Cervical intraepithelial neoplasia
Encyclopedia
Cervical intraepithelial neoplasia (CIN), also known as cervical dysplasia and cervical interstitial neoplasia, is the potentially premalignant transformation and abnormal growth (dysplasia
) of squamous cells on the surface of the cervix
. CIN is not cancer, and is usually curable. Most cases of CIN remain stable, or are eliminated by the host's immune system
without intervention. However a small percentage of cases progress to become cervical cancer
, usually cervical squamous cell carcinoma (SCC), if left untreated. The major cause of CIN is chronic infection
of the cervix with the sexually transmitted human papillomavirus
(HPV), especially the high-risk HPV types 16 or 18. Over 100 types of HPV have been identified. About a dozen of these types appear to cause cervical dysplasia and may lead to the development of cervical cancer. Other types cause wart
s.
The earliest microscopic change corresponding to CIN is dysplasia
of the epithelial
or surface lining of the cervix
, which is essentially undetectable by the woman. Cellular changes associated with HPV infection, such as koilocytes, are also commonly seen in CIN. CIN is usually discovered by a screening test, the Papanicolaou or "Pap" smear
. The purpose of this test is to detect potentially precancerous changes. Pap smear results may be reported using the Bethesda System
. An abnormal Pap smear
result may lead to a recommendation for colposcopy
of the cervix, during which the cervix is examined under magnification. A biopsy
is taken of any abnormal appearing areas. Cervical dysplasia can be diagnosed by biopsy.
CIN is classified in grades:
However most CIN spontaneously regress. Left untreated, about 70% of CIN-1 will regress within two years, and 90% within two years. About 50% of CIN 2 will regress within 2 years without treatment.
Progression to cancer typically takes 15 (3 to 40) years.
Also, evidence suggests that cancer can occur without first detectably progressing through these stages and that a high grade intraepithelial neoplasia can occur without first existing as a lower grade.
It is thought that the higher risk HPV infections, have the ability to inactivate tumor suppressor genes such as the p53
gene and the RB
gene, thus allowing the infected cells to grow unchecked and accumulate successive mutations, eventually leading to cancer.
, loop electrical excision procedure
(LEEP), or cervical conization
. Therapeutic vaccines
are also in development. The lifetime recurrence rate of CIN is about 20%, but it isn't clear what proportion of these cases are new infections rather than recurrences of the original infection.
A number of risk factors have been shown to increase a woman's likelihood of developing CIN, including poor diet
, poor personal hygiene, multiple sexual partners, lack of condom
use, and cigarette smoking
.
Using condoms increases regression of cervical dysplasia.
Dysplasia
Dysplasia , is a term used in pathology to refer to an abnormality of development. This generally consists of an expansion of immature cells, with a corresponding decrease in the number and location of mature cells. Dysplasia is often indicative of an early neoplastic process...
) of squamous cells on the surface of the cervix
Cervix
The cervix is the lower, narrow portion of the uterus where it joins with the top end of the vagina. It is cylindrical or conical in shape and protrudes through the upper anterior vaginal wall...
. CIN is not cancer, and is usually curable. Most cases of CIN remain stable, or are eliminated by the host's immune system
Immune system
An immune system is a system of biological structures and processes within an organism that protects against disease by identifying and killing pathogens and tumor cells. It detects a wide variety of agents, from viruses to parasitic worms, and needs to distinguish them from the organism's own...
without intervention. However a small percentage of cases progress to become cervical cancer
Cervical cancer
Cervical cancer is malignant neoplasm of the cervix uteri or cervical area. One of the most common symptoms is abnormal vaginal bleeding, but in some cases there may be no obvious symptoms until the cancer is in its advanced stages...
, usually cervical squamous cell carcinoma (SCC), if left untreated. The major cause of CIN is chronic infection
Infection
An infection is the colonization of a host organism by parasite species. Infecting parasites seek to use the host's resources to reproduce, often resulting in disease...
of the cervix with the sexually transmitted human papillomavirus
Human papillomavirus
Human papillomavirus is a member of the papillomavirus family of viruses that is capable of infecting humans. Like all papillomaviruses, HPVs establish productive infections only in keratinocytes of the skin or mucous membranes...
