complaint, with studies showing up to 96% of women with advanced disease reporting pain as their chief concern 2. Other significant symptoms include anorexia, insomnia, fatigue, urinary and bowel disturbances, and a general decline in wellbeing 2 5.

The impact extends beyond physical symptoms. Women with cervical cancer frequently experience emotional distress, depression, and anxiety, which are exacerbated by factors such as low socioeconomic status, lack of social support, and sexual inactivity 1. These symptoms, if left unaddressed, severely impair quality of life during and after treatment 1 4.

Persistent and Long-term Effects

Treatment for cervical cancer, especially radiotherapy and chemotherapy, can cause persistent symptoms. Lymphedema, menopausal symptoms, sexual worries, and pain during intercourse may develop or worsen after therapy and persist for months or years 4 5. Fatigue and sleep disturbances are also among the most common and bothersome long-term effects 5.

The Challenge of Communication and Diagnosis

Research highlights that many women are unaware of cervical cancer symptoms, leading to delays in seeking medical help. Even when symptoms are present, they may not be communicated effectively to healthcare professionals, emphasizing the need for better education and screening initiatives 3.

Types of Cervical Cancer

Cervical cancer is not a single disease but comprises several types, each with distinct cellular origins, behaviors, and prognoses. Understanding these differences is vital for guiding diagnosis and treatment decisions.

Type	Description	Frequency	Source
Squamous Cell Carcinoma (SCC)	Originates from squamous epithelial cells	~70-80% cases	6 9
Adenocarcinoma (ADC)	Arises from glandular (columnar) cells	~15-25% cases	6 9
Adenosquamous Carcinoma	Contains both squamous and glandular cells	Rare	6
Molecular Subtypes	Hypoxia, Proliferation, Differentiation, Immunoactive	Identified by scRNA-seq	10

Table 2: Types of Cervical Cancer

Squamous Cell Carcinoma (SCC)

SCC is the most common type of cervical cancer, accounting for 70–80% of cases. It develops from the squamous epithelial cells lining the ectocervix, often at the transformation zone—the area where squamous and columnar epithelium meet 6 7 9. SCC is primarily associated with high-risk HPV types, particularly HPV16 6.

Adenocarcinoma (ADC)

Adenocarcinoma arises from the glandular cells of the endocervix and constitutes about 15–25% of cervical cancers 6 9. While less common than SCC, its incidence has increased in recent decades. ADC is more strongly associated with HPV18 6.

Mixed and Rare Types

Adenosquamous carcinoma contains both squamous and glandular elements and is relatively rare. Other histological variants exist but are much less frequent 6.

Molecular and Genetic Subtypes

Recent advances in single-cell transcriptomics have revealed that cervical cancers can be further stratified into four molecular subtypes based on gene expression: hypoxia, proliferation, differentiation, and immunoactive. These molecular subtypes have prognostic significance, with hypoxic tumors associated with the worst outcomes and immunoactive tumors with the best survival rates 10.

Causes of Cervical Cancer

Cervical cancer is unique among cancers in that its primary cause is well-known and, in many cases, preventable. The interplay between viral infection, host risk factors, and genetic mutations underlies the pathogenesis of this disease.

Cause	Description	Relative Contribution	Source
Persistent HPV Infection	High-risk HPV types (esp. HPV16, HPV18)	~99% of cases	6 7 8 12 13 14
Co-factors	Early sexual activity, multiple partners, smoking, high parity, HIV, low SES	Increase risk	7 14
Genetic/Cellular Changes	Oncogenic mutations, E6/E7 oncoproteins	Essential in carcinogenesis	9 15 19

Table 3: Causes of Cervical Cancer

Human Papillomavirus (HPV) Infection

Persistent infection with high-risk types of HPV is the central cause of cervical cancer, responsible for approximately 99% of cases worldwide 6 12 13 14. HPV is a common sexually transmitted virus, but only certain oncogenic strains—mainly HPV16 and HPV18—cause malignant transformation of cervical cells 6 7 8 12 13.

Other high-risk types implicated include HPV31, 33, 35, 39, 45, 51, 52, 56, 58, and 59, among others, although these are less frequent 6 8. The virus disrupts normal cell cycle control via its early proteins (notably E6 and E7), which inactivate tumor suppressor proteins and promote genetic instability 15 19.

Additional Risk Factors

While HPV infection is necessary for the development of cervical cancer, it is not sufficient by itself. Several co-factors increase the risk:

• Early onset of sexual activity (especially before age 16)
• Multiple sexual partners
• Cigarette smoking
• High parity (multiple pregnancies)
• Low socioeconomic status
• Poor genital hygiene
• Chronic immune suppression (e.g., HIV infection) 7 14

These factors can affect the persistence of HPV infection and the likelihood of progression to cancer.

