This document discusses benign cervical lesions including cervical ectopy and cervical intraepithelial neoplasia (CIN). It defines cervical ectopy as the replacement of squamous epithelium by columnar epithelium on the ectocervix. CIN is classified into three grades by the WHO based on the thickness of undifferentiated cells. Risk factors for CIN include HPV infection, early sexual activity, and smoking. Diagnosis involves cytology, colposcopy, and biopsy. Treatment options range from observation to ablative therapies to excision depending on the grade of CIN.

1. Benign Lesions of the Cervix
Dr. Aeysha Begum
MBBS, FCPS, MCPS
Assistant Professor
Department of Obstetrics & Gynaecology
Khwaja Yunus Ali Medical College

2. CERVICAL ECTOPY (EROSION)
Definition
• Cervical ectopy is a condition where the squamous epithelium of the
ectocervix is replaced by columnar epithelium, which is continuous
with the endocervix.

3. Etiology
• Congenital
• Acquired

4. Congenital
• At birth, in about one-third of cases, the columnar epithelium of the
endocervix extends beyond the external os.
• This condition persists only for a few days until the level of estrogen
derived from the mother falls.

5. Acquired
• Hormonal: The squamocolumnar junction is not static and its movement,
either inwards or outwards is dependent on estrogen.
When the estrogen level is high, it moves out so that the
columnar epithelium extends onto the vaginal portion of the cervix
replacing the squamous epithelium. This state is observed during pregnancy
and amongst ‘pill users’. The squamocolumnar junction returns back to its
normal position after 3 months following delivery and little earlier following
withdrawal of ‘pill’.
• Infection: The role of infection as the primary cause of ectopy has been
discarded. However, chronic cervicitis may be associated or else the
infection may supervene on an ectopy because of the delicate columnar
epithelium which is more vulnerable to trauma and infection.

6. • Pathogenesis
In the active phase of ectopy, the squamocolumnar junction moves out
from the os.
The columnar epithelium of the endocervix maintains its continuity
while covering the ectocervix replacing the squamous epithelium.
The replaced epithelium is usually arranged in a single layer (flat type)
or may be so hyperplastic as to fold inwards to accommodate in the
increased area—a follicular ectopy.
At times, it becomes heaped up to fold inwards and outwards—a
papillary ectopy.

7. • Pathogenesis
Underneath the epithelium, there are evidences of round cell infiltration and
glandular proliferation. The features of infection are probably secondary
rather than primary.
The columnar epithelium is less resistant to infection than the squamous
epithelium.
(A) Polyp (B) Polyp with ectopy (C) Ectopy (D) Eversion
Common benign lesions in the cervix

8. Different types of ectopy

9. CORRELATION Of DYSPLASIA, CIN (WHO) AND BETHESDA SYSTEM

10. • During the process of healing, the squamocolumnar junction gradually
moves up towards the external os.
• The squamous epithelium grows beneath the columnar epithelium until
it reaches at or near to its original position at the external os.
• Alternatively, the replacement is probably by squamous metaplasia of
the columnar cells.
• The possibility of squamous metaplasia of the reserve cells is also likely.
• During the process, the squamous epithelium may obstruct the mouth
of the underlying glands (normally not present in ectocervix) → pent up
secretion → retention cyst → Nabothian follicle.
• Alternatively, the epithelium may burrow inside the gland lumina.
• This process of replacement by the squamous epithelium is called
epidermidization.

11. Clinical Features
Symptoms:
1. The lesion may be asymptomatic.
2. Vaginal discharge—The discharge may be excessively mucoid. It
may be mucopurulent, offensive and irritant in presence of
infection; may be even blood-stained due to premenstrual
congestion.
3. Contact bleeding especially during pregnancy and ‘pill use’ either
following coitus or defecation may be associated.
4. Associated cervicitis may produce backache, pelvic pain and at
times, infertility.

12. Clinical Features
Signs:
Internal examination reveals:
• Per speculum—There is a bright red area surrounding and extending
beyond the external os in the ectocervix.
• The outer edge is clearly demarcated. The lesion may be smooth or
having small papillary folds. It is neither tender nor bleeds to touch.
• On rubbing with a gauze piece, there may be multiple oozing spots
(sharp bleeding in isolated spots in carcinoma).
• The feel is soft and granular giving rise to a grating sensation.

13. Differentials
• Ectropion: In chronic cervicitis, there is marked thickening of the cervical
mucosa with underlying tissue edema. These thickened tissues tend to push
out through the external os along the direction of least resistance. The entity
is most marked where the cervix has already been lacerated. In such
conditions, the longitudinal muscle fibers are free to act unopposed. As a
result, the lips of the cervix curl upwards and outwards to expose the red
looking endocervix so as to be confused with ectopy. The lips of the cervix
are curled back to expose the endocervix. This may be apparent when the
lips of the cervix are stretched by the bivalve speculum.
• Early carcinoma: It is indurated, friable and usually ulcerated which bleeds to
touch. Confirmation is by biopsy.
• Primary lesion (chancre): The ulcer has a punchedout appearance.
• Tubercular ulcer: There is indurated ulcer with caseation at the base. Biopsy
confirms the diagnosis.

