Cervical intraepithelial neoplasia
Cervical intraepithelial neoplasia (CIN), also known as cervical dysplasia.
Refers to the abnormal growth of cells on the surface of the cervix that could potentially lead to cervical cancer.
CIN refers to the potentially precancerous transformation of cells of the cervix.
Between 250,000 and 1 million American women are diagnosed with CIN annually.
Women can develop CIN at any age.
Women generally develop CIN between the ages of 25 to 35.
It most commonly occurs at the squamocolumnar junction of the cervix: a transitional area between the squamous epithelium of the vagina and the columnar epithelium of the endocervix.
CIN is graded on a 1-3 scale, with 3 being the most abnormal.
Human papilloma virus (HPV) infection is necessary for the development of CIN.
CIN’s cause is a chronic infection of the cervix with HPV, especially infection with high-risk HPV types 16 or 18.
Many women with HPV infection never develop CIN or cervical cancer.
HPV resolves on its own, usually.
However, those with an HPV infection that lasts more than one or two years have a higher risk of developing a higher grade of CIN.
CIN is not a malignant process and can be cured.
Usually CIN remains stable or is eliminated by the immune system without need for intervention.
If left untreated in a small percentage of cases it will result in squamous cell cancer of the cervix.
CIN has no symptoms.
Cervical cancer symptoms include:
abnormal or post-menopausal bleeding
changes in bladder or bowel function
pelvic pain on examination
abnormal appearance or palpation of cervix.
High-risk HPV infections can inactivate tumor suppressor genes such as the p53 gene and the RB gene.
This inactivation of tumor suppressive genes allows the infected cells to grow and accumulate successive mutations, eventually leading to cancer.
Risks of developing CIN are increased in;
Infection with a high risk type of HPV, such as 16, 18, 31, or 33
Multiple sex partners
Lack of condom use
The earliest microscopic changes corresponding to CIN is epithelial dysplasia of the surface lining of the cervix and is undetectable by the woman.
The majority of dysplastic changes occur at the squamocolumnar junction, or transformation zone.
The transformation zone, an area of unstable cervical epithelium is prone to abnormal changes.
With HPV infection cellular changes such as koilocytes, are also commonly seen in CIN.
Most women with HPV infection do not develop high-grade intraepithelial lesions or cancer.
HPV is not alone enough to cause cervical cancer.
The Digene HPV test serves as a direct diagnosis and adjuvant to the Pap smear which is a screening device that allows for an examination of cells but not tissue structure, needed for diagnosis.
The diagnosis of CIN requires a biopsy for histological analysis.
Colposcopy with directed biopsy is the standard for disease detection.
The Bethesda System for Reporting Cervical/Vaginal Cytologic Diagnoses provides a uniform way to describe abnormal epithelial cells and determine specimen quality, thus providing clear guidance for clinical management.
Abnormalities arr classified as squamous or glandular and then further classified by the stage of dysplasia: atypical cells, mild, moderate, severe, and carcinoma.
CIN can start in any of the three stages and can either progress or regress.
The grade of squamous intraepithelial lesion can vary.
CIN is classified in grades:
CIN 1 (Grade I) Low-grade squamous intraepithelial lesion (LSIL)
Mild epithelial dysplasia is confined to the basal 1/3 of the epithelium and
typically corresponds to infection with HPV.
CINI has a high rate of regression back to normal cells.
It is usually managed expectantly.
The estimated annual incidence of CIN in the United States among persons who undergo screening is 4% for CIN 1 and 5% for CIN 2 and CIN 3.
CIN 2 (Grade II)
Moderate dysplasia confined to the basal 2/3 of the epithelium.
It represents a mix of low- and high-grade lesions not easily differentiated by histology
CIN 2+ encompasses CIN 2, CIN 3, adenocarcinoma in situ (AIS), and cancer.
CIN 3 (Grade III)
Severe dysplasia with undifferentiated neoplastic cells that span more than 2/3 of the epithelium
May involve the full thickness
May also be ref
CIN 3+ encompasses CIN 3, adenocarcinoma in situ, and cancer.
CIN 1 is ref
CIN 2 that is negative for p16, a marker for high-risk HPV, is ref
Those that are p16-positive are ref
CIN 3 is ref
CIN is usually discovered by the Pap smear.
The screening test Pap smears detects potentially precancerous changes through random sampling of the transformation zone of the cervix.
An abnormal Pap smear result may lead to [[colposcopy]] of the cervix.
With colposcopy the cervix is examined under magnification, and biopsy is taken of any abnormal appearing areas.
HPV screening happens either as a co-test with the Pap smear or can be done after a Pap smear showing abnormal cells, called reflex testing.
HPV Vaccine and Serotypes protected.
Gardasil – quadravalent 6, 11 (cause genital warts) 16, 18 (cause most cervical cancers) females and males age 9-26 3 before sexual debut or shortly thereafter
Cervarix – recombinant DNA vaccine (HPV4) 16, 18 females age 9-25 3
Gardasil 9 – bivalent vaccine (HPV2)6, 11, 16, 18, 31, 33, 45, 52, 58 (≈15% cervical cancer) females and males ages 9–26 3
These HPV vaccines do not protect against 100% of types of HPV known to cause cancer: screening is still recommended in vaccinated individuals.
Monitoring and treatment is the approach to secondary prevention of cervical cancer in cases of persons with CIN.
Treatment for CIN 1
Mild dysplasia, is not recommended if it lasts fewer than 2 years.
When a biopsy detects CIN 1 the woman has an HPV infection which may clear on its own within 12 months.
In young women closely monitoring CIN 2 lesions is reasonable.
Treatment for higher-grade CIN involves: removal/destruction of abnormal cervical cells by cryocautery, electrocautery, laser cautery, loop electrical excision procedure (LEEP), or cervical conization.
The lifetime recurrence rate of CIN is about 20%.
Surgical treatment of CIN lesions is associated with an increased risk of infertility.
Treatment of CIN during pregnancy increases the risk of premature birth.
Most CINs spontaneously regress.
Left untreated, about 70% of CIN 1 will regress within one year and 90% will regress within two years.
About 50% of CIN 2 will regress within 2 years without treatment.
The progression to cervical carcinoma in situ (CIS) occurs in approximately 11% of CIN 1 and 22% of CIN 2 cases.
Progression to invasive cancer occurs in approximately 1% of CIN 1, 5% in CIN 2 and at least 12% in CIN 3 cases.
Progression of cervical cancer typically takes 15 years with a range of 3 to 40 years.
A high-grade intraepithelial neoplasia can occur without first existing as a lower grade.
Treatment does not affect the chances of getting pregnant but it is associated with an increased risk of miscarriage in the second trimester.
Treatment is excisional or ablative procedures that remove or destroy cervical tissue with an efficacy rate of 90%.
Surgical procedures remove dysplastic tissue but leave normal appearing HPV infected tissues.