Cervical intraepithelial neoplasia (CIN) are premalignant lesions of the cervix caused by persistent HPV infection. CIN1 lesions often regress on their own while CIN2 and CIN3 lesions have a higher risk of progression to invasive cancer if left untreated. Diagnosis is made through cervical cytology, HPV testing, and colposcopy. Treatment options include ablative procedures like cryotherapy for low-grade lesions and excisional procedures like LEEP for high-grade lesions. Screening programs utilizing Pap smears or visual inspection techniques aim to detect and treat CIN early to prevent the development of invasive cervical cancer.

1. PREMALIGNANT
LESIONS OF THE
CERVIX
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2. ◦ Premalignant lesions of the cervix are called ‘cervical intra epithelial neoplasia’
(CIN)
Definition
It is the premalignant condition involving the uterine cervix, where the cellular
abnormalities are limited to the surface epithelium and do not extend beyond the
basement membrane.
And this is the long phase of preinvasive disease preceding invasive cervical
cancers

3. Terminology
◦ The older term was dysplasia, and depending on the cellular changes mild, moderate, severe
dysplasia and carcinoma in situ were the terms used
◦ Later studies demonstrated that all grades of dysplasias could progress to invasive cancer. Hence the
term Cervical intraepithelial neoplasia (CIN) was introduced
◦ CIN 3 grades
◦ CIN 1---mild dysplasia ---lower one third of epithelium involved
◦ CIN 2---moderate dysplasia---lower two third of the epithelium involved
◦ CIN 3 ---severe dysplasia and carcinoma in situ ---entire epithelium involved

5. ◦ CIN 1 lesions regresses on its own and progression to invasive cancer occurs
infrequently (1%)
◦ Hence it is also called as low-grade squamous intraepithelial lesion(LSIL)
◦ CIN 2 and 3 lesions, on the other hand, represent high-grade lesions, and are
caused by persistent HPV infection,
◦ not necessarily preceded by CIN 1,
◦ progression to invasive cancer occurs more often (13% and 30%)—-----high
grade squamous intra epithelial lesion(HSIL)

6. ◦ Diagnosis of CIN 2 is often not absolutely certain
◦ so recently , p16 immunostaining has been introduced to differentiate the CIN 2 lesions into
CIN 2 that is p16 positive is classified as HSIL
CIN 2 that is p16 negative is classified as LSIL
These classification is based on LAST (lower anogenital terminology standardisation project of HPV
associated lesions
During the transition from CIN to current terminology, the histology may be reported as LSIL (CIN
1), LSIL (CIN 2) if p16 negative, HSIL (CIN 2) if p16 positive and HSIL (CIN 3)

7. Prevalence
◦ Infection by high-risk HPV types occurs in 10–12% of women in India
◦ The prevalence is higher in younger women and decreases as age advances
◦ Prevalence of CIN 1 is about 3%, again higher in younger women
◦ . CIN 2 and 3 are found in 0.6% and 0.4% of population aged 30–65.

8. Aetiology and pathogenesis
◦ To understand the pathogenesis of preinvasive cervical lesions, an understanding of the
transformation zone (TZ) is essential
◦ The Transformation Zone
Most cervical malignancies occur in the region called the TZ
The ectocervix and the vagina are lined by squamous epithelium and the endocervix by columnar
epithelium
The junction between the two is known as the squamocolumnar junction (SCJ)
At birth, SCJ is located on the ectocervix in most females and this is called the original SCJ.

9. ◦ Under the influence of oestrogens at puberty and pregnancy, the endocervix everts to expose the
columnar epithelium
◦ Glycogenization of the columnar epithelium takes place, lactobacilli colonize the epithelium and
the pH becomes acidic
◦ These changes stimulate the columnar epithelium to undergo metaplasia and convert into
immature squamous and later mature squamous epithelium
◦ The junction between the metaplastic squamous epithelium and the columnar epithelium is
known as the new SCJ
◦ The area between the original SCJ and the new SCJ, which lies more cephalad, is the TZ

10. This is an area of high metaplastic activity and is vulnerable
to oncogenic effects of carcinogens and most cervical cancers
arise here
In postmenopausal women, the endocervical
canal becomes shorter and the new SCJ moves further
cephalad and lies within the endocervical canaL

11. Cervical carcinogenesis by HPV
◦ Occurs by 4 stages
◦ HPV infection: Infection by HPV occurs in >50% of women at some point in their life, the
peak prevalence being at 15–25 years.
◦ The majority of HPV infections are transient and clear within 6–12 months
◦ HPV persistence: Although millions of women may be infected with the virus, persistent
infection occurs only in a few

12. ◦ Progression to precancerous lesion: Progression occurs about 10 years after infection.
◦ The virus may also enter a latent phase and re-emerge years later.
◦ The virus may persist in the cytoplasm and give rise to low-grade lesions
◦ When the viral DNA integrates into host cell genome, high grade lesions develop.
◦ This is a critical event in the development of neoplasia
◦ . Local invasion: This leads to invasive cancer.

