What is the overview of cervical cancer, including prevention, treatment, and screening?

Cervical Cancer Overview

Epidemiology and Etiology

Cervical cancer is the third most common cancer in women globally, with virtually all cases (99%) caused by persistent infection with high-risk human papillomavirus (HPV), making it an almost entirely preventable disease through vaccination and screening. 1

• HPV types 16 and 18 account for approximately 70% of all cervical cancers (HPV16: 55-60%, HPV18: 10-15%) 1
• Squamous cell carcinomas comprise 70-80% of cases, while adenocarcinomas account for 10-15% 1
• In the United States, cervical cancer incidence and mortality decreased by 75% and 74% respectively following introduction of cytology screening in 1949 1
• Approximately 12,170 new cases and 4,220 deaths occur annually in the United States 1

Primary Prevention: HPV Vaccination

HPV vaccination provides the most effective primary prevention against cervical cancer and should be administered before sexual debut for maximum efficacy. 2

• Vaccination protects against HPV types responsible for approximately 70% of cervical cancers 1
• Over 60 million doses distributed globally by 2010 in developed countries 1
• Vaccinated women must continue routine screening as long-term efficacy data and impact on screening intervals remain uncertain 1

Screening Recommendations

Age-Appropriate Screening Strategy

Women aged 21-65 years should undergo cervical cancer screening regardless of sexual history or HPV vaccination status, using one of three acceptable strategies: cytology alone every 3 years (ages 21-29), cytology alone every 3 years OR HPV testing every 5 years OR cotesting every 5 years (ages 30-65). 1

Ages 21-29 Years

• Screen with cervical cytology alone every 3 years 1
• HPV testing not recommended in this age group due to high prevalence of transient infections that resolve spontaneously 1

Ages 30-65 Years

• Three acceptable options: 1
  • Cytology alone every 3 years
  • Primary HPV testing alone every 5 years
  • Cotesting (cytology + HPV) every 5 years
• HPV DNA testing in conjunction with cytology recommended by the American Cancer Society for women ≥30 years 1

Screening Initiation and Cessation

• Do not screen women younger than 21 years regardless of sexual history, as screening causes more harm than benefit due to transient HPV infections and potential adverse effects of treatment on childbearing 1
• Discontinue screening at age 65 years only if adequate prior screening documented: 3 consecutive negative cytology results OR 2 consecutive negative HPV results within 10 years, with most recent test within 5 years 1
• Continue screening for at least 20 years after treatment of high-grade precancerous lesions, even if this extends past age 65 1

Special Populations

Women with HIV infection, compromised immune systems, in utero diethylstilbestrol exposure, or prior high-grade lesions require individualized screening with more frequent intervals, typically annually, and should not follow standard cessation guidelines. 1, 3

• Immunocompromised patients should receive annual screening rather than extended intervals 3
• Do not discontinue screening at age 65 if immunosuppression continues 3

Post-Hysterectomy

Women who have had hysterectomy with cervix removal and no history of high-grade precancerous lesions or cervical cancer should not be screened. 1

Screening Barriers and Failures

Half of all women diagnosed with cervical cancer in the United States have never been screened, and an additional 10% were not screened within 5 years of diagnosis. 1

• Cytology testing limitations account for approximately 30% of cervical cancers despite screening 1
• Provider errors in follow-up of abnormal results account for another 10% 1
• Barriers include fear, embarrassment, lack of knowledge, cultural factors, and systemic access issues 1

Pathology and Natural History

HPV Infection Dynamics

• Most HPV infections (approximately 90%) are transient and clear within 1-2 years 1
• Persistent HPV infection, especially HPV16, strongly predicts development of CIN3+ (20-30% risk over 5 years for persistent HPV16) 1
• Untreated CIN3 has 30% probability of progressing to invasive cancer over 30 years 1

Histologic Types

• Squamous cell carcinomas: 70-80% of cases 1
• Adenocarcinomas: 10-15% of cases (HPV18 causes higher proportion: 32% vs 8% for squamous) 1
• Neuroendocrine tumors and undifferentiated carcinomas comprise remaining cases 1

Treatment Approaches

Precancerous Lesions

High-grade cervical lesions (CIN2/3) should be treated with excisional or ablative therapies to prevent progression to invasive cancer. 1, 4

• Excisional therapies: Loop electrosurgical excision procedure (LEEP), cold-knife conization 4, 5
• Ablative therapies: Cryotherapy, laser ablation 1, 4
• Treatment of precancerous lesions is less invasive than cancer treatment and results in fewer adverse effects 1

Invasive Cancer

Early-stage cervical cancer may be treated with surgery (hysterectomy) or chemoradiation, while advanced disease requires multimodal therapy including chemotherapy, radiation, immunotherapy, and targeted therapy. 1, 4, 6

• Early-stage disease (detected through screening): 5-year survival approximately 91% 1
• Overall 5-year survival rate: approximately 68% 7
• Fertility-sparing options available for select early-stage patients desiring future childbearing 7

Management of Abnormal Screening Results

HPV testing is preferred over cytology for management of abnormal results because it provides more sensitive detection of cancer precursors and allows precise risk stratification. 5

• Follow American Society for Colposcopy and Cervical Pathology (ASCCP) 2019 risk-based management guidelines 5
• Risk-based strategies reduce unnecessary procedures in low-risk patients while focusing resources on high-risk patients 5
• Prompt referral to gynecologic oncology required if malignant lesion identified 7

Key Clinical Pitfalls

• Do not screen women under age 21 or over age 65 (with adequate prior screening) as harms outweigh benefits 1
• Do not assume HPV vaccination eliminates need for screening—vaccinated women require same screening as unvaccinated 1
• Do not use standard screening intervals for immunocompromised patients—these women need annual screening 3
• Do not stop screening at age 65 in women with history of high-grade lesions—continue for at least 20 years post-treatment 1, 3
• Ensure adequate follow-up of abnormal results, as provider errors in follow-up account for 10% of cervical cancers 1