Cervical intraepithelial neoplasia (CIN)

Ans. is d i.e. 5%

Rate of progression of CIN :

Ans. is c i.e. Colposcopy directed biopsy

Now this is a tricky question. Most of us at first instant think of cone biopsy as the answer, as cone biopsy would be both diagnostic as well as therapeutic. But if you go through various texts carefully it has been clearly mentioned that a female who has either frankly malignant or higher grades of CIN on pap smear should undergo Colposcopic directed biopsy and Endocervical curettage to confirm the diagnosis and see the extent of lesion as Pap smear is only a screening test and not diagnostic.

Post coital bleeding / irregular bleeding/Abnormal cervical cytology smear

abnormal do colposcopy Immediate colposcopy

“Women with high grade CIN or frankly malignant PAP smear should have colposcopic directed biopsy.” Harrison 17/e, p 608 Management of Abnormal cervical cytology smear / Irregular bleeding / Post coital bleeding :

* ASUS – Atypical squamous cells of unknown significance.

Thus from above chart it is clear

• In all visible lesions – Punch biopsy should be done
• In case of invisible lesion.

• For screening       Pap smear is recommended.

  For diagnosis       Colposcopic directed biopsy is the gold standard.

Cone biopsy is indicated only :

1. If limit of the lesion cannot be visualised with colposcopy.°
2. The squamo-columnar junction is not seen at colposcopy.°
3. Endocervical curettage shows histological findings positive for CIN-II CIN-III.°
4. Microinvasive carcinoma or adenocarcinoma in situ is suspected based on biopsy. colposcopy or cytology results.°
5. Lack of correlation between cytology biopsy and colposcopy results.°

Ans. is a i.e. Hysterectomy

Before discussing the answer to this questions lets first have a look at the treatment modalities available in case of CIN

Modalities for management of CIN

Ablative procedures

• Cryotherapy                                  • Loop electro surgical      • Hysterectomy
• Laser Vaporisation Therapy            excision (LEEP)                     • Conisation

Ablative Procedures :

• They are performed in out patient setting (OPD procedures).
• They must only be performed when the following conditions exist :

1. There is no evidence of micro invasion or invasive cancer (on cytology, colposcopy or ECC).
2. The lesion is located on the ectocervix (as determined by colposcopy and ECC).
3. There is no involvement of the endocervix (as determined by colposcopy and ECC).

Cytology and histology correspond with each other

Modalities available in Ablative procedure :

Cryotherapy

• It destroys the surface epithelium of the cervix by crystallizing the intra cellular water, resulting in eventual destruction of the cell.
• Major advantage is its ability to control exactly the depth and width of destruction by

• It is useful when :                                                                     It is particularly useful in :

–    Small lesions                                                                             – Larger lesions that cryoprobe cannot cover

–    CIN Grade I & II                                                                        – Irregular cervix with a Fish Mouth appearance.

–    When lesion is located in ectocervix                                            – Extension of the disease to vagina or satellite lesions on Vagina

• Lesions with extensive glandular involvement
• Depth of destruction = 4-5 mm                                     • Depth of destruction = 7mm
• Complications : – Discharge (M/C)                                 • Complications : – Slight discharge

Bleeding (Rare)                                                                   – Pain

–  Cervical Stenosis (Rare)                                                    – Bleeding

–  Infection (Rare)

drawback of Ablative procedures : it destroys the tissue and so no tissue specimen is available for additional histological evaluation.°

Excici‘In^I Procedures :They can be used

LEEP (Loop electrosurgical excision                         Cold Knife Conization procedure) or LLETZ= (Large loop

excision of transformation zone)

• It is both diagnostic as well as

therapeutic.

• It is an OPD procedure & requires LA.
• Now it has become the procedure of
• choice for treating CIN II & CIN III.

• Complications are less & include :

–    Slight bleeding

–    Infection

• It is both diagnosis and therapeutic (Indications-given earlier)
• It is performed in 0.T and requires GA
• It refers to the excision of a cone shaped part of cervix using a scalpel.
• Complications are more :

–    Pain°

–    Bleeding°

–    Infection°

when Endocervix is involved as well

Disadvantages of Excisional procedures :

All Excisional procedures produce – Pregnancy complication.