(HPV), especially the high-risk HPV types 16 or 18. Over 100 types of HPV have been identified. About a dozen of these types appear to cause cervical dysplasia and may lead to the development of cervical cancer. Other types cause wart
Wart
A wart is generally a small, rough growth, typically on a human’s hands or feet but often other locations, that can resemble a cauliflower or a solid blister. They are caused by a viral infection, specifically by human papillomavirus 2 and 7. There are as many as 10 varieties of warts, the most...
s.
The earliest microscopic change corresponding to CIN is dysplasia
Dysplasia
Dysplasia , is a term used in pathology to refer to an abnormality of development. This generally consists of an expansion of immature cells, with a corresponding decrease in the number and location of mature cells. Dysplasia is often indicative of an early neoplastic process...
of the epithelial
Epithelium
Epithelium is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. Epithelial tissues line the cavities and surfaces of structures throughout the body, and also form many glands. Functions of epithelial cells include secretion, selective...
or surface lining of the cervix
Cervix
The cervix is the lower, narrow portion of the uterus where it joins with the top end of the vagina. It is cylindrical or conical in shape and protrudes through the upper anterior vaginal wall...
, which is essentially undetectable by the woman. Cellular changes associated with HPV infection, such as koilocytes, are also commonly seen in CIN. CIN is usually discovered by a screening test, the Papanicolaou or "Pap" smear
Pap smear
The Papanicolaou test is a screening test used in to detect pre-cancerous and cancerous processes in the endocervical canal of the female reproductive system. Changes can be treated, thus preventing cervical cancer...
. The purpose of this test is to detect potentially precancerous changes. Pap smear results may be reported using the Bethesda System
Bethesda System
The Bethesda System is a system for reporting cervical or vaginal cytologic diagnoses, used for reporting Pap smear results. It was introduced in 1988, and revised in 1991 and 2001...
. An abnormal Pap smear
Pap smear
The Papanicolaou test is a screening test used in to detect pre-cancerous and cancerous processes in the endocervical canal of the female reproductive system. Changes can be treated, thus preventing cervical cancer...
result may lead to a recommendation for colposcopy
Colposcopy
Colposcopy is a medical diagnostic procedure to examine an illuminated, magnified view of the cervix and the tissues of the vagina and vulva. Many premalignant lesions and malignant lesions in these areas have discernible characteristics which can be detected through the examination...
of the cervix, during which the cervix is examined under magnification. A biopsy
Biopsy
A biopsy is a medical test involving sampling of cells or tissues for examination. It is the medical removal of tissue from a living subject to determine the presence or extent of a disease. The tissue is generally examined under a microscope by a pathologist, and can also be analyzed chemically...
is taken of any abnormal appearing areas. Cervical dysplasia can be diagnosed by biopsy.
Grades
Depending on several factors such as the type of HPV and the location of the infection, CIN can start in any of the three stage, and can either progress, or regress.CIN is classified in grades:
| Histology Grade | Corresponding Cytology | Description | Image |
|---|---|---|---|
| – | – | Normal cervical epithelium | |
| CIN 1 (Grade I) | LSIL | The least risky type, represents only mild dysplasia Dysplasia Dysplasia , is a term used in pathology to refer to an abnormality of development. This generally consists of an expansion of immature cells, with a corresponding decrease in the number and location of mature cells. Dysplasia is often indicative of an early neoplastic process... , or abnormal cell growth. It is confined to the basal 1/3 of the epithelium. This corresponds to infection with HPV, and typically will be cleared by immune response in a year or so, though can take several years to clear. |
|
| CIN 2/3 | HSIL | Formerly subdivided into CIN2 and CIN3. | |
| CIN 2 (Grade II) | Moderate dysplasia confined to the basal 2/3 of the epithelium | ||
| CIN 3 (Grade III) | Severe dysplasia that spans more than 2/3 of the epithelium, and may involve the full thickness. This lesion may sometimes also be referred to as cervical carcinoma in situ Carcinoma in situ Carcinoma in situ is an early form of cancer that is defined by the absence of invasion of tumor cells into the surrounding tissue, usually before penetration through the basement membrane. In other words, the neoplastic cells proliferate in their normal habitat, hence the name "in situ"... . |
Incidence
Between 250,000 and 1 million American women are diagnosed with CIN annually. Women can develop CIN at any age, however, women generally develop it between the ages of 25 to 35.Risk factors
Some risk factors that have been found to be important in developing CIN are:- Women who become infected by a "high risk" types of HPV, such as 16, 18, 31, or 45
- Women who have had multiple sexual partners
- Women who smoke
- Women who are immunodeficient
- Women who give birth before age 17
Progression and regression
It used to be thought that cases of CIN progressed through these stages toward cancer in a linear fashion.However most CIN spontaneously regress. Left untreated, about 70% of CIN-1 will regress within two years, and 90% within two years. About 50% of CIN 2 will regress within 2 years without treatment.
