Cervical intraepithelial neoplasia (CIN) refers to pre-cancerous changes that occur in the cells of the cervix. CIN is classified into three grades (CIN 1-3) based on how deep the abnormal cells are in the cervix. Human papillomavirus infection is the main cause of CIN. Screening through Pap tests and HPV testing can detect CIN early. Diagnosis involves colposcopy and biopsy of abnormal areas. Treatment options depend on the grade of CIN and include cryotherapy, loop electrosurgical excision, and conization. Leaving low-grade CIN untreated may allow spontaneous regression.

1. CERVICAL INTRAEPITHELIAL
LESION
PRESENTER: DR. HEM NATH SUBEDI
RESIDENT
OBGYN, COMS-TH , NEPAL

2. Contents
• Historical perspective
• Cervical anatomy
• Definition
• Classification
• Risk factors
• Epidemiology
• Etiology
• Screening
• Diagnosis
• Management

3. Cervical Anatomy
• The cervix is composed of
– Columnar epithelium: which lines the
endocervical canal
– Squamous epithelium: which covers the exocervix.
• The point at which they meet is called the
squamocolumnar junction (SCJ)

4. The Squamocolumnar Junction
• The SCJ rarely remains restricted to the external
os.
• Instead, it is a dynamic point that changes in
response to puberty, pregnancy, menopause, and
hormonal stimulation.
• In neonates, the SCJ is located on the exocervix.
• At menarche, the production of estrogen causes
the vaginal epithelium to fill with glycogen.
• Lactobacilli act on the glycogen to lower the pH,
stimulating the subcolumnar reserve cells to
undergo metaplasia .

12. Historical perspective
• The introduction of practical cytology by Papanicolau and
Traut in 1943.
• In 1956 Reagan and Hamonic introduced the term dysplasia
to designate these cervical epithelial abnormalities were
characeteristized by cytologic atypia , increased mitotic
activity and loss of polarity.
• Richart in 1976 proposed terminology of cervical
intraepithelial Neoplasia (CIN) which combined the
categories of severe dysplasia and carcinoma in situ in to
term CIN3.
• National Cancer institute in Bethesda ,maryland, the
Bethesda system was introduced and first publised in 1991
and subsequently updated and revised in 2001.

13. Definition
• Cervical dysplasia is a cytological term used to
describe cells resembling cancer cells.
• Cervical intraepithelial neoplasia (CIN) refers to
histopathological description in which a part or
full thickness of stratified squamous epithelium is
replaced by cells showing varying degrees of
dysplasia;however the basement membrane is
intact.

14. Classification
World Health Organization (WHO)
• In 1975 classified the CIN into three categories
correlating with former grading of dysplasia
and CIS.
• The grading is done according to the thickness
occupied by the undifferentiated cells.
– CIN 1: Mild dysplasia
– CIN 2: moderate dysplasia
– CIN 3: Severe dysplasia and carcinoma in situ

15. The 2001 Bethesda System (Abridged)
Epithelial Cell Abnormalities
Squamous cell
• Atypical squamous cells (ASC)
– Of undetermined significance (ASC-US)
– Cannot exclude high-grade squamous intraepithelial lesion
(HSIL) (ASC-H)
• Low-grade squamous intraepithelial lesion (LSIL)
– Encompassing human papillomavirus/mild dysplasia/ cervical
intraepithelial neoplasia (CIN) 1
• High-grade squamous intraepithelial lesion (HSIL)
– Encompassing moderate and severe dysplasia, carcinoma in situ,
CIN 2 and CIN 3
• Squamous cell carcinoma

16. Glandular cell
• Atypical glandular cells (AGC) (specify
endocervical, endometrial, or not otherwise
specified)
• Atypical glandular cells, favor neoplastic
(specify endocervical or not otherwise
specified)
• Endocervical adenocarcinoma in situ (AIS)
• Adenocarcinoma

19. Comparison of Cytology Classification
Systems
Bethesda system Dysplasia/CIN System Papinicolau System
With in normal limit Normal I
Infection (organism should be
specified)
Inflammatory Atypia
(Organism)
II
Reactive and non reactive
changes
Atypical squamous cell
1. Of undetermined
significance (ASC-US)
2. Exclude high grade lesions
(ASC-H)
Squamous atypia
HPV atypia, exclude LSIL
Exclude HSIL
HPV atypia
IIR
Low grade squamous
intraepithelial lesion (LSIL)
Mild dysplasia CIN 1
High Grade squamous
intraepithelial lesionn(HSIL)
Moderate dysplasia CIN 2
Severe dysplasia CIN 3
Carcinoma in situ
III
IV
Squamous cell carcinoma Squamous cell carcinoma V

20. Epidemiology
• Five lakhs new cases of cervical cancer are reported
annually.
• Incidence of cervical cancer in Nepal is 24.2 per
100,000.
• In India alone, 130,000 new cases occur with the death
toll of 70,000 cases every year.
• Cancer of the cervix accounts for 15% of all cancers in
women.
• Prevalence rate is 2.3 million annually globally.
• In India, it is 13–24 lakhs per year and 75% are in the
advanced stages.