• Cervical stenosis°
• Incompetent os°
• Abortion°
• Premature labour°
  • Dystocia° Advantage of excision procedures over ablative methods is tissue is available after excision method for further histological studies and Transformation zone is visible.

Remember : In both ablative and excision methods patient should be followed with Pap smears every 3-4 months and by endocervical curettage (ECC), if endocervix is involved.

As far as hysterectomy is concerned :

“Hysterectomy is unacceptable as primary therapy for C1N1,2 or 3. However it may be considered when treating recurrent high grade cervical disease if childbearing has been completed or when a repeat cervical exicison is strongly indicated but technically not feasible.”

But most of the other books say that :

Large Loop excision of transformation zone has become the procedure of choice for management of CIN in many developed countries. But in developing countries where women are likely to default from follow up, hysterectomy is still the best option.

According to Shaw 14/e, p 365 ‑

Hysterectomy is desirable in : • Older and parous women

• When a woman cannot comply with follow-up
• If uterus is associated with fibroids, DUB or prolapse.
• If micro invasion exists.
• If recurrence occurs following conservative therapy.

According to Jeffocate 7/e, p 421 ‑

“If smear remains or becomes positive after conservative surgery, total hysterectomy is indicated, but the ovaries need not be removed if the woman is premenopausal. There is also a place for totarhysterectomy as an elective procedure when micro-invasion is found on biopsy, or when the patient is more than 40 years of age.”

Indications of Hysterectomy in CIN according to are :

• Microinvasion.
• CIN III at limits of conization specimen in selected patients.
• Poor compliance with follow up.

Other gynaecologic problems requiring hysterectomy such as fibroids, prolapse, endometriosis and PID.

Total abdominal hysterectomy

10

Conisation

Ans. is C. i.e. LEEP 

Although CIN can be treated with a variety of techniques, the preferred treatment for CIN 2 and 3 has become LEEP.

Though the patient is 35 yrs old and has completed her family, still hysterectomy won’t be the treatment of choice as-“Hysterectomy is currently considered too radical _.for treatment of CIN”­- (Novak’s Gynecology p.585)

Following are some situations in which hysterectomy remains a valid and appropriate method of treatment for CIN

1. Microinvasion
2. CIN 3 at limits of conization specimen in selected patients
3. Poor compliance with follow-up
4. Other gynecologic problems requiring hysterectomies, such as fibroids, prolapse, endometriosis, and pelvic inflammatory disease

Cervical intraepithelial neoplasia(CIN)

• Invasive squamous cell cervical cancers are preceded by a long phase of the preinvasive disease, collectively referred to as cervical intraepithelial neoplasia (CIN).
• Histopathologically a part of the full thickness of the cervical squamous epithelium is replaced by cells showing a varying degree of dysplasia, with the intact basement membrane.
• CIN may be suspected through a cytological examination using the Pap smear test or through colposcopic examination. Cervical cytology is the most efficacious and cost-effective method for cancer screening.
• The final diagnosis of CIN is established by the histopathological examination of a cervical punch biopsy or excision specimen.
• Additionally, human papillomavirus (HPV) testing can be performed to better triage women with early cytologic changes.

LSIL – Low grade squamous intraepithelial lesion

HSIL – High grade squamous intraepithelial lesion

CIS – Carcinoma in situ

*LSIL incorporates HPV changes (koilocytotic atypia) along with CIN I.

Role of HPV

• HPV infection is found in approx. 90% of cases of intraepithelial neoplasia. Type HPV18 is most commonly associated.
• HPV-18 is more specific than HPV-16 for invasive tumors.
• In most women, the HPV infection clears in 9 to 15 months. Only a minority of women exposed to HPV develop a persistent infection that may progress to CIN.
• Type-16 is the most common HPV type found in women with normal cytology.

