Cervical Intraepithelial Neoplasia
Summary
Cervical intraepithelial neoplasia (CIN) is a pre-malignant condition of the cervical epithelium, representing abnormal cell changes that may progress to cervical cancer if untreated. CIN is caused by persistent infection with high-risk human papillomavirus (HPV), particularly types 16 and 18. It is detected through cervical screening programmes (PAP smear or HPV testing) and confirmed by colposcopy with biopsy. CIN is graded 1-3 based on the proportion of epithelium involved by dysplastic cells. CIN 1 often regresses spontaneously; CIN 2/3 requires treatment, usually by excision (LLETZ). The introduction of HPV vaccination has dramatically reduced CIN incidence in vaccinated populations. CGIN (cervical glandular intraepithelial neoplasia) is the glandular equivalent and is more difficult to diagnose and treat due to skip lesions.
Key Facts
- Cause: High-risk HPV (types 16, 18 account for ~70% of cervical cancers)
- CIN 1: Lower 1/3 of epithelium affected; ~60% regress spontaneously
- CIN 2: Lower 2/3 of epithelium; ~40% regress, ~20% progress
- CIN 3: Full thickness (carcinoma in situ); ~30% progress to invasion over 10-20 years
- Detection: Cervical screening → Colposcopy → Biopsy
- Treatment: LLETZ (Large Loop Excision of Transformation Zone) for CIN 2/3
- Test of cure: HPV test at 6 months post-treatment
- CGIN: Glandular equivalent; harder to diagnose; requires cone biopsy
- Vaccination: HPV vaccine prevents ~90% of cervical cancers
Clinical Pearls
"HPV Is the Necessary Cause": Virtually all cervical cancer is caused by high-risk HPV. Persistent infection leads to CIN; clearance leads to regression. Most women clear HPV within 2 years.
"CIN 1 = Watch and Wait": CIN 1 is low-grade and most cases regress spontaneously. Management is typically surveillance with repeat cytology/colposcopy. Treatment only if persistent >2 years.
"CIN 3 Is Carcinoma In Situ": CIN 3 represents full-thickness dysplasia and is considered carcinoma in situ. Without treatment, significant risk of progression to invasive cancer over 10-30 years.
"LLETZ Is Gold Standard": Large Loop Excision of the Transformation Zone uses a thin wire loop with electrical current to excise the abnormal area. It's diagnostic (histology) and therapeutic. See-and-treat at colposcopy is common practice.
"CGIN: Skip Lesions = Challenges": Cervical glandular intraepithelial neoplasia is in the endocervical canal and can have skip lesions (multifocal disease). Cone excision with clear margins is required; follow-up is more intensive.
Why This Matters Clinically
Cervical screening programmes have dramatically reduced cervical cancer mortality. Understanding the CIN pathway, HPV's role, colposcopy findings, and treatment options is essential for all clinicians managing women's health. Early detection and treatment of CIN prevents cervical cancer.[1,2]
Incidence & Prevalence
| Parameter | Data |
|---|---|
| CIN prevalence | ~2-3% of screened women have abnormal cytology |
| High-grade CIN (CIN 2/3) | ~0.5% of screened women |
| Cervical cancer incidence (UK) | ~3,200 new cases/year |
| Peak age for CIN | 25-35 years |
| Trend | Declining (screening + HPV vaccination) |
Risk Factors
| Factor | Risk | Notes |
|---|---|---|
| HPV infection | Essential cause | HR-HPV types 16, 18, 31, 33, 45, etc. |