Molecular Pathogenesis

HPV’s E6 and E7 oncoproteins play a key role by inactivating p53 and Rb tumor suppressor proteins, leading to uncontrolled cell division and accumulation of genetic mutations 15. Additional genetic changes, including mutations in oncogenes and tumor suppressor genes, further drive the transformation of normal cervical cells into cancerous ones 9 15 19.

Treatment of Cervical Cancer

The management of cervical cancer has evolved significantly, with treatment tailored to disease stage, patient health, and fertility considerations. Multimodal therapies, including surgery, radiotherapy, chemotherapy, and emerging targeted and immunotherapies, offer hope for improved survival and quality of life.

Treatment	Indication/Stage	Key Features/Outcomes	Source
Surgery	Early-stage, low-risk	Fertility-sparing options available	14 19
Radiotherapy	Early/locally advanced, adjuvant	IMRT reduces toxicity, includes brachytherapy	14 18
Chemoradiation	Locally advanced/high-risk	Improves survival, standard for IB3-IVA	14 18
Chemotherapy	Advanced/metastatic, palliative	Platinum-based regimens, variable efficacy	16 17 20
Targeted Therapy	Advanced/recurrent	Bevacizumab (anti-VEGF), TKIs	14 16 19 20
Immunotherapy	Advanced/recurrent (experimental)	Checkpoint inhibitors, ongoing trials	16 19

Table 4: Treatment Modalities

Surgery

For early-stage cervical cancer, surgery is often curative. Procedures range from local excision and conization (for very early disease) to radical hysterectomy. Where possible, fertility-preserving surgeries are offered to women desiring future pregnancies 14 19.

Radiation Therapy

Radiation therapy is a mainstay for both definitive and adjuvant treatment. Advanced techniques like intensity-modulated radiation therapy (IMRT) help reduce acute and late toxicity. Brachytherapy—internal radiation—remains essential for achieving local control and cure 18.

Chemoradiation

Concurrent chemoradiation (combining radiation with chemotherapy, usually cisplatin) is the standard of care for locally advanced disease (stages IB3-IVA) and for high-risk patients after surgery. This approach significantly improves survival 14 18.

Chemotherapy

For metastatic or recurrent cancer, systemic chemotherapy—often platinum-based—is the primary option. Although effective for symptom control, outcomes remain poor, with limited survival benefits. Single agents beyond first-line therapy have restricted efficacy 16 17 20.

Targeted and Novel Therapies

Advances in molecular biology have enabled the development of targeted therapies, particularly for advanced or recurrent cancers. Bevacizumab, an anti-VEGF agent, has improved survival when combined with chemotherapy and is now approved for first-line use in metastatic disease 14 16 19 20. Tyrosine kinase inhibitors (TKIs) and other agents targeting angiogenesis and the PI3K/AKT/mTOR pathways are being investigated 16 19.

Immunotherapy

Checkpoint inhibitors (e.g., anti-PD-1, anti-CTLA-4 antibodies) represent a promising frontier, with ongoing clinical trials evaluating their efficacy in advanced cervical cancer 16 19. Preliminary results are encouraging, especially for patients with immunoactive molecular subtypes 10.

Supportive and Palliative Care

Symptom management is essential throughout the disease trajectory. Multidisciplinary palliative care addresses pain, emotional distress, and other burdensome symptoms, improving quality of life for women with advanced or recurrent disease 2 4.

Conclusion

Cervical cancer is a largely preventable disease with a well-understood cause, clear risk factors, and effective treatments—when detected early. However, challenges remain in awareness, timely diagnosis, and access to care, especially in low-resource settings. Ongoing advances in molecular biology, targeted therapies, and immunotherapy offer hope for improved outcomes, even in advanced disease.

Key Takeaways:

• HPV infection is the primary cause of nearly all cervical cancers, with HPV16 and HPV18 being the most common high-risk types 6 7 12 13 14.
• Symptoms are often silent at first; abnormal vaginal bleeding is the most common early warning sign, while advanced disease brings pain, fatigue, and emotional distress 2 4 5 7.
• Cervical cancer includes several types—mainly squamous cell carcinoma and adenocarcinoma—with different risk profiles and treatment responses 6 9 10.
• Treatment depends on stage and includes surgery, radiotherapy (with or without chemotherapy), and palliative care. Targeted therapies and immunotherapies are emerging for advanced and recurrent disease 14 16 18 19 20.
• Prevention through HPV vaccination and screening remains the most effective strategy to reduce the global burden of cervical cancer 7 12 13 14.

Empowering women with knowledge and access to prevention, screening, and treatment is crucial for eliminating cervical cancer as a public health problem in the 21st century.