13. ◦Human papillomavirus
◦ Primary cause of cervical cancer (90% CIN ,vulvar and vaginal intraepithelial neoplasia)
◦ DNA virus OF PAPOVAVIRIDAE FAMILY
◦ HPV genome consist of circular, double stranded DNA which is small and enveloped with a 72 sided icosahedral
protein capsid
◦ The changes in the HPV infection are typically described as KOILOCYTOSIS
◦ Exclusively infect epithelial cells
◦ E6 and E7 are the primary HPV oncoprotiens that are directly involved in the cellular malignant transformation
◦ Sexually transmitted
◦ E6-Suppressing p53
◦ E7-Suppressing RB gene

14. ◦ More than 100 serotypes identified
Low-risk HPVs
◦ – Cause genital warts, condyloma accuminata and laryngeal papillomatus in new born
◦ – Seldom oncogenic
◦ – Predominantly HPV 6 and 11
◦ High-risk HPVs
◦ – Cause cervical, vaginal, vulvar cancer
◦ – Predominantly HPV 16 and 18
◦ – Also HPV 45, 56, 31, 33, 35, 58
◦ -HPV 31 and 33 causes CIN

15. Cofactors in pathogenesis of
intraepithelial and invasive cervical
cancer
◦ Early sexual activity
◦ Multiple sexual partners
◦ Partner with multiple sex partners
◦ Sexually transmitted infections
◦ – Herpes simplex
◦ – Gonorrhoea
◦ – Chlamydia

16. ◦ Immunosuppression
◦ – HIV infection
◦ – Autoimmune diseases
◦ – Hodgkin disease, leukaemia
◦ – Iatrogenic—Immunosuppressive drugs
◦ Smoking
◦ Combined OC pills
◦ HIV, human immunodeficiency virus
◦ MULTIPARITY
◦ Low socio economic status

17. prevention
◦ Primary prevention
◦ creating an awareness about the risk factors among women,
◦ promoting practice of safe sex
◦ use of condoms to prevent STDs
◦ lifestyle modification,
◦ screening for and early treatment of premalignant lesions
◦ HPV vaccines

18. ◦Secondary prevention
◦ prevention of progression of intraepithelial to invasive cancer.
◦ This consists of
◦ Screening
◦ appropriate management of preinvasive lesions
◦ and follow-up

19. HPV VACCINES
◦ Bivalent, quadrivalent and nanovalent vaccines have been developed to protect
against HPV infection, genital warts and cervical cancer
◦ Bivalent (16, 18) eg- cervarix , females, against cervical cancer
◦ Quadrivalent (6, 11, 16, 18) eg----Gardasil
◦ nanovalent (6, 11, 16, 18, 31, 33, 45, 52, 58) eg -----Gardasil 9
◦ Protection up to 10 years

20. ◦ Age of administration (girls and boys)
◦ – 9–13 years
◦ – Catch-up vaccination
◦ ƒFrom 14 to 26 years in girls
◦ ƒFrom 14 to 21 years for boys
◦ – Most effective if given before the onset of sexual activity
◦ Dosage
◦ – Three doses at 0, 2 and 6 months
◦ Screening with cytology must continue
◦ Recently WHO in April 2022 suggested use of
◦ Single dose of HPV vaccine (upto 21 years), target age 9-14 years

21. screening
◦ GOAL:-prevention of cervical cancer by detection, treatment, and follow up of preinvasive lesion
◦ METHODS USED FOR SCREENING include
◦ Cervical cytology
◦ HPV DNA testing
◦ Visual inspection with acetic acid (VIA)
◦ Visual inspection under lugols iodine

22. CERVICAL CYTOLOGY
Can be done by traditional pap smear or liquid based cytology
Pap smear
The abnormal cells of cervical neoplasia exfoliate and can be collected by scraping the cervix and
staining the smear
it is possible to diagnose the degree of intraepithelial or invasive neoplasia
This method of screening by cytology testing was introduced by Papanicolaou and is known as the
Pap smear or Pap test.