| Immunosuppression | Increased | HIV, transplant, immunosuppressive drugs |
| Smoking | 2-3x | Independent risk factor; carcinogens concentrate in cervical mucus |
| Multiple sexual partners | Increased HPV exposure | |
| Early sexual debut | Increased | Immature transformation zone more susceptible |
| High parity | Modestly increased | Hormonal and mechanical factors |
| Oral contraceptive use (long-term) | Modestly increased | >5 years use |
| Co-infection (Chlamydia, HSV) | Increased |
HPV and Cervical Neoplasia
Step 1: HPV Infection
- HPV infects basal epithelial cells via micro-abrasions in the transformation zone
- Most infections are transient; 90% clear within 2 years
Step 2: Persistent Infection
- Failure to clear HPV (persistent infection >1-2 years)
- High-risk HPV types (16, 18) integrate into host DNA
Step 3: Oncogene Expression
- HPV E6 and E7 oncoproteins inactivate tumour suppressors:
- E6 → Degrades p53 (prevents apoptosis)
- E7 → Inactivates Rb (uncontrolled cell cycle)
- Results in genomic instability
Step 4: CIN Development
- Dysplastic cells develop in the transformation zone
- Graded by proportion of epithelium involved:
- CIN 1: Lower 1/3
- CIN 2: Lower 2/3
- CIN 3: Full thickness (carcinoma in situ)
Step 5: Invasion (If Untreated)
- CIN 3 can progress through basement membrane → Invasive carcinoma
- Timeline: 10-30 years (slower than many cancers)
Transformation Zone
| Feature | Details |
|---|---|
| Location | Junction of ectocervix (squamous) and endocervix (glandular) |
| Importance | Most cervical neoplasia arises here |
| Squamous metaplasia | Normal process; glandular replaced by squamous epithelium |
| Why vulnerable | Actively dividing metaplastic cells more susceptible to HPV |
CIN Grading
| Grade | Epithelial Involvement | Regression | Progression to Cancer |
|---|---|---|---|
| CIN 1 (Low-grade) | Lower 1/3 | ~60% | <1% |
| CIN 2 | Lower 2/3 | ~40% | ~5% |
| CIN 3 (High-grade) | Full thickness | ~30% | ~30% over 30 years |
Typical Presentation
CIN is asymptomatic — detected through screening, not symptoms.
| Finding | Notes |
|---|---|
| Abnormal screening result | Cytology (dyskaryosis) or HPV-positive |
| No symptoms | CIN itself is silent |
Symptoms Suggesting Invasive Cancer
[!CAUTION] Red Flags — Suspect Invasion:
- Post-coital bleeding
- Intermenstrual bleeding
- Post-menopausal bleeding
- Abnormal vaginal discharge (offensive, watery, blood-stained)
- Pelvic pain (advanced)
- Visible cervical lesion on examination
Screening Results Leading to Colposcopy
| Cytology Result | Action |
|---|---|
| High-grade dyskaryosis (moderate/severe) | Urgent colposcopy |
| Low-grade dyskaryosis | Colposcopy if HPV-positive |
| Borderline/ASCUS | HPV triage; colposcopy if positive |
| HPV-positive, normal cytology | Repeat HPV test at 12 months |
Speculum Examination
| Finding | Significance |
|---|---|
| Normal appearance | CIN is often invisible to naked eye |
| Acetowhite change | May be seen with application of acetic acid (colposcopy) |
| Visible lesion | Suggests invasive cancer; urgent referral |
| Contact bleeding | May indicate significant pathology |
Colposcopy
Colposcopy is the gold standard for diagnosing CIN. Uses magnification (6-40x) with application of acetic acid (3-5%) and Lugol's iodine (Schiller's test).
