Cervical Intraepithelial Neoplasia

Cervical intraepithelial neoplasia (CIN) is the precancerous lesion of the squamous epithelium of the cervix. It is caused by persistent infection with high risk HPV (types 16 and 18 account for about 70 percent of cervical cancers; types 31, 33, 45, 52 and 58 also contribute). It arises mainly in the transformation zone.

Grading is by depth of epithelial involvement:

• CIN 1 (low grade squamous intraepithelial lesion): lower third. Usually an HPV effect, and regresses spontaneously in 60 to 90 percent.
• CIN 2: middle two thirds. Heterogeneous.
• CIN 3 (high grade squamous intraepithelial lesion): full thickness. Progression to invasive cancer occurs in 12 to 30 percent over 10 to 30 years if untreated.

Risk factors: early sexual debut, multiple partners, smoking, immunosuppression (HIV, transplant), long term combined oral contraceptive use, and absent screening.

Adenocarcinoma in situ is the glandular equivalent.

• Asymptomatic; diagnosed through screening.
• Abnormal bleeding (postcoital or intermenstrual) or discharge occasionally brings women to examination.
• Colposcopic appearance: acetowhite epithelium, mosaic, punctation and atypical vessels after 5 percent acetic acid, with iodine negative areas; higher grade lesions show dense acetowhite change, sharp borders, coarse punctation, coarse mosaic, cuffed gland openings and a ridge sign.
• Features suggesting invasion: irregular surface, atypical vessels, friability, necrosis and ulceration.

• Screening: cytology every 3 years from age 25 to 49 and every 5 years from 50 to 64, or primary high risk HPV testing every 5 years from age 30 (with cytology triage of HPV positive results). Women with HIV are screened annually.
• Referral for colposcopy: persistent high risk HPV with abnormal cytology, high grade cytology (moderate or severe dyskaryosis, HSIL), any glandular abnormality, or suspected invasion at any time; low grade cytology with positive HPV.
• Colposcopy with 5 percent acetic acid and Lugol iodine, and directed punch biopsy of the worst areas (adequate depth for stroma). Take endocervical sampling when the transformation zone is not fully visible.
• If the whole transformation zone is visible, treatment may be done on a "see and treat" basis for high grade cytology.
• Histology grading CIN 1, 2, 3, with p16 immunostaining to help classify CIN 2 and distinguish from mimics.

• CIN 1: observation without treatment, with repeat cytology or HPV test at 12 months. Refer back to routine screening if two consecutive tests are negative. Treat if it persists beyond 2 years, or if the colposcopy is unsatisfactory.
• CIN 2: in women under 25 or those wanting future pregnancies, observation for 12 to 24 months with repeat colposcopy every 6 months is reasonable (regression is common); otherwise treat.
• CIN 3 and CIN 2 persistent or in women over 25: treat. Excision is preferred because it provides a specimen for histology (to exclude microinvasion) and margin status.
  • Large loop excision of the transformation zone (LLETZ/LEEP): under local anaesthetic (lidocaine 2 percent with adrenaline, 2 to 5 mL intracervical). Use a loop 15 to 20 mm wide and 8 to 10 mm deep for ectocervical disease, up to 10 to 15 mm depth for lesions extending into the canal, with a modified top hat for glandular lesions. Haemostasis with ball diathermy and Monsel paste.
  • Cold knife cone biopsy: for glandular disease, suspected microinvasion, or when depth and margin precision matters.
  • Ablative treatments (cryotherapy, thermal coagulation, laser vaporisation) are used where excisional facilities are limited and the lesion is fully visible, with no suspicion of invasion or glandular disease.
• Complications: bleeding (primary or secondary at 7 to 14 days, in about 2 to 5 percent), infection, cervical stenosis, and later pregnancy complications.
• Excision depth above 12 mm raises the risk of preterm birth (rises from about 5 percent to about 10 percent at 10 to 15 mm depth and above), and PPROM. Counsel women of reproductive age, and avoid unnecessarily deep or repeat excisions.
• Advise avoidance of intercourse, tampons, and swimming for 4 weeks after treatment.
• Margins: positive margins prompt closer follow up rather than automatic re-excision. In women older than 50 or with positive endocervical margin, re-excision is considered.
• Test of cure: HPV test with or without cytology at 6 months after treatment. If negative, return to screening at 3 years (or 5 years if HPV-based screening) for at least 25 years after treatment.
• Women with positive test of cure go to colposcopy. Recurrence is about 5 to 15 percent.
• Hysterectomy is not a treatment of CIN alone and is used only for coexisting indications or persistent unmanageable disease with completed childbearing.
• Pregnancy: colposcopy is safe, biopsy only if invasion is suspected, and treatment is deferred until 3 months postpartum.
• HPV vaccination: two doses at ages 9 to 14 (0 and 6 to 12 months) or three doses (0, 1 to 2, 6 months) at 15 or over and for immunocompromised persons. Vaccination before and after treatment reduces recurrence.
• Smoking cessation; immunosuppressed women need closer surveillance with higher recurrence.