21. Etiology
• Human Papiloma Virus (HPV) +Other
unidentified carcinogens.

22. Koilocytes
These cells are often seen in young women
suffering from HPV infection, and are cells
with perinuclear halo in the cytoplasm.
Koilocytes disappear as dysplasia advances.

24. Risk factors
• Average age 35–45 years. Pre-cancerous lesions occur 10–15
years earlier.
• Coitus before the age of 18 years.
• Multiple sexual partners.
• Delivery of the first baby before the age of 20 years.
• Multiparity with poor birth spacing between pregnancies.
• Poor personal hygiene.
• Carcinoma of the cervix shares similar epidemiological
features to those of sexually transmitted diseases and viral
infections and these are strongly linked to cancer cervix as
causative agents.
• Poor socioeconomic status.
• Women not attending screening program.
• Immunodeficiency status like HIV.

25. Pathophysiology

26. Screening
• Screening for cervical cancer differs from other
cancer screening because there is a well
defined premalignant stage of disease which
can be easily treated.
• Cervical screening was first introduced in
British Columbia and Finland.
• It is now one of the most successful cancer
prevention programmes.

27. Comparison for cervical screening
program
Guideline American cancer society ACOG
Initial screening Age 21 or 3 yrs after vaginal
sex
Age 21 or 3 yrs after vaginal
sex
Interval •Every year for conventional
•Every 2 yrs for liquid base
pap
•Every 2-3 y after age 30
with 3 consecutive normals
•Every year for either liquid
based Pap or conventional
•Every 2-3 y after age 30
with 3 consecutive normals
Discontinue Age 70 if 3 consecutive
normals in 10 yrs
No upper limit of age

28. Methods of screening
• Cytology
– Conventional method(Pap Smear),The conventional Pap
smear method had a sensitivity 51%, specificity 66.6%.
– Liquid based cytology (LBC) was developed to produce a
more representative sample of the specimen than a
conventional smear and to reduce contamination by
blood cells, mucus and pus.
– Studies have been reported showing a wide range of
sensitivities (44%-86%) and specificities (62%-98%).
• Sure path
• Thin prep.

29. Cervical cytology smear in CIN. This
cytology preparation shows a clump of
cervical epithelial cells demonstrating
moderate and severe dyskaryosis. (From
Figure 19.10. Alan Stevens, James Lowe and
Ian Scott: Core Pathology, 3rd Ed. Elsevier,
2009.)
Cervical squamous dysplasia, Pap smear
(From Figure 13-25. Edward C. Klatt:
Robbins and Cotran Atlas of Pathology,
2nd Ed. Saunders: Elsevier, 2010.)

31. Diagnosis
Colposcopy
• Acetowhite Epithelium
• Epithelium that turns white after application
of acetic acid (3%–5%) is called acetowhite
epithelium.
• The application of acetic acid coagulates the
proteins of the nucleus and cytoplasm and
makes the proteins opaque and white.

32. • Leukoplakia
• Translated literally, leukoplakia is white
plaque.
• In colposcopic terminology, this plaque is
white epithelium, visible before application of
acetic acid.
• Leukoplakia is caused by a layer of keratin on
the surface of the epithelium.

34. Punctation
• Dilated capillaries terminating on the surface
appear from the ends as a collection of dots
and are referred to as punctation.
• When these vessels occur in a well-
demarcated area of acetowhite epithelium,
they indicate an abnormal epithelium—most
often CIN.

37. • Mosaic
• Terminal capillaries surrounding roughly circular or
polygonal-shaped blocks of acetowhite epithelium
crowded together are called mosaic because their
appearance is similar to mosaic tile
• These vessels form a “basket” around the blocks of
abnormal epithelium.
• They may arise from a coalescence of many terminal
punctate vessels or from the vessels that surround the
cervical gland openings.
• Mosaicism tends to be associated with higher-grade
lesions and CIN 2.

40. • Atypical Vascular Pattern
• Atypical vascular patterns are characteristic of
invasive cervical cancer and include looped
vessels, branching vessels, and reticular
vessels.