Acetic Acid Changes:
| Finding | Interpretation |
|---|---|
| Acetowhite epithelium | Abnormal (dysplastic) tissue turns white |
| Dense acetowhite | More likely high-grade |
| Sharp margins | More likely high-grade |
| Punctation | Abnormal capillaries viewed end-on (dots) |
| Mosaic pattern | Abnormal capillaries in network pattern |
| Atypical vessels | Suggests invasion |
Lugol's Iodine (Schiller's Test):
| Finding | Interpretation |
|---|---|
| Brown staining | Normal glycogen-containing epithelium |
| Non-staining (Schiller-positive) | Abnormal tissue; lacks glycogen |
Colposcopy Adequacy
| Factor | Adequate | Inadequate |
|---|---|---|
| Transformation zone visualised | Fully seen | Not fully visible |
| Squamocolumnar junction | Seen in entirety | Cannot be seen (type 3 TZ) |
| Implications | Can biopsy or treat | May need excision for diagnosis |
Cervical Screening
| Test | Role |
|---|---|
| HPV testing (primary) | Detects high-risk HPV DNA; used as primary screening in England |
| Cytology (LBC) | Triage for HPV-positive women; identifies dyskaryosis grade |
Colposcopy and Biopsy
| Investigation | Purpose |
|---|---|
| Colposcopy | Visual examination with magnification + acetic acid |
| Punch biopsy | Histological diagnosis; grades CIN 1/2/3 |
| LLETZ biopsy | Excisional biopsy; both diagnostic and therapeutic |
Histology Reporting
| Term | Definition |
|---|---|
| CIN 1 | Low-grade squamous intraepithelial lesion (LSIL) |
| CIN 2 | High-grade squamous intraepithelial lesion (HSIL) |
| CIN 3 | High-grade (carcinoma in situ); HSIL |
| CGIN/AIS | Glandular neoplasia (adenocarcinoma in situ) |
Management Algorithm
CIN MANAGEMENT PATHWAY
↓
┌─────────────────────────────────────────────────────────────┐
│ CERVICAL SCREENING RESULT │
├─────────────────────────────────────────────────────────────┤
│ HPV NEGATIVE: │
│ ➤ Routine recall (3-5 years depending on age) │
│ │
│ HPV POSITIVE + NORMAL CYTOLOGY: │
│ ➤ Repeat HPV test at 12 months │
│ ➤ If still positive at 24 months → Colposcopy │
│ │
│ HPV POSITIVE + ABNORMAL CYTOLOGY: │
│ ➤ Refer for colposcopy │
│ │
│ HIGH-GRADE DYSKARYOSIS: │
│ ➤ Urgent colposcopy │
└─────────────────────────────────────────────────────────────┘
↓
┌─────────────────────────────────────────────────────────────┐
│ COLPOSCOPY │
├─────────────────────────────────────────────────────────────┤
│ ➤ Visual assessment with acetic acid/iodine │
│ ➤ Biopsy abnormal areas │
│ ➤ "See and treat" if high-grade suspected │
│ │
│ COLPOSCOPY FINDINGS → BIOPSY → HISTOLOGY │
└─────────────────────────────────────────────────────────────┘
↓
┌─────────────────────────────────────────────────────────────┐
│ HISTOLOGY RESULT │
├─────────────────────────────────────────────────────────────┤
│ CIN 1 (LOW-GRADE): │
│ ➤ Conservative management (surveillance) │
│ ➤ Repeat cytology/HPV at 12 months │
│ ➤ Colposcopy if persistent >2 years │
│ ➤ Treatment only if persistent or patient preference │
│ │
│ CIN 2: │
│ ➤ Treat (LLETZ) OR │
│ ➤ Observe in young women if limited disease │
│ │
│ CIN 3 (HIGH-GRADE): │
│ ➤ Excision required (LLETZ, cone biopsy) │
│ ➤ Clear margins essential │
│ │
│ CGIN/AIS: │
│ ➤ Cone biopsy with clear margins │
│ ➤ Consider hysterectomy if family complete │
└─────────────────────────────────────────────────────────────┘
↓
┌─────────────────────────────────────────────────────────────┐
│ TREATMENT: LLETZ │
├─────────────────────────────────────────────────────────────┤
│ ➤ Large Loop Excision of Transformation Zone │
│ ➤ Outpatient procedure under local anaesthesia │
│ ➤ Wire loop excises transformation zone │
│ ➤ Specimen sent for histology │
│ ➤ Hemostasis with diathermy or Monsel's solution │
│ │
│ POST-PROCEDURE ADVICE: │
│ ➤ Watery discharge for 4-6 weeks │
│ ➤ Avoid tampons, intercourse, swimming for 4 weeks │
