Cervical intraepithelial neoplasia
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Maria Fernanda Villarreal, M.D. [2]
Synonyms and keywords: CIN; cervical interstitial neoplasia; cervical dysplasia; cervical interstitial neoplasia
Overview
Cervical intraepithelial neoplasia (also known as cervical dysplasia and CIN), is the potentially premalignant transformation and abnormal growth (dysplasia) of squamous cells on the surface of the cervix.[1] Cervical intraepithelial neoplasia was first discovered by Dr. Georgios Nikolaou Papanikolaou, a Greek pathologist, in 1927.[2] There are 4 cytological classifications for cervical intraepithelial neoplasia: Bethesda system, Papanicolaou classification, CIN nomenclature, and dysplasia nomenclature. The most common cytological classification systems for cervical intraepithelial neoplasia is the Bethesda and CIN nomenclature. Cervical intraepithelial neoplasia may be classified according to Bethesda system by cytology description into 3 subtypes: atypical squamous cells, low grade squamous intraepithelial lesion (LGSIL or LSIL), and high grade squamous intraepithelial lesion (HGSIL or HSIL). The pathogenesis of cervical intraepithelial neoplasia is characterized by the premalignant transformation and abnormal growth of squamous cells on the surface of the cervix.[3] The presence of human papillomavirus (HPV) has a crucial role in the pathogenesis of cervical intraepithelial neoplasia. The infection of human papillomavirus (HPV) leads to the first precursor lesion of cervical intraepithelial neoplasia, also known as the koilocyte, which is a squamous epithelial cell that has undergone a number of structural changes.
Historical Perspective
- Cervical intraepithelial neoplasia was first discovered by Dr. Georgios Nikolaou Papanikolaou, a Greek pathologist, in 1927.[2]
- In 1928, the first screening was developed by Aurel Babeș, a Romanian pathologist to diagnose cervical intraepithelial neoplasia.[2]
- In 1980, human papillomavirus (HPV) was first identified in the pathogenesis of cervical intraepithelial neoplasia.[4]
- In 1988, the Bethesda system classification method was introduced to categorize histopathological findings of cervical intraepithelial neoplasia according to degrees of severity.
Classification
- Cervical intraepithelial neoplasia has 4 cytological classifications: Bethesda system, Papanicolaou classification, CIN nomenclature, and dysplasia nomenclature.
- The most common classification systems for cervical intraepithelial neoplasia is the Bethesda and CIN nomenclature.
- Cervical intraepithelial neoplasia may be classified according to Bethesda system by cytology description into 3 subtypes:
- Atypical squamous cells
- Undetermined significance (ASC-US)
- Low grade squamous intraepithelial lesion (LGSIL or LSIL)
- High grade squamous intraepithelial lesion (HGSIL or HSIL)
- Cervical intraepithelial neoplasia may be classified according to CIN nomenclature by histological severity into 3 subtypes:
- Cervical intraepithelial neoplasia I (CIN I)
- Cervical intraepithelial neoplasia II (CIN II)
- Cervical intraepithelial neoplasia III (CIN III)
- Cervical intraepithelial neoplasia may be classified according to Papanicolau by cytology description into 5 subtypes:
- Class I: absence of atypical or abnormal cells
- Class II: atypical cytology, but no evidence of malignancy
- Class III: cytology suggestive of, but not conclusive for, malignancy.
- Class IV: cytology strongly suggestive of malignancy
- Class V: cytology conclusive for malignancy
- Cervical intraepithelial neoplasia may be classified according to dysplasia nomenclature by cytology description into 5 subtypes:
- Negative
- Squamous atypia
- Mild dysplasia
- Moderate dysplasia
- Severe dysplasia
- Carcinoma
- Other variants of cervical intraepithelial neoplasia include carcinoma in situ, typical glandular cells not otherwise specified, and invasive carcinoma.
Pathophysiology
- The pathogenesis of cervical intraepithelial neoplasia is characterized by the premalignant transformation and abnormal growth of squamous cells on the surface of the cervix.[3]
- Cervical intraepithelial neoplasia arises from cells localized in the ectoendocervical squamocolumnar junction (also known as the "transformation zone") of the cervix persistently infected human papillomavirus (HPV)
- The presence of human papillomavirus (HPV) subtypes 16 and 18 play an essential role in the pathogenesis of cervical cancer has a crucial role in the pathogenesis of cervical intraepithelial neoplasia.
- The first precursor lesion of cervical intraepithelial neoplasia is the koilocyte, which is a squamous epithelial cell that has undergone a number of structural changes (these usually occur as a result of infection of the cell by human papillomavirus).
- On gross pathology, there are no characteristic findings of cervical intraepithelial neoplasia.
- On microscopic histopathological analysis, findings of cervical intraepithelial neoplasia will depend on the lesion grade.
- The table below summarizes the histopathological findings of cervical intraepithelial neoplasia according to lesion grade.
| Cytologic findings Lesion grade |
Histologic changes Bethesda system |
Description | Microscopic findings |
|---|---|---|---|
| CIN I
Cervical intraepithelial neoplasia I |
|
|
_koilocytosis.jpg) |
| CIN II
Cervical intraepithelial neoplasia II |
|
|
_CIN2.jpg) |
| CIN III
Cervical intraepithelial neoplasia III |
|
|
_CIN3.jpg){kind=spacer} |
Molecular Pathogenesis
- The progression of cervical intraepithelial neoplasia usually involves the viral replication of human papillomavirus (HPV) following mutation of proteins E6/E7, resulting in the overexpression of these oncoproteins.
