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

Historical Perspective

• Cervical intraepithelial neoplasia was first discovered by Dr. Georgios Nikolaou Papanikolaou, a Greek pathologist, in 1927.
• In 1928, the first screening was developed by Aurel Babeș, a Romanian pathologist to diagnose cervical intraepithelial neoplasia.
• In 1980, human papillomavirus (HPV) was first identified in the pathogenesis of cervical intraepithelial neoplasia.

Classification

• Cervical intraepithelial neoplasia has 4 cytological classifications: Bethesda system, Papanicolaou classification, CIN nomenclature, and dysplasia nomenclature.
• Cervical intraepithelial neoplasia may be classified according to Papanicolau into 3 subtypes:

• CIN1 (Grade I)
• CIN2 (Grade II)
• CIN3 (Grade III)

• Cervical intraepithelial neoplasia may be classified according to Bethesda system into 3 subtypes:

• Low grade squamous intraepithelial lesion (LGSIL)
• High grade squamous intraepithelial lesions (HSIL)
• Carcinoma in situ

• Other variants of cervical intraepithelial neoplasia include [disease subtype 1], [disease subtype 2], and [disease subtype 3].

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.
• 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.

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].