STEPTRACKERREPRODUCTIVE | PATHOLOGY + MICROBIOLOGY | HIGH-YIELD REVIEW

Cervix

HPV at the transformation zone, the dysplasia steps that screening catches, and the invasive cancer that kills by blocking the ureters.

FOCUS ON
High-risk HPV 16, 18: E6 degrades p53, E7 inactivates Rb. Dysplasia starts at the transformation zone: CIN 1 (LSIL, usually regresses) → CIN 2/3 (HSIL) → invasive SCC. Cytology screening + HPV testing; colposcopy for abnormal results; HPV vaccine prevents. Death is usually from ureteral obstruction → renal failure.
TOPIC
MECHANISM
FEATURES
CLUE
High-risk HPV
Types 16, 18, 31, 33, 45; E6 → p53 degradation, E7 → Rb release of E2F
Infects immature squamous cells of the transformation zone (squamocolumnar junction)
Most infections clear within 2 years
Risk factors
More HPV exposure or less clearance
Multiple partners, early first intercourse, smoking, HIV/immunosuppression, long-term OCP use, high parity
Invasive cervical cancer is AIDS-defining
CIN 1 (LSIL)
Dysplasia in the lower third of the epithelium; koilocytes
Usually regresses
Repeat testing, not excision
CIN 2 / CIN 3 (HSIL)
Dysplasia in two-thirds to full thickness (CIN 3 = carcinoma in situ)
Higher progression risk; p16 ⁺
Colposcopy + LEEP / cone excision
Squamous cell carcinoma
most common type
Invasion through the basement membrane
Women 40–50s: postcoital bleeding, abnormal bleeding, discharge, pelvic pain
Lateral spread → ureters → hydronephrosis
Adenocarcinoma
Endocervical glands; HPV 18 more often
~15–25% of cervical cancers; harder to find on cytology
Adenocarcinoma in situ precursor
Spread & cause of death
Direct extension into parametria, bladder, rectum; lymphatics
Iliac and para-aortic nodes; bilateral ureteral obstruction → renal failure
Hydronephrosis = stage IIIB
Screening
Detects dysplasia before invasion
Cytology from 21 every 3 years; ages 30–65: HPV testing every 5 years (or co-testing / cytology every 3)
Abnormal → colposcopy and biopsy
HPV vaccine
Recombinant L1 capsid virus-like particles → neutralizing antibodies
9-valent (6, 11, 16, 18, 31, 33, 45, 52, 58); routine at 11–12 (from age 9), catch-up to 26
Screening continues after vaccination
Cervicitis
Chlamydia, N gonorrhoeae, HSV, Trichomonas
Mucopurulent discharge, friable cervix, postcoital bleeding; strawberry cervix (Trich)
NAAT · treat both chlamydia and gonorrhea
Benign cervical lesions
Blocked endocervical glands; reactive overgrowth
Nabothian cysts (incidental), endocervical polyps (intermenstrual bleeding)
No cancer risk

Mechanism — HPV to invasive carcinoma

HPV infectionTransformation zone
→
Persistent infectionViral DNA integrates
→
E6/E7 expressionp53 and Rb lost
→
CIN 1 → 2 → 3
→
Invasive SCC

Integration disrupts the viral E2 gene, which normally represses E6/E7 — so integrated virus drives continuous oncogene expression.

HPV types and their lesions

HPV TYPE
RISK
LESIONS
6, 11
Low
Genital warts, laryngeal papillomas
16
High
Cervical SCC, oropharyngeal, anal, vulvar, penile SCC
18
High
Cervical adenocarcinoma and SCC
31, 33, 45, 52, 58
High
Cervical dysplasia and cancer
1, 2, 4
Low (skin)
Common and plantar warts

How it's tested

COMMON CONFUSIONKoilocytes show HPV infection, not cancer. Grade (CIN 1 vs 2/3) depends on how much of the epithelium is dysplastic.
THE TRAPA vaccinated woman still needs screening — the vaccine doesn't cover all oncogenic types and doesn't treat existing infection.
YOUR APPROACHHPV type → E6/E7 targets → lesion grade → next step (repeat, colposcopy, excision) → if invasive, watch the ureters and nodes.

If you see… think…

HPV oncoprotein that degrades p53 → E6
HPV oncoprotein that binds Rb → E7
Where cervical dysplasia begins → transformation zone
Pap with LSIL in a 23-year-old → usually regresses — repeat testing
HSIL on cytology → colposcopy with biopsy
Woman with postcoital bleeding and a friable cervical mass → cervical SCC
Cervical cancer with bilateral hydronephrosis → ureteral obstruction — renal failure
HIV-positive woman with invasive cervical cancer → AIDS-defining illness
Strawberry cervix → Trichomonas
Vaccine antigen in the HPV vaccine → L1 capsid protein