14. • Management
Guidelines: All cases should be subjected to cytological examination
from the cervical smear to exclude dysplasia or malignancy.
Symptomatic cases
• Detected during pregnancy and early puerperium, the treatment
should be withheld for at least 12 weeks postpartum. In pill users, the
‘pill’ should be stopped and barrier method is advised.
• Persistent ectopy with troublesome discharge should be treated
surgically by—(i) thermal cauterization, (ii) cryosurgery and (iii) laser
vaporization.
• All the methods employed are based on the principle of destruction
of the columnar epithelium to be followed by its healing by the
squamous epithelium.

15. Premalignant Lesions

16. CERVICAL INTRAEPITHELIAL NEOPLASIA (CIN)
• World Health Organization (WHO) classified the CIN into three
categories correlating with former gradings of dysplasia and CIS. The
grading is done according to the thickness occupied by the
undifferentiated cells.
• Bethesda system classified cytologic abnormalities of premalignant
lesions into three categories:
(a) atypical squamous cells (ASC),
(b) low grade squamous intraepithelial lesions (LSIL)
(c) high grade squamous intraepithelial lesion (HSIL)
• LSILs include CIN I and the changes of HPV (Koilocytic atypia).

17. Normal stratified squamous epithelium of the ectocervix on the left is progressed to
CIN/CIS on the right through various degress of dysplastic changes.

18. Pathogenesis of HPV infection

20. Continuum of changes from reserve cell
hyperplasia to carcinoma-in-situ through
severe hyperplasia, CIN and CIS.

21. • Squamocolumnar junction (SCJ) is the meeting point of columnar
epithelium, that lines the endocervical canal, with squamous epithelium
that lines the ectocervix.
• In presence of estrogen the vaginal epithelium accumulates glycogen.
The lactobacilli act on glycogen to produce the acid pH (lactic acid) of
vagina.
• The metaplasia extends from the original SCJ (now squamosquamous)
outside to the newly developed (physiologically active) SCJ (now
squamocolumnar) inside. This area is defined as transformation zone
(TZ).

22. PATHOGENESIS:
• The process of carcinogenesis starts at the ‘transformation zone’
(TZ).
• The zone is not static but in a dynamic state.
• Two mechanisms are involved in the process of replacement of
endocervical columnar epithelium by squamous epithelium.
♦ By squamous metaplasia of the subcolumnar reserve cells.
♦ Squamous epidermidization by ingrowth of the squamous
epithelium of the ectocervix under the columnar epithelium.

23. PATHOGENESIS:
• Initially, the squamous cells are immature but ultimately become
mature and indistinguishable to the adjacent squamous
epithelium.
• This metaplastic process is very active at the time of menarche and
during and after first pregnancy.
• These periods are of high estrogenic phase which lowers the
vaginal pH. The acid pH probably is an important trigger for the
metaplastic process. This metaplastic cells have got the
potentiality to undergo atypical transformation by trauma or
infection.

24. • (A) Before puberty, the ectocervix is covered with
squamous epithelium;
• (B) Hightened estrogenic activity exposes the
columnar epithelium onto the ectocervix;
• (C) Replacement of columnar epithelium by
squamous epithelium to form TZ. New
squamocolumnar juncti on is situated at or slightly
outside the external os during reproductive
period;
• (D) Indrawing of the squamocolumnar junction
and the TZ well into the cervical canal following
menopause
A B
C D

25. • The prolonged effect of carcinogens can produce continuous changes in the
immature cells which may lead to malignancy.
• Early age sexual activity and multiple sexual partners are the most consistent
risk factors.
• HPV infection is transmitted through sexual activity. Microtrauma (sexual
intercourse) causes viral entry to the epithelium (basal or parabasal cells) of the
transformation zone adjacent to the SCJ.
• HPV DNA positivity is strongly related with the number of sexual partners.
• Women with multiple partners have high HPV DNA positivity rate (60%)
compared to women with single partner (21%).
• The important factors in the genesis of cervical cancer are:
(i) Infection with high-risk HPV,
(ii) Multiple types of HPV,
(iii) Persistence of infection,
(iv) Age > 30 years,
(v) Smoking, and
(vi) Compromised host immunodefense.

27. • EPIDEMIOLOGY
• Prevalence: CIN is predominantly a disease of younger
women. The mean age for carcinoma-in-situ is about 30
years, about 15 years less than that of invasive carcinoma.
• CIN like invasive carcinoma is most often related to some risk
factors.
• Infectious agents: The causative agents appear to be
transmitted to the susceptible women during intercourse.
Two viruses are implicated as casual agents.

28. RISK FACTORS FOR CIN AND CERVICAL CANCER
• infection: HPV (16, 18, 31, 33), HIV, Chlamydia.
• early sexual intercourse (<16 years).
• sexually transmitted diseases.
• early age of first pregnancy.
• too many and too frequent births.
• low socioeconomic status.
• multiple sexual partners.
• immunosuppressed (HIV positive) individuals.
• Husband whose previous wife died of cervical malignancy.
• oral pill users.
• smoking habits.