│ ➤ Seek help if heavy bleeding, smelly discharge, fever │
└─────────────────────────────────────────────────────────────┘
↓
┌─────────────────────────────────────────────────────────────┐
│ TEST OF CURE │
├─────────────────────────────────────────────────────────────┤
│ ➤ HPV test at 6 months post-treatment │
│ ➤ If HPV negative: Return to routine screening │
│ ➤ If HPV positive: Repeat cytology at 12 months │
│ ➤ If persistent HPV at 12 months: Colposcopy │
└─────────────────────────────────────────────────────────────┘
Treatment Options
| Treatment | Indication | Notes |
|---|---|---|
| LLETZ | CIN 2/3; High-grade lesions | Outpatient; diagnostic and therapeutic |
| Cone biopsy | CGIN; Type 3 TZ; discordance | Larger excision; theatre |
| Cold coagulation | CIN 1-2; small lesions | Ablative; no histology |
| Laser ablation | CIN 1-2 | Ablative; no histology |
| Hysterectomy | CGIN with complete family; recurrent disease | Only if margins persistently involved |
Treatment Complications
| Complication | Incidence | Management |
|---|---|---|
| Primary haemorrhage | 2-5% | Pressure, cautery, suture |
| Secondary haemorrhage (delayed) | 2-3% | Usually self-limiting; cautery if severe |
| Infection | 1-2% | Antibiotics |
| Cervical stenosis | Rare | Dilatation if symptomatic |
| Preterm birth (obstetric) | Increased | Counsel; cervical length surveillance |
Obstetric Implications of LLETZ
| Factor | Impact |
|---|---|
| Preterm birth | Increased risk (RR ~1.5-2) with large excisions |
| Cervical weakness | May require cervical cerclage |
| Cervical stenosis | Rare; may affect labour |
Natural History
| Grade | Regression | Persistence | Progression to Invasion |
|---|---|---|---|
| CIN 1 | ~60% | ~30% | <1% |
| CIN 2 | ~40% | ~40% | ~5% |
| CIN 3 | ~30% | ~50% | ~30% over 30 years |
Outcomes After Treatment
| Outcome | Rate |
|---|---|
| Cure (HPV-negative at 6 months) | ~90% |
| Recurrence | ~5-10% |
| Progression to cancer (post-treatment) | <1% |
Key Guidelines
| Guideline | Organisation | Year | Key Points |
|---|---|---|---|
| NHS Cervical Screening Programme (NHSCSP) | PHE/UKHSA | Ongoing | HPV primary screening; colposcopy pathways |
| BSCCP Guidelines | British Society for Colposcopy | 2020 | Colposcopy management protocols |
| NICE | National Institute for Health and Care Excellence | Various | Cervical screening and referral |
Landmark Evidence
HPV Vaccination Impact (Falcaro et al. 2021)
- HPV vaccination programme in England reduced cervical cancer by 87% in women vaccinated at age 12-13
- Landmark real-world evidence for vaccine effectiveness
- PMID: 34741816
HPV Primary Screening (Ronco et al. 2014)
- HPV testing is more sensitive than cytology for detecting CIN 2+
- 60-70% greater sensitivity
- PMID: 24499816
What is CIN?
CIN (cervical intraepithelial neoplasia) means abnormal changes in the cells on the surface of your cervix. It is NOT cancer, but if left untreated, it could develop into cervical cancer over many years.
What causes it?
CIN is caused by the human papillomavirus (HPV), a very common sexually transmitted infection. Most people with HPV clear it naturally, but in some women, the virus persists and causes cell changes.
How is it found?
CIN is usually found through cervical screening (smear tests). If abnormal cells are detected, you will be referred for a colposcopy — a closer look at your cervix using a microscope.
What do the grades mean?
- CIN 1: Mild changes — usually go away on their own; you'll be monitored
- CIN 2: Moderate changes — treatment is usually recommended
- CIN 3: Severe changes — treatment is definitely needed
What is the treatment?
The most common treatment is LLETZ (Loop Excision), where a small area of the cervix is removed using a heated wire loop. It's done as an outpatient procedure under local anaesthetic.
