From the Guidelines
Cervical dysplasia is a precancerous condition that develops primarily due to persistent infection with high-risk human papillomavirus (HPV), particularly types 16 and 18, as supported by the most recent evidence 1. The pathophysiology begins when HPV infects the basal cells of the cervical epithelium, typically at the transformation zone where columnar epithelium meets squamous epithelium. Once inside the cell, viral oncoproteins E6 and E7 interfere with normal cellular functions by inactivating tumor suppressor proteins p53 and retinoblastoma protein (pRb), respectively. This disruption leads to uncontrolled cell proliferation, inhibition of apoptosis, and genomic instability. As the infection persists, abnormal cells accumulate genetic mutations and progressively replace normal epithelium, leading to varying degrees of dysplasia (mild, moderate, or severe). These changes are classified as cervical intraepithelial neoplasia (CIN) grades 1,2, or 3, reflecting the extent of abnormal cell growth. Without intervention, severe dysplasia may eventually progress to invasive cervical cancer as abnormal cells break through the basement membrane. Some key points to consider in the pathophysiology of cervical dysplasia include:
- The role of HPV in the development of cervical dysplasia, with types 16 and 18 being the most commonly associated with cervical cancer 1
- The importance of persistent HPV infection in the development of cervical precancerous lesions, such as CIN 1
- The potential for cervical dysplasia to progress to invasive cervical cancer if left untreated, with risk factors including smoking, immunosuppression, and long-term oral contraceptive use 1
- The benefits of cervical cancer screening in reducing the incidence and mortality of cervical cancer, including the use of HPV testing and Pap tests 1
- The potential harms of cervical cancer screening, including false-positive results and overtreatment of low-grade lesions 1.
Overall, the pathophysiology of cervical dysplasia is complex and multifactorial, involving the interplay of HPV infection, host immune response, and environmental risk factors. Understanding these factors is crucial for the development of effective prevention and treatment strategies for cervical dysplasia and cervical cancer.
From the Research
Pathophysiology of Cervical Dysplasia
The pathophysiology of cervical dysplasia is a complex process that involves the interaction of various factors, including human papillomavirus (HPV) infection, genetic alterations, and environmental factors.
- HPV Infection: HPV infection is a major risk factor for cervical dysplasia, with certain high-risk types such as HPV 16 and 18 being more strongly associated with the development of cervical cancer 2, 3, 4.
- Natural History of HPV Infection: The natural history of HPV infection is not fully understood, but studies suggest that most HPV infections are transient and clear spontaneously, while a small proportion persist and progress to cervical dysplasia and cancer 5.
- Risk Factors for Persistence: Persistent HPV infection, particularly with high-risk types, is a significant risk factor for the development of cervical dysplasia and cancer 3, 4.
- Type-Specific Associations: Different HPV types have varying associations with the risk of developing cervical dysplasia and cancer, with HPV 16 being one of the most strongly associated types 4.
- Viral Load: High viral load has been associated with an increased risk of developing cervical dysplasia and cancer, particularly for HPV 16 4.
- Multiple HPV Types: Infection with multiple HPV types has been detected in women with cervical dysplasia, suggesting a possible role for multiple types in the development or progression of the disease 6.
Progression to Cervical Cancer
Cervical dysplasia can progress to cervical cancer if left untreated.
- Regression and Progression: Cervical dysplasia can regress spontaneously, but a small proportion of cases progress to higher grades of dysplasia and eventually to invasive cancer 2, 3.
- Risk Factors for Progression: Persistent HPV infection, high viral load, and infection with high-risk HPV types are risk factors for progression to cervical cancer 3, 4.