23. Technique
patient is placed in dorsal position and cusco speculum is
inserted
An ayre spatula is taken and its longer end fixed at the
external os
it is then rotated through 360 degree over the portio
vaginalis of cervix
it is then spread on a slide and before it dries ,is immersed
in equal parts of 95% ethyl alcohol and ether and kept for 2
hours to fix it

24. ◦ Then slide is air dried and then stained with Papanicolaou stain
◦ No vaginal examination should be performed prior to taking the smear
◦Limitation of pap smear
◦ There would be errors in sampling, preparation and interpretation leading to reduced sensitivity
of about 5O%

25. Liquid based preparation
◦ Here a liquid based medium can be used to collect the cytology sample and preserve the collected cells
◦ This will decrease errors in sampling and preparation thus increasing sensitivity to 80 % also same smear
can be used for DNA testing
◦ Technique
◦ Cell sample collected with an endo cervical brush and rinsed in a vial containing the liquid
preservative(methanol)
◦ Thus 80 to 90 percent of cells are transferred to the liquid media Thus sensitivity is increased
◦ Fixative with cells are further centrifuged and analysed

26. HPV DNA testing
◦ It has higher sensitivity and specificity compared to cervical cytology
◦ Can detect the high risk HPV types within hours
◦ It is more helpful in testing women older than 30 years
◦ HPV testing is a critical component of the triage for ASC-US(atypical squamous cells of
undetermined significance) cytology,
◦ as a compound of co testing with simultaneous cytology and a stand alone primary screening
method

27. VISUAL INSPECTION TECHNIQUE –VIA and
VILI
◦ Visual inspection with acetic acid and visual inspection with lugols iodine are alternative technique to cytology in
low resource settings
◦ Advantage
◦ Any health care individual can perform these test after formal training
◦ Cost effective
◦ Method of choice in India
◦ Technique
◦ VIA –After application of 3-5 % acetic acid, if the cervical epithelium contains an abnormal load of cellular
proteins, the acetic acid coagulate the proteins leading to an opaque white appearance
◦ And is considered--VIA positive

28. VILI
◦ Visual inspection of cervix with lugols iodine is generally performed after the VIA test
◦ LUGOLS iodine reacts with glycogen to form brown or black colouration
◦ Normal mature squamous epithelium contain glycogen
◦ When in contact with lugols iodine it turns black
◦ Precancerous lesion and cancerous lesion contain little or no amount of glycogen thus turning it
yellow after lugols iodine application—VILI positive

29. Bethesda system
◦ Developed in 1991 to create a uniform system
◦ In 2001 it was further modified
◦ The Bethesda system officially called The Bethesda System for Reporting Cervical Cytology, is a
system for reporting cervical or vaginal cytologic diagnoses, used for reporting Pap smear results
◦ The Bethesda system of reporting the cytology
◦ smears assures uniformity of reporting and provides clear guidelines for further evaluation and
management.

30. BETHESDA SYSTEM OF INTERPRETATION

32. Evaluation of an abnormal smear

33. COLPOSCOPY
◦ Colposcopy is the visualization of the cervix, vagina and vulva under magnification to
detect premalignant and malignant lesions
◦ Gold standard for the diagnosis
The colposcope is a magnification system with a light source, mounted on a stand
Limitation
Upper two third of endocervix not visualised

34. Steps of colposcopic examination
◦ Place the patient in dorsal/lithotomy position
◦ Place colposcope 1 feet from vulva
◦ Insert bivalve speculum
◦ Focus colposcope on the cervix
◦ Use low power for overall visualization initially

35. ◦ Shift to high power for closer visualization of lesions
◦ Clean with saline, remove mucus and note findings
◦ Apply 3% acetic acid and note findings
◦ Apply Lugol’s iodine and note findings
◦ Document colposcopic findings
◦ Perform guided biopsy, if indicated

36. ◦ Saline removes mucus and discharge and makes it possible to view obvious abnormalities.
◦ On application of acetic acid, areas of high chromatin density stain white (acetowhite areas;)
signifying the areas of squamous metaplasia, CIN and cancer

37. COLPOSCOPIC REPORTING
◦ NORMAL COLPOSCOPY
◦ LOW GRADE DISEASE (HPV/CIN 1)
◦ HIGH GRADE DISEASE (CIN 2 OR 3 )
◦ INVASIVE CANCER