After treatment
- You may have a watery discharge for a few weeks
- Avoid tampons, sex, and swimming for about 4 weeks
- You'll have a follow-up test at 6 months to check everything has cleared
Prevention
The HPV vaccine protects against the types of HPV that cause most cervical cancers and CIN. It's offered to girls and boys aged 12-13 in the UK.
Guidelines
-
NHS Cervical Screening Programme. gov.uk/cervical-screening
-
White C, et al. BSCCP Colposcopy and Programme Management Guidelines. 2020. bsccp.org.uk
Key Studies
-
Falcaro M, Castañon A, Ndela B, et al. The effects of the national HPV vaccination programme in England, UK, on cervical cancer and grade 3 cervical intraepithelial neoplasia incidence. Lancet. 2021;398(10316):2084-2092. PMID: 34741816
-
Ronco G, Dillner J, Elfström KM, et al. Efficacy of HPV-based screening for prevention of invasive cervical cancer. Lancet. 2014;383(9916):524-532. PMID: 24499816
High-Yield Exam Topics
| Topic | Key Points |
|---|---|
| HPV role | HR-HPV (16, 18) causes 70% of cervical cancer; E6/E7 oncoproteins |
| CIN grading | 1 = lower 1/3; 2 = lower 2/3; 3 = full thickness |
| CIN 1 management | Surveillance (60% regress); treat only if persistent |
| CIN 2/3 treatment | LLETZ (diagnostic and therapeutic) |
| Colposcopy findings | Acetowhite, punctation, mosaic, atypical vessels |
| Test of cure | HPV test at 6 months post-LLETZ |
| CGIN | Glandular; skip lesions; cone excision |
Sample Viva Questions
Q1: A 28-year-old is referred with high-grade dyskaryosis. Describe your management.
Model Answer: High-grade dyskaryosis requires urgent colposcopy. At colposcopy, I would assess the transformation zone with acetic acid, looking for acetowhite changes, punctation, and mosaic patterns. If the appearance is consistent with high-grade CIN and the transformation zone is fully visualised, I would perform a "see-and-treat" LLETZ under local anaesthesia. The specimen is sent for histology. Post-procedure advice: watery discharge for 4-6 weeks, avoid tampons/intercourse for 4 weeks. Test of cure HPV at 6 months; if negative, return to routine screening.
Q2: What are the colposcopic features of CIN?
Model Answer: After applying 3-5% acetic acid:
- Acetowhite epithelium: Abnormal tissue turns white (coagulation of nuclear proteins)
- Punctation: Ends of abnormal capillaries seen as dots
- Mosaic: Network pattern of abnormal vessels
- Sharp margins: High-grade lesions have well-demarcated edges
- Dense white: More likely high-grade
After Lugol's iodine (Schiller's test):
- Normal tissue stains brown (glycogen); abnormal tissue does not stain (Schiller-positive)
Q3: What is CGIN and how does it differ from CIN?
Model Answer: CGIN (Cervical Glandular Intraepithelial Neoplasia) is the glandular equivalent of CIN, arising from the endocervical columnar epithelium. Key differences: CGIN occurs in the endocervical canal (harder to visualise); it can have skip lesions (multifocal, non-contiguous); it is associated with higher risk of developing adenocarcinoma. Diagnosis requires excisional biopsy (cone or LLETZ) rather than punch biopsy. Management: Cone biopsy with clear margins is essential. If margins are involved, repeat excision or hysterectomy may be required. Follow-up is more intensive.
Common Exam Errors
| Error | Correct Approach |
|---|---|
| Treating all CIN 1 | CIN 1 usually managed conservatively; 60% regress |
| Forgetting HPV test of cure | HPV test at 6 months is standard post-LLETZ |
| Confusing cytology and histology terms | Cytology: Dyskaryosis; Histology: CIN |
| Missing CGIN skip lesion concept | CGIN can be multifocal; needs excision not ablation |
Last Reviewed: 2025-12-24 | MedVellum Editorial Team
Medical Disclaimer: MedVellum content is for educational purposes and clinical reference. Clinical decisions should account for individual patient circumstances. Always consult appropriate specialists.