- The overexpression of these oncoproteins will lead to lead to a deficient cell replication and excessive cell growth. l
Causes
- The most important cause of cervical intraepithelial neoplasia is human papillomavirus (HPV)
- Low-risk type or non-oncogenic, include:
- Subtypes 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68, 69, 82
- High-risk type or oncogenic, include:
- Subtypes 6, 11, 40, 42, 43, 44, 54, 61, 72, 81
Differentiating Cervical Intraepithelial Neoplasia from Other Diseases
- Cervical intraepithelial neoplasia must be differentiated from other diseases that cause abnormal vaginal bleeding, dyspareunia, and abnormal vaginal discharge, such as:
- Cervicitis
- Vaginal cancer
- Vaginitis
- Paget disease
Epidemiology and Demographics
Prevalence
- The prevalence of cervical intraepithelial neoplasia is approximately 7.7 per 100,000 individuals in the United States.[5]
- The incidence of cervical intraepithelial neoplasia is approximately 8.1 cases per 100,000 women per year in the United States
Age
- The median age at diagnosis for cervical intraepithelial neoplasia is 30 years.
- Cervical intraepithelial neoplasia is more commonly observed among female patients between 20 to 40 years years old.
Race
- Cervical intraepithelial neoplasia usually affects more frequently individuals of the Hispanic race.
- Hispanic individuals are more likely to develop cervical intraepithelial neoplasia.
Risk Factors
- The most important risk factor in the development of cervical intraepithelial neoplasia is immunosuppression.
- Common risk factors in the development of cervical intraepithelial neoplasia are cigarette smoking, herpes simplex virus, chlamydia, oral contraceptives, and increased sexual activity.
Natural History, Complications and Prognosis
- The majority of patients with cervical intraepithelial neoplasia remain asymptomatic for years.
- Early clinical features include abnormal vaginal discharge, dyspareunia, and abnormal vaginal bleeding.
- If left untreated, the majority of patients with cervical intraepithelial neoplasia may progress to develop cervical cancer.
- Common complications of cervical intraepithelial neoplasia include infertility, maternal-fetal transmission of human papillomavirus, and recurrent human papillomavirus infection.
- Prognosis is generally good if detected on time, and the 5-year survival rate of patients with cervical intraepithelial neoplasia is approximately [#%].
Diagnosis
Diagnostic Criteria
- The diagnosis of cervical intraepithelial neoplasia is made when at least [number] of the following [number] diagnostic criteria are met:
- [criterion 1]
- [criterion 2]
- [criterion 3]
- [criterion 4]
Symptoms
- Cervical intraepithelial neoplasia is usually asymptomatic.
- Symptoms of cervical intraepithelial neoplasia may include the following:
- Abdominal pain
- Vaginal discomfort
- Dyspareunia
- Dysmenorrhea
- Frequent urination
Physical Examination
- Patients with cervical intraepithelial neoplasia usually are well-appearing.
- Physical examination shows no remarkable findings.
Laboratory Findings
- Laboratory findings associated with cervical intraepithelial neoplasia, include:
- HPV DNA Testing
Imaging Findings
- There are no imaging findings associated with cervical intraepithelial neoplasia.
Other Diagnostic Studies
- The most important diagnostic study for cervical intraepithelial neoplasia is vaginal colposcopy.
- Findings on vaginal colposcopy, include:
Treatment
Medical Therapy
- There is no medical treatment for cervical intraepithelial neoplasia; the mainstay of therapy is supportive care.
Surgery
- Surgery is the mainstay of therapy for cervical intraepithelial neoplasia.
- [Surgical procedure] in conjunction with [chemotherapy/radiation] is the most common approach to the treatment of cervical intraepithelial neoplasia.
- [Surgical procedure] can only be performed for patients with [disease stage] cervical intraepithelial neoplasia.
Prevention
- The most effective measure for the primary prevention of cervical intraepithelial neoplasia is the vaccination against oncogenic human papillomavirus (HPV) infection.
- Once diagnosed and successfully treated, patients with cervical intraepithelial neoplasia are followed-up every
- Follow-up testing includes [test 1], [test 2], and [test 3].
References
- ↑ Kumar, Vinay; Abbas, Abul K.; Fausto, Nelson; & Mitchell, Richard N. (2007). Robbins Basic Pathology (8th ed.). Saunders Elsevier. pp. 718–721. ISBN 978-1-4160-2973-1.
- ↑ 2.0 2.1 2.2 Georgios Nikolaou Papanikolaou Wikipedia. https://en.wikipedia.org/wiki/Georgios_Papanikolaou Accessed on March 29, 2016
- ↑ 3.0 3.1 Arends MJ, Buckley CH, Wells M (1998). "Aetiology, pathogenesis, and pathology of cervical neoplasia". J. Clin. Pathol. 51 (2): 96–103. PMC 500501. PMID 9602680.
- ↑ Herfs M, Crum CP (2013). "Laboratory management of cervical intraepithelial neoplasia: proposing a new paradigm". Adv Anat Pathol. 20 (2): 86–94. doi:10.1097/PAP.0b013e3182862aab. PMID 23399794.
- ↑ Dunne EF, Unger ER, Sternberg M, McQuillan G, Swan DC, Patel SS, Markowitz LE (2007). "Prevalence of HPV infection among females in the United States". JAMA. 297 (8): 813–9. doi:10.1001/jama.297.8.813. PMID 17327523.