**Appearance of Condyloma Acuminatum:
**Hyperkeratotic, Firm Exophilic Papules that can be 1mm-2 cm caused by HPV
Symptoms of Condyloma Acuminatum:
75% asymptomatic otherwise itching, pain and burning
Differentiating between normal tissue and cervical wart in clinical setting:
Use of 3-5% acetic acid > turns wart tissue white while surrounding tissue remains flesh-colored.
Laryngeal Papillomas/Respiratory Papillomatosis:
Caused by HPV 6 or 11, nodules on the ciliated and squamous epithelial junction of the larynx
Laryngeal Papillomas/Respiratory Papillomatosis Symptoms:
Altered cry, Hoarseness, Stridor, Respiratory Distress, (common in children)
Laryngeal Papillomas and babies:
C-section NOT proven to reduce prevention of HPV infection. Surgical removal necessary.
HPV Virus Family:
Papovaviridae
**HPV Virus Genome (?) and Envelope (?)
Non-enveloped dsDNA
HPV Pathology in Warts:
Basal epithelium: site of PRIMARY infection > viral gene expression > viruses assembled > Virus shed from skin when most differentiated tissue is sloughed off surface. REQUIRES 3-Dimensional Differentiation
Two broad HPV groups:
Cutaneous infection, Mucosal infection
HPV-16 makes up what % of Cervical cancer cases:
49%
Second most common HPV serotype associated with cervical cancer:
HPV-18
General HPV Life Cycle and Cancer:
There is NOT virus PRODUCTION/genome amplification, instead there is genome INTEGRATION with increased E6 and E7 gene production.
HPV Life Cycle with Warts:
CIRCULAR with E2 serving as a NEGATIVE regulator of E6 and E7. E2 binds to promoter sequence only allowing minimal E6/E7 production.
HPV Life Cycle with Cancer:
LINEAR with INTEGRATION of virus. No E6/E7 regulation by E2 > up regulation of E6 + E7 production> proliferation and possible mutations contribute to cancer formation. VIRUS PRODUCTION MINIMIZED
Pathogenesis of E6 + E7 with Cervical Cancer:
HPV E7= inactivates Rb, HPV E6 inactivates p53. NO REGULATION FROM G1 > S phase for cell > increased replication and proliferation
Between what ages is there peak incidence of HPV in the genital tract?
15-25 years old
HPV-infected cervix and Precancerous lesions:
BOTH can REGRESS to previous state. Precancerous lesion> HPV-cervix > normal cervix.
Initial infection with HPV infection in cross section shows:
CIN1: Very mild/mild dysplasia and Low grade squamous intraepithelial Lesion (LSIL) with virus production
Diagnosis of HPV (3):
Clinical appearance usually sufficient. Pap Smear: Hyperkeratosis + KOILOCYTES are histological markers. PCR used for HPV serotypes.
**Abnormal Pap Smear:
Presence of KOILOCYTES: enlarged keratinocytes that contain irregular hyper chromatic nuclei surrounded by a characteristic HALO.
What age to start screening for cervical cancer:
21 years old
Treatment of Genital Warts caused by HPV:
Cryotherapy or CO2 laser.
Treatment of Low Grade Lesions caused by HPV (4):
Cryotherapy, CO2 laser, Loop excision, or Cauterization
Treatment of High Grade Lesions Caused by HPV (3):
Hysterectomy, Radiation, or Chemotherapy
HPV Prevention: Gardasil:
Quadrivalent- protects from 6, 11, 16, 18
HPV Vaccines prepared from:
Viral Capsid Protein= L1, made in yeast
**HPV Prevention: Cervarix:
Bivalent- protects against **16+ 18
Recommendation for girls and HPV vaccination:
Universal vaccination with EITHER quad or bivalent vaccine for all 11-12 year old girls.
Recommendation for boys and HPV vaccination:
Universal vaccination with ONLY QUADRIVALENT vaccine for all 11-12 year olds.
HPV Serotypes associated with Laryngeal Papillomas:
HPV 6 + 11
HIGH RISK HPV Serotypes Associated With Anogenital warts:
HPV 16, 18, 31, 33
LOW RISK HPV Serotypes Associated with Anogenital Warts:
HPV 6 + 11