Treatment

CIN 1

• Spontaneous regression of CIN 1 is seen in 60% to 85% of cases, typically within 2yrs.
• So patients who have biopsy diagnoses of C1N 1 are kept under observation with Pap testing performed at 6 and 12 months

Or

HPV DNA testing at 12 months

• After two negative test results or a single negative HPV DNA test, annual screening may be resumed.
• Women with persistent CIN 1 after 24 months should be treated with a local ablative method.

CIN 2 and 3

• CIN 2 & 3 carries a much higher probability of progressing to invasive cancer. All CIN 2 and 3 lesions require treatment.
• LEEP ( loop electrosurgical excision procedure) is the preferred treatment for CIN 2 and 3.
• Because all therapeutic modalities carry an inherent recurrence rate of up to 10%. cytologic follow-up at about 3-month intervals for 1 year is necessary.

Cryotherapy

• Considered acceptable therapy when the following criteria are met:

– Cervical intraepithelial neoplasia, grade 1 to 2

– Small lesion-Ectocervical location only.

– Negative endocervical sample

– No endocervical gland involvement on biopsy

Laser Ablation

• It has been used effectively for the treatment of CIN. But because of the expense of the equipment as well as the necessity for special training, laser ablation has fallen out of favor. The laser has been widely replaced by LEEP. Laser Excisional Conization
• Rather than using laser for vaporization leading to ablation, it can be used to excise a conization specimen. The ease of LEEP conization has significantly reduced the indications of laser conization.

Loop electrosurgical excision( LEEP)

• LEEP, variably known as simply loop excision or LLETZ (large loop excision of the transformation zone), is a valuable tool for the diagnosis and treatment of CIN.
• It uses low-voltage, high-frequency, thin wire loop electrodes to perform a targeted removal of a cervical lesion, an excision of the transformation zone, or cervical conization. This technique can be used in the outpatient setting.

Cold knife conization (scalpel)

• 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 CIN 2&3 in the following conditions:

– Limits of the lesion cannot be visualized with colposcopy.

– The squat-no-columnar junction (SCE) is not seen at colposcopy.

– Endocervical curettage (ECC) histologic findings are positive for CIN 2 or CIN 3.

– There is a substantial lack of correlation between cytology, biopsy, and colposcopy results. – Microinvasion is suspected based on biopsy, colposcopy, or cytology results. – The colposcopy is unable to rule out invasive cancer.

Ans. is C. i.e. LEEP

• The preferred initial treatment, however, is Loop Electrosurgical Excision Procedure (LEEP).
• LEEP has become the procedure of choice for the management of CIN II and CIN III’.
• This 35-year-old woman has completed her family (P3 + 0) and hence hysterectomy may be considered as the treatment of choice.
• But William’s gynecology states that ‘Hysterectomy’ is unacceptable as primary therapy for CIN I, II, or III.

• Loop electrosurgical excision procedure (LEEP), also known as large loop excision of the transformation zone (LLETZ), uses electric current to generate waveforms through a metal electrode that either cuts or coagulates cervical tissues.
• LEEP is frequently used for treating CIN II (Cervicalintraepithelial neoplasia) and CIN III because of its ease of use, low cost, and provision of additional tissue for histologic evaluation.
• LEEP uses a small, fine, wire loop attached to an electrosurgical generator to excise the tissue of interest. 
• Although CIN can be treated with a variety of techniques, the preferred treatment for CIN 2 and 3 has become LEEP.
• Though the patient is 35 yrs old and has completed her family, still hysterectomy won’t be the treatment of choice as-“Hysterectomy is currently considered too radical _.for treatment of CIN”­- (Novak’s Gynecology p.585)
• Following are some situations in which hysterectomy remains a valid and appropriate method of treatment for CIN

1. Microinvasion
2. CIN 3 at limits of conization specimen in selected patients
3. Poor compliance with follow-up
4. Other gynecologic problems requiring hysterectomies, such as fibroids, prolapse, endometriosis, and pelvic inflammatory disease

Cervical intraepithelial neoplasia(CIN)

• Invasive squamous cell cervical cancers are preceded by a long phase of the preinvasive disease, collectively referred to as cervical intraepithelial neoplasia (CIN).
• Histopathologically a part of the full thickness of the cervical squamous epithelium is replaced by cells showing a varying degree of dysplasia, with the intact basement membrane.
• CIN may be suspected through a cytological examination using the Pap smear test or through colposcopic examination. Cervical cytology is the most efficacious and cost-effective method for cancer screening.
• The final diagnosis of CIN is established by the histopathological examination of a cervical punch biopsy or excision specimen.
• Additionally, human papillomavirus (HPV) testing can be performed to better triage women with early cytologic changes.