29. HUMAN PAPILLOMA VIRUS (HPV)
• HPV is epitheliotropic and plays an important role in the development
of CIN.
• HPV infected cells (koilocytes) are characterized by enlarged cells with
perinuclear halos.
• The nucleus is large, irregular and hyperchromatic. Depending on their
oncogenic potential, HPV types are broadly grouped into two.
• More than 130 HPV types have been identified.
High oncogenic risk—Types 16, 18, 31, 33, 35, 45, 56.
Low oncogenic risk—Types 6, 11, 42, 43.

30. • Over 99.7 percent of patients with CIN and invasive cancer
are found to be positive with HPV DNA.
• HPV DNA detection in cervical tissues may be a screening
procedure as that of Pap smear.
• Polymerase chain reaction or southern blot or hybrid capture
(HC) technique is used for HPV DNA detection.

31. • Pathogenesis of HPV Infection: HPV is epitheliotropic.
• Cervical epithelium → Infection (Latent/Active with virus replication)
→ Oncogenic HPV DNA integration to human genome → up-
regulation of viral oncogenes → expression of E6 and E7 oncoproteins
→ Interference of tumor suppressor genes (p53 and Rb) → host cell
immortalization and HPV induced neoplastic transformation.
• Viral DNA activates host cell p53 proteins. Activated p53 causes cell
apoptosis (cell death) and thus stop the viral multiplication. But HPV
E6 and E7 oncoproteins cause proteolytic degradation of P53. This
causes host cell immortalization and viral multiplicaion.

32. DIAGNOSIS OF CIN
• Cytologic Screening
Exfoliative cytology : the gold standard for screening.
(i) Dyskaryotic cells
(ii) Carcinoma-in-situ
• HPV-DNA testing is useful in cervical screening
• Visual inspection with acetic acid (VIA)
• Colposcopy

33. • Satisfactory colposcopic examination includes visualization of the
original SCJ, columnar epithelium, and the transformation zone in
entirety.
• Indications
1. Those having abnormal cytology.
2. Those with grossly abnormal cervical lesions even if cytology is
negative.
3. Those with post coital bleeding even if the smear is negative.

34. Abnormal colposcopic findings
• White epithelium — leukoplakia.
• Aceto white epithelium—epithelium turning white following application
of 5 percent acetic acid due to cell protein coagulation.
• Punctuation—dilated capillaries which appear on the surface as dots
(end on view of vessels).
• Mosaic—capillaries encircling polygonal shaped blocks of epithelial cells.
• Atypical blood vessels with irregular diameter and branching are
suggestive of invasive carcinoma.
• Irregular surface contour with ulceration and friability.

35. • Cervicography:
Photographs are taken from the cervix. Film is viewed by an expert
colposcopist.
Similar to colposcopy, cervix is treated with 5% acetic acid before
photography. It is complementary to cytology and colposcopy.

36. HISTOLOGIC PICTURE OF CIS
• The entire epithelial layer is affected.
• There is loss of stratification and polarity.
• The cells vary in size and shape.
• The nuclei stain deeply with presence of frequent mitosis and
abnormal chromatin pattern.
• The nuclei are larger and hyperchromatic with scanty
cytoplasm.
• The basement membrane remains intact.

37. TREATMENT OF CIN
• Preventive
• Definitive

38. PREVENTIVE
HPV vaccines:
• Bivalent vaccines (cervarix) against HPV types 16, 18 and quadrivalent (Gardasil)
against HPV types 16, 18, 6, 11 are effective in prevention of about 90% cervical
cancer.
• Both the vaccines have some cross protection aginst HPV types 31, 33 and 45.
• Vaccines are given to girls aged 12–18 years, in three doses IM over the deltoid
muscle.
• The impact of vaccines is greatest when it is given to females who have not been
already infected.
• This is the reason it is recommended to adolescent girls.
• Vaccines are safe and well tolerated.
• Immune defense is type specific and is effective only when given prophylactically.
• Vaccines are effective for at least 7.5 years.
• Screening with Pap test should be continued as the vaccines are type specific and
do not protect against the other types of HPV.

39. PREVENTIVE
▼ Other measures
• To delay sexual exposure until the cervical epithelium, especially in
the transformation zone, has attained physiological maturity.
• To maintain a local hygiene and to treat vaginal infections.
• To use condom specially during early sexual life.
• To maintain penile hygiene as it may be the reservoir for high risk
HPV.
• Reducing or quitting smoking reduces CIN.

40. DEFINITIVE TREATMENT
• The treatment modalities depend on:
1. Age of the patient.
2. Desire for reproduction.
3. Risk factors present.
4. Degree of dysplasia.
5. Facilities available for follow up such as colposcopy and/or cytology.

41. Treatment options
a. Observation with repeat smear and colposcopy every 4–6 months.
b. Local ablative methods
• Cryotherapy
• Cold coagulation
• Electrodiathermy
• Laser vaporization
c. Excisional methods
• Large loop (electrosurgical) excision of transformation zone
(LLETZ).
• Cone excision—using a knife or laser.
d. Hysterectomy—abdominal or vaginal.