38. COLPOSCOPIC FEATURES OF LOW GRADE
AND HIGH GRADE LESIONS
LOW GRADE LESIONS HIGH GRADE LESIONS
Thin acetowhite epithelium
Irregular geographic border
Fine mosaic
Punctuation
Dense acetowhite epithelium
Rapid appearance of aceto whitening
Complete mosaic
Coarse punctuation
Sharp border
Inner border sign and ridge sign

39. Management of CIN
◦ Based on risk of progression
◦ Low grade CIN can be kept under close observation with HPV testing ,cervical cytology and
colposcopy
◦ High grade CIN and patients not compliant for follow up are treated
◦ There are ablative and excisional methods

40. Ablative method Excisional methord
Cryotherapy
Laser ablation
Conisation
hysterectomy
LEEP(loop electro surgical excision)
LASER excision

41. cryotherapy
◦ This procedure destroys the surface epithelium of the cervix by crystalising the intracellular water
causing destruction of the cell
◦ Temp between -20 to -30
◦ Best method is the freeze thaw freeze method --in which an ice ball is achieved 5 mm beyond
the edge of the probe
◦ CIN 1 AND CIN 2 lesions can be treated with cryotherapy

42. ◦ Disadvantages
◦ Not suitable for lesion extending more than 25 % of the cervix and those
extending to the endocervical canal and vaginal fornices
◦ Patient experience a watery malodourous blood stained discharge post procedure
◦ And should advice to avoid coitus for a month
◦ not suitable for treating CIN 3

43. Laser ablation
◦ Same indications as cryotherapy
◦ Disadvantage is that of expense of the equipment and the need for special training
◦ Hence not used now as CIN1 can be easily treated with cryotherapy
◦ And high grade lesion are managed by LEEP (loop electro surgical excision )

44. LEEP(loop electrosurgical excision)
◦ Diagnostic and therapeutic
◦ Procedure of choice in CIN 2 AND CIN 3 where colposcopy is unsatisfactory
◦ Most commonly used method of treatment (95% cure rate)
◦Advantages
◦ Simple and safe op procedure under local anesthesia
◦ Low cost equipment
◦ Easy to learn
◦ Specimen obtained for histopathology
◦ No chance of missing an invasive cancer
◦ Loop of various size available to fit the lesion

45. ◦ Here electric current is used for a large loop excision of the transformation zone
◦ Can be done under colposcopic control
◦ Usually specimen is removed in a single pass, but larger lesion may need multiple passes
◦ For ectocervical lesions loop of 15 -20 mm are used while endocervical samples are obtained with
10 mm loop
◦ For lesion extending into the endocervical canal, the endocervical lesion is excised after the
ectocervical excision

46. Follow up
◦ Patient advised to avoid vaginal douches,tampons and coitus for 1 month
◦ All patients followed up at one year with colposcopy
◦ If there is a persistent lesion biopsy is necessary and a repeat LEEP can be performed
◦ Cytological screening should continue. if the margins are positive, a repeat procedure may be
continued

47. complications
◦ Intra and post operative haemorrhage
◦ Cervical stenosis
◦ Increased preterm delivery and pprom(after deep excision )

48. Conisation or cone biopsy
◦ Before colposcopy conisation was the standard method of evaluating an abnormal smear
◦ INDICATIONS
◦ Unsatisfactory colposcopy or inability to see the lesion entirely
◦ Positive endocervical curettage
◦ Glandular lesions
◦ To diagnose microinvasive carcinoma
◦ Persistant or recurrent CIN after LEEP or ablation

49. procedure
◦ Can be performed with cold knife , electro surgical wire or LASER
◦ The entire transformation zone including the cervical lesion is removed under general or regional
anesthesia
◦ To reduce the blood loss cervix injected with vasoconstrictive agent ,this will cause blanching of
the cervix
◦ Cervix then stained with lugols iodine to outline the lesion
◦ A scalpel is then used to take the cone In a cold knife cone

50. ◦ Cone should be symmetrical around the endocervical canal with the apex in the canal but below
the internal os
◦ Endocervical curettage is performed above the apex of the cone to screen for residual disease
◦ After conisation the margins of the cone must be free of CIN
◦ ,In such cases conisation is adequate
◦ If margins are involved hysterectomy is best

51. Complications
◦ Secondary haemorrhage
◦ Cervical stenosis and haematometra
◦ Future infertility
◦ Cervical incompetence and preterm labour

52. Hysterectomy
◦ Not usually considered as a method of treatment for CIN as it is too radical
◦ Indications
◦ Microinvasive carcinoma
◦ CIN 3 at the limits of the conisation specimen
◦ Poor compliance with follow up
◦ Associated fibroids needing hysterectomy

53. Thank you