Cryotherapy

• Considered acceptable therapy when the following criteria are met:

– Cervical intraepithelial neoplasia, grade 1 to 2

– Small lesion-Ectocervical location only.

– Negative endocervical sample

– No endocervical gland involvement on biopsy

Laser Ablation

• It has been used effectively for the treatment of CIN. But because of the expense of the equipment as well as the necessity for special training, laser ablation has fallen out of favor. The laser has been widely replaced by LEEP. Laser Excisional Conization
• Rather than using laser for vaporization leading to ablation, it can be used to excise a conization specimen. The ease of LEEP conization has significantly reduced the indications of laser conization.

Loop electrosurgical excision( LEEP)

• LEEP, variably known as simply loop excision or LLETZ (large loop excision of the transformation zone), is a valuable tool for the diagnosis and treatment of CIN.
• It uses low-voltage, high-frequency, thin wire loop electrodes to perform a targeted removal of a cervical lesion, an excision of the transformation zone, or cervical conization. This technique can be used in the outpatient setting.

Cold knife conization (scalpel)

• 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 CIN 2&3 in the following conditions:

– Limits of the lesion cannot be visualized with colposcopy.

– The squat-no-columnar junction (SCE) is not seen at colposcopy.

– Endocervical curettage (ECC) histologic findings are positive for CIN 2 or CIN 3.

– There is a substantial lack of correlation between cytology, biopsy, and colposcopy results. – Microinvasion is suspected based on biopsy, colposcopy, or cytology results. – The colposcopy is unable to rule out invasive cancer

The 5 most common techniques for the treatment of CIN include 2 ablative techniques—cryotherapy and laser ablation—and 3 excisional procedures—cold knife conization, laser cone excision, and LEEP.

That these techniques are of equal efficacy, averaging 80–90% success rates in the treatment of CIN. Cure depends on the size of the lesion, endocervical gland involvement, margin status of any excisional specimen, and endocervical curettage results.

Ans:C.)Stage III.

CERVICAL INTRAEPITHELIAL NEOPLASIA

• CIN I is characterized by dyplastic changes in the lower third of the squamous epithelium and koilocytotic change in the superficial layers of the epithelium.
• In CIN II, dysplasia extends to the middle third of the epithelium and takes the form of delayed keratinocyte maturation. It also is associated with some variation in cell and nuclear size, heterogeneity of nuclear chromatin, and presence of mitoses above the basal layer extending into the middle third of the epithelium. The superficial layer of cells shows some differentiation and occasionally demonstrates the koilocytotic changes .
• The next stage, CIN III, is marked by almost complete loss of maturation, even greater variation in cell and nuclear size, chromatin heterogeneity, disorderly orientation of the cells, and normal or abnormal mitoses; these changes affect virtually all layers of the epithelium

• Spectrum of cervical intraepithelial neoplasia (CIN), with normal squamous epithelium for comparison: CIN I with koilocytotic atypia; CIN II with progressive atypia in all layers of the epithelium; and CIN III (carcinoma in situ) with diffuse atypia and loss of maturation. 

• Cytologic features of cervical intraepithelial neoplasia (CIN) in a Papanicolaou smear. Superficial squamous cells may stain either red or blue. A, Normal exfoliated superficial squamous epithelial cells. B, CIN 1—low-grade squamous intraepithelial lesion (LSIL). C and D, CIN II and CIN III, respectively—both high-grade squamous intraepithelial lesions (HSILs). Note the reduction in cytoplasm and the increase in the nucleus-to-cytoplasm ratio as the grade of the lesion increases. This observation reflects the progressive loss of cellular differentiation on the surface of the cervical lesions from which these cells are exfoliated