Progression to cancer typically takes 15 (3 to 40) years.
Also, evidence suggests that cancer can occur without first detectably progressing through these stages and that a high grade intraepithelial neoplasia can occur without first existing as a lower grade.
It is thought that the higher risk HPV infections, have the ability to inactivate tumor suppressor genes such as the p53
P53
p53 , is a tumor suppressor protein that in humans is encoded by the TP53 gene. p53 is crucial in multicellular organisms, where it regulates the cell cycle and, thus, functions as a tumor suppressor that is involved in preventing cancer...
gene and the RB
Retinoblastoma protein
The retinoblastoma protein is a tumor suppressor protein that is dysfunctional in the majority types of cancer. One highly studied function of pRb is to prevent excessive cell growth by inhibiting cell cycle progression until a cell is ready to divide...
gene, thus allowing the infected cells to grow unchecked and accumulate successive mutations, eventually leading to cancer.
Treatment
Treatment for higher grade CIN involves removal or destruction of the neoplastic cervical cells by cryocautery, electrocautery, laser cauteryCauterization
The medical practice or technique of cauterization is the burning of part of a body to remove or close off a part of it in a process called cautery, which destroys some tissue, in an attempt to mitigate damage, remove an undesired growth, or minimize other potential medical harmful possibilities...
, loop electrical excision procedure
Loop electrical excision procedure
The loop electrosurgical excision procedure is currently one of the most commonly used approaches to treat high grade cervical dysplasia discovered on colposcopic examination. In UK it is known as "large loop excision of the transformation zone" . The procedure has many advantages including low...
(LEEP), or cervical conization
Cervical conization
Cervical conization refers to a biopsy of the cervix in which a cone-shaped sample of tissue is removed from the mucous membrane. Conization may be used either for diagnostic purposes, or for therapeutic purposes to remove pre-cancerous cells.Types include:* cold knife conization...
. Therapeutic vaccines
HPV vaccine
The human papilloma virus vaccine prevents infection with certain species of human papillomavirus associated with the development of cervical cancer, genital warts, and some less common cancers...
are also in development. The lifetime recurrence rate of CIN is about 20%, but it isn't clear what proportion of these cases are new infections rather than recurrences of the original infection.
A number of risk factors have been shown to increase a woman's likelihood of developing CIN, including poor diet
Diet (nutrition)
In nutrition, diet is the sum of food consumed by a person or other organism. Dietary habits are the habitual decisions an individual or culture makes when choosing what foods to eat. With the word diet, it is often implied the use of specific intake of nutrition for health or weight-management...
, poor personal hygiene, multiple sexual partners, lack of condom
Condom
A condom is a barrier device most commonly used during sexual intercourse to reduce the probability of pregnancy and spreading sexually transmitted diseases . It is put on a man's erect penis and physically blocks ejaculated semen from entering the body of a sexual partner...
use, and cigarette smoking
Tobacco smoking
Tobacco smoking is the practice where tobacco is burned and the resulting smoke is inhaled. The practice may have begun as early as 5000–3000 BCE. Tobacco was introduced to Eurasia in the late 16th century where it followed common trade routes...
.
Using condoms increases regression of cervical dysplasia.