Dermatology MCQ - Viral Infections - HPV-associated neoplasias of genitalia and mucosae

A 35-year-old woman presents for a routine Pap smear. She has a history of genital warts in her 20s but has been asymptomatic for years. The cytology report shows "high-grade squamous intraepithelial lesion (HSIL)" with koilocytic changes. Colposcopy-directed biopsy confirms cervical intraepithelial neoplasia grade 3 (CIN3). Which of the following HPV types is most strongly associated with this lesion and its potential for progression to invasive carcinoma?

A) HPV 6
B) HPV 11
C) HPV 16
D) HPV 42
E) HPV 53

Correct Answer: C) HPV 16

Explanation

This scenario describes a high-grade cervical precancerous lesion (CIN3) with a high risk of progression to invasive cervical cancer, most commonly associated with high-risk HPV types.

Key Features of HPV-Associated Neoplasia:

• Pathology:

  • Koilocytic changes: Perinuclear halos and nuclear hyperchromasia/atypia ("koilocytes") are cytopathic effects of HPV infection.

  • CIN3: Full-thickness dysplasia (carcinoma in situ), with a significant risk of progression to invasive cancer if untreated.

• Oncogenic HPV Types:

  • High-risk (oncogenic) types: HPV 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68.

  • Highest risk: HPV 16 is responsible for ~50-60% of cervical cancers and is the most common type found in high-grade lesions (CIN2/3). HPV 18 is the second most common.

  • Low-risk types: HPV 6 and 11 cause ano-genital warts (condylomata) and low-grade lesions but are rarely found in invasive cancers.

Why Not the Other Options?

• (A) HPV 6 & (B) HPV 11: Low-risk types associated with genital warts and low-grade CIN1 lesions. They have minimal oncogenic potential.

• (D) HPV 42: A low-risk type occasionally found in genital warts but not high-grade neoplasia.

• (E) HPV 53: Classified as "possibly oncogenic" but is much less common and less potent than HPV 16 in causing high-grade lesions.

Management of CIN3:

• Excisional procedure: Loop electrosurgical excision procedure (LEEP) or cold knife conization to remove the transformational zone and rule out invasion.

• Follow-up: Increased surveillance with HPV testing and cytology post-treatment.

• Prevention: HPV vaccination (Gardasil 9) targets HPV 16/18 and 5 other high-risk types, plus HPV 6/11.

Prognosis:
With treatment, the risk of progression to cancer is greatly reduced. However, persistent high-risk HPV infection requires lifelong monitoring.

Note: While HPV 16 is the most common driver of cervical cancer, other high-risk types (e.g., 18, 31, 33) are also significant. HPV testing is part of routine cervical cancer screening.