Cervical intraepithelial neoplasia

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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

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 the squamous-columnar junction, which is also known as the "transformation zone".
The "transformation zone" is where the squamous epithelium of the ectocervix joins the columnar epithelium of the endocervix.
The presence of human papillomavirus (HPV) 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).
The viral replication of human papillomavirus (HPV) encodes proteins E6 and E7 which interfere with the normal epithelial cell functions. This leads to a deficient cell replication and excessive cell growth.
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
CIN I Cervical intraepithelial neoplasia I	Low-grade lesion squamous intraepithelial lesion (LGSIL)	Mild dysplasia, or abnormal cell growth Presence of koilocyte Typical cellular changes in the lower third of the epithelium
CIN II Cervical intraepithelial neoplasia II	High-grade lesion squamous intraepithelial lesion (HGSIL)	Moderate dysplasia Basal two-thirds of the epithelium Preservation of epithelial maturation
CIN III Cervical intraepithelial neoplasia III	High-grade lesion squamous intraepithelial lesion (HGSIL)	Severe atypical cellular changes Greater than two-thirds of the epithelial thickness Carcinoma in situ.

Causes

cervical intraepithelial neoplasia may be caused by either [cause1], [cause2], or [cause3].
cervical intraepithelial neoplasia is caused by a mutation in the [gene1], [gene2], or [gene3] gene[s].
There are no established causes for cervical intraepithelial neoplasia.

Differentiating cervical intraepithelial neoplasia from other Diseases

cervical intraepithelial neoplasia must be differentiated from other diseases that cause [clinical feature 1], [clinical feature 2], and [clinical feature 3], such as:

[Differential dx1]
[Differential dx2]
[Differential dx3]

Epidemiology and Demographics

The prevalence of cervical intraepithelial neoplasia is approximately [number or range] per 100,000 individuals worldwide.
In [year], the incidence of cervical intraepithelial neoplasia was estimated to be [number or range] cases per 100,000 individuals in [location].

Age

Patients of all age groups may develop cervical intraepithelial neoplasia.

cervical intraepithelial neoplasia is more commonly observed among patients aged [age range] years old.
cervical intraepithelial neoplasia is more commonly observed among [elderly patients/young patients/children].

Gender

cervical intraepithelial neoplasia affects men and women equally.

[Gender 1] are more commonly affected with cervical intraepithelial neoplasia than [gender 2].
The [gender 1] to [Gender 2] ratio is approximately [number > 1] to 1.

Race

There is no racial predilection for cervical intraepithelial neoplasia.

cervical intraepithelial neoplasia usually affects individuals of the [race 1] race.
[Race 2] individuals are less likely to develop cervical intraepithelial neoplasia.

Risk Factors

Common risk factors in the development of cervical intraepithelial neoplasia are [risk factor 1], [risk factor 2], [risk factor 3], and [risk factor 4].

Natural History, Complications and Prognosis

The majority of patients with cervical intraepithelial neoplasia remain asymptomatic for [duration/years].
Early clinical features include [manifestation 1], [manifestation 2], and [manifestation 3].
If left untreated, [#%] of patients with cervical intraepithelial neoplasia may progress to develop [manifestation 1], [manifestation 2], and [manifestation 3].
Common complications of cervical intraepithelial neoplasia include [complication 1], [complication 2], and [complication 3].
Prognosis is generally [excellent/good/poor], and the [1/5/10year mortality/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:

[symptom 1]
[symptom 2]
[symptom 3]
[symptom 4]
[symptom 5]
[symptom 6]

Physical Examination

Patients with cervical intraepithelial neoplasia usually appear [general appearance].
Physical examination may be remarkable for:

[finding 1]
[finding 2]
[finding 3]
[finding 4]
[finding 5]
[finding 6]

Laboratory Findings

There are no specific laboratory findings associated with cervical intraepithelial neoplasia.

A [positive/negative] [test name] is diagnostic of cervical intraepithelial neoplasia.
An [elevated/reduced] concentration of [serum/blood/urinary/CSF/other] [lab test] is diagnostic of cervical intraepithelial neoplasia.
Other laboratory findings consistent with the diagnosis of cervical intraepithelial neoplasia include [abnormal test 1], [abnormal test 2], and [abnormal test 3].

Imaging Findings

There are no [imaging study] findings associated with cervical intraepithelial neoplasia.

[Imaging study 1] is the imaging modality of choice for cervical intraepithelial neoplasia.
On [imaging study 1], cervical intraepithelial neoplasia is characterized by [finding 1], [finding 2], and [finding 3].
[Imaging study 2] may demonstrate [finding 1], [finding 2], and [finding 3].

Other Diagnostic Studies

cervical intraepithelial neoplasia may also be diagnosed using [diagnostic study name].
Findings on [diagnostic study name] include [finding 1], [finding 2], and [finding 3].

Treatment

Medical Therapy

There is no treatment for cervical intraepithelial neoplasia; the mainstay of therapy is supportive care.

The mainstay of therapy for cervical intraepithelial neoplasia is [medical therapy 1] and [medical therapy 2].
[Medical therapy 1] acts by [mechanism of action1].
Response to [medical therapy 1] can be monitored with [test/physical finding/imaging] every [frequency/duration].

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

There are no primary preventive measures available for cervical intraepithelial neoplasia.

Effective measures for the primary prevention of cervical intraepithelial neoplasia include [measure1], [measure2], and [measure3].

Once diagnosed and successfully treated, patients with cervical intraepithelial neoplasia are followed-up every [duration]. 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.

[Robbins-1] 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.

[wiki-2] 2.0 ^2.1 ^2.2 Georgios Nikolaou Papanikolaou Wikipedia. https://en.wikipedia.org/wiki/Georgios_Papanikolaou Accessed on March 29, 2016

[pmid9602680-3] 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.

[pmid23399794-4] 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.

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