Cervical Cancer and HPV

Risk factors

• Persistent high-risk HPV infection (types 16, 18, 31, 33, 45, 52, 58 etc.)
• Early age at first intercourse, multiple sexual partners
• Immunosuppression (HIV, transplant)
• Smoking (squamous more than adeno)
• Long-term combined OCP use
• Multiparity
• DES exposure in utero (clear cell adenocarcinoma)
• Lower socioeconomic status / lack of screening access

Pathophysiology

High-risk HPV E6 and E7 oncoproteins inactivate tumor suppressors p53 and Rb, respectively, leading to genomic instability, immortalization of keratinocytes, and progression through cervical intraepithelial neoplasia (CIN 1 → CIN 2 → CIN 3 → invasive carcinoma). Most HPV infections clear spontaneously within 1-2 years; persistence drives oncogenesis.

Clinical presentation

Differential diagnosis

• Cervicitis — Mucopurulent discharge, friability, GC/CT positive
• Endometrial cancer with cervical extension — Postmenopausal bleeding, endometrial biopsy
• Cervical polyp — Benign protrusion through os; postcoital spotting
• Cervical ectropion — Reddened columnar epithelium on ectocervix; normal
• Vaginal cancer (extending to cervix) — Rare; imaging and biopsy
• Cervical fibroid — Firm mass; ultrasound

Diagnostic workup

Diagnostic algorithm

flowchart TD
  A[Abnormal cervical cytology<br/>or HPV] --> B{Result}
  B -->|ASC-US| C[Reflex HPV testing]
  C -->|HPV positive| D[Colposcopy + biopsy]
  C -->|HPV negative| E[Routine surveillance]
  B -->|LSIL| F[Colposcopy<br/>± surveillance if low risk]
  B -->|HSIL / ASC-H / AGC| D
  D --> G{Biopsy result}
  G -->|CIN 1| H[Surveillance<br/>most regress]
  G -->|CIN 2-3 / HSIL| I[Excisional procedure:<br/>LEEP or cold knife cone]
  G -->|Invasive cancer| J[FIGO staging:<br/>exam, MRI, PET-CT]
  J --> K{Stage}
  K -->|IA1| L[Conization or<br/>simple hysterectomy]
  K -->|IA2-IB1| M[Radical hysterectomy<br/>+ lymphadenectomy]
  K -->|IB2-IVA| N[Concurrent<br/>chemoradiation + brachy]
  K -->|IVB / recurrent| O[Systemic therapy<br/>± immunotherapy]

Treatment

Complications

• Hydronephrosis from parametrial invasion (uremia is a common cause of death in advanced disease)
• Lymphedema after lymphadenectomy or radiation
• Vaginal stenosis and sexual dysfunction post-radiation
• Fistula formation (vesicovaginal, rectovaginal)
• Pregnancy complications after conization (cervical insufficiency, preterm birth)
• Recurrence (highest in first 2 years)

PANCE pearls

• Persistent HPV infection (not transient) drives cervical cancer — most HPV infections clear spontaneously within 1-2 years.
• HPV vaccination is most effective before sexual debut but is beneficial through age 26 and selectively to 45.
• Co-testing (cytology + HPV) every 5 years has equivalent or better sensitivity than annual cytology with less screening burden.
• Adenocarcinoma of cervix is more often missed on cytology than squamous cell carcinoma — HPV testing has higher sensitivity for adeno precursors.
• Cisplatin-based chemoradiation is the standard for locally advanced disease; brachytherapy is essential for optimal cure rates.
• Cervical cancer in pregnancy requires individualized multidisciplinary care; treatment delay until fetal maturity is often appropriate for early-stage disease.

References

• USPSTF 2018 — Screening for Cervical Cancer: USPSTF Recommendation Statement (JAMA 2018)
• ACS 2020 — Cervical Cancer Screening for Individuals at Average Risk: 2020 Guideline Update From the American Cancer Society (Fontham et al., CA Cancer J Clin 2020)
• ASCCP 2019 — 2019 ASCCP Risk-Based Management Consensus Guidelines for Abnormal Cervical Cancer Screening Tests (Perkins et al., J Low Genit Tract Dis 2020)
• ACIP HPV 2019 — Human Papillomavirus Vaccination for Adults: ACIP Updated Recommendations (MMWR 2019)
• FIGO 2018 — FIGO 2018 Staging System for Cervical Cancer (Bhatla et al., Int J Gynaecol Obstet 2019)