41. Endocervical Curettage
• ASCCP guidelines do not require endocervical curettage. In
cases when an endocervical sample is needed, a cytobrush
is sufficient for sampling the endocervical canal.
Cervical Biopsy
• The cervical biopsy is performed at the area most likely to
have dysplasia. If the lesion is large or multifocal, multiple
biopsies may be necessary to ensure a complete sample of
the affected tissue.
• VIA
• SCHILLER’S TEST: VILI
• DIRECT BIOPSY

42. HPV testing
• DNA based assays like digene Hybrid capture
II,cervista HPV hr, cervista HPV 16/18 test,
Cobas 4800 HPV .

43. COURSES OF CIN

44. Management

50. Treatment

51. Treatment modalities
Cryotherapy
• Cryotherapy destroys the surface epithelium of the cervix by
crystallizing the intracellular water, resulting in the eventual
destruction of the cell.
• The temperature needed for effective destruction must be in the
range of (–20° to –30°C).
• Nitrous oxide (–89°C) and carbon dioxide (–65°C) produce
temperatures below this range and, therefore, are the most
commonly used gases for this procedure.
• Cryotherapy should be considered acceptable therapy when the
following criteria are met:
– CIN 1 that has persisted for 24 months, or CIN 2
– Small lesion
– Ectocervical location only
– Negative endocervical sample
– No endocervical gland involvement on biopsy PHOTO

52. Cryotherapy probes with various
size tips.

53. Laser Ablation
• Although rarely used in practice, laser ablation
was used effectively for the treatment of CIN.
• The expense of the equipment combined with
the necessity for special training limited the
use of laser ablation.
• Most early CIN is now managed expectantly,
so the need for ablation is decreasing.

55. Loop Electrosurgical Excision
• Loop excision should not be used before an
intraepithelial lesion is identified with histopathology.
• Although “see and treat” may be appropriate in
certain settings and among populations for whom
follow-up is not possible, the potential excision of the
entire transformation zone along with varying amounts
of the cervical canal, may compromise birth outcomes.
• This is particularly true for young women, who may
have large, immature transformation zones with
extensive acetowhite areas.

56. Electrodes (Utah Medical, Midvale, UT) used for a loop electroexcision procedure. The width of
the excised tissue specimens can range from 1.0 to 2.0 cm, and the specimen depth can be
adjusted by sliding the guard attached to the electrode shaft. Following excision, the base of the
cervix is often gently cauterized with a ball electrode.

57. Conization
• Conization is both a diagnostic and therapeutic procedure and has the
advantage over ablative therapies of providing tissue for further
evaluation to rule out invasive cancer
• Conization is indicated for diagnosis in women with HSIL or AGC
,adenocarcinoma in situ and may be considered under the following
conditions:
– Limits of the lesion cannot be visualized with colposcopy.
– The SCJ is not seen at colposcopy.
– Endocervical curettage (ECC) histologic findings are positive for CIN 2 or
CIN 3.
– Substantial lack of correlation between cytology, biopsy, and colposcopy
results.
– Microinvasion is suspected based on biopsy, colposcopy, or cytology
results.
– The colposcopist is unable to rule out invasive cancer.

59. Hysterectomy
• Hysterectomy is considered a treatment of last resort for
recurrent high-grade CIN.
• There are some situations in which hysterectomy remains a
valid and appropriate (although not mandatory) method of
treatment for CIN:
– Microinvasion
– CIN 3 at the endocervical limits of conization specimen in
selected patients
– Poor compliance with follow-up
– Other gynecologic problems requiring hysterectomy, such as
fibroids, prolapse, endometriosis, and pelvic inflammatory
disease
– Histologically confirmed recurrent high-grade CIN.

61. Prevention
• Use of condoms
• Dietary changes
• Behaviour changes
• Human Papilloma Virus Vaccine
• Because HPV infection is a necessary factor in the
development of cervical neoplasia, an important
step in primary prevention was the development
of a prophylactic vaccine to protect against HPV
infection.
– Bivalent vaccine
– Quadrivalent Vaccine
– Nonavalent vaccine

63. Refferences
• Francisco Garcia. Intraepithelial Disease of the Cervix, Vagina, and Vulva:
in Berek and Novaks Gynecology, 15th edition, wolter and Kluwer
.Newyork, pp 575.
• John A. rock. Precancerous lesions of Cervix: In Telindes textbook of
operative gynecology,10th edition, Wolter &Kluwer, Newyork,pp 1208-
1225.
• VG Padubidri Shirish N Daftary.Cervical Intraepithelial Neoplasia,
Carcinoma of Cervix: In Howkins & Bourne Shaw’s Textbook of
Gynaecology 16th edition, ELSEVIER , new delhi ,2011 pp485-490.
• Hiralal konor. premalignat lesions of cervix, vagina and vulva: In Dc
Dutta’s text book of gynecology, jp, new delhi.2014 pp..

64. • THE END