HUMAN PAPILLOMAVIRUS


See also Warts and Cervical Neoplasms

I. Pathophysiology and epidemiology

  1. HPV subtypes and their clinical correlates:
Subtype Condyloma Dysplasia Malignancy
6* Yes Yes Rare
11** Yes Yes Rare
16*** Yes Yes Yes
18 Yes Yes Yes
31, 33, 35 Yes Yes  
41, 42 Yes    
43 Yes    
44 Yes Yes  
45 Yes Rare  
51 Yes    
52 Yes Yes Yes
53, 54, 55 Unknown Unknown Unknown
56 Yes Yes Yes

*--Associated with laryngeal papillomas
**--Associated with laryngeal and conjunctival papillomas
***--Associated with vulvar and anal cancers

  1. Prevalence of HPV at 3y post-onset of sexual activity in young women is 50%
  2. 90% of HPV infections in adolecent women clear spontaneously within 2y

II. Use of HPV DNA assays as an alternative to pap screening

  1. In a study of 1415 women 35-65yo, self-collected vaginal swab HPV DNA testing ("Hybrid Capture II") had similar sensitivity for HGSIL or Ca "detected during the course of the study" to Pap smear (66.1% vs. 67.9%) but higher false-positive rates (17.1% vs. 12.3%); all women underwent cervicography as well (JAMA 283:81, 2000)
  2. Per 2006 consensus guidelines, may offer primary HPV testing to women over 30yo (not at younger ages); if positive but pap is negative, repeat both in 12mos; if both negative, routine screening need not be performed for another 3y (Wright TC Jr et al. 2006 consensus guidelines for the management of women with abnormal cervical cancer screening tests. Am J Obstet Gynecol 2007 Oct; 197:346 ; these are jointly from: National Institutes of Health, the American Cancer Society, and the American College of Obstetricians and Gynecologists)

III. Use of HPV DNA assays in management of ASCUS paps-See also Management of Abnormal Pap Smears

  1. A series of women had routine paps and simultaneous HPV PCR. 973 had ASCUS pap results and had colpo immediately preceded by repeat pap smear (median 2mo after first pap). Positive HPV PCR was 89% sensitive for histologic dx of HGSIL or Ca on colposcopic bx compared abnormal repeat pap, which had a sensitivity of 76%. Based on the data, the authors estimate that an algorithm of doing HPV PCR on pts with ASCUS paps and referring positives for colpo and doing repeat paps on negatives would be 97% sensitive for HGSIL or Ca (JAMA 281:1605, 1999--JW)
  2. In a study of 3488 women with ASCUS paps, HPV testing of cervical specimens were 96.3% sensitive for CIN 3 or worse as opposed to 85.3% for ASCUS findings on repeat pap or 44.1% for HGSIL on repeat pap (J. Nat. Cancer Inst. 93:293, 2001--JW)

IV. "HPV4" Vaccine (Gardisil-For HPV types 6, 11, 16, and 18, the strains that are oncogenic and also the strains that most commonly cause genital warts)

  1. In a randomized study in 1,1113 women 15-25yo, an HPV-16 & HPV-18 vaccine (x3 over 6mos), compared w/placebo, was ass'd with sig. lower incidence of persistent HPV infection (0% vs. 2%) and abnormal cervical cytology (0.4% vs. 4.9%) (Lancet 364:1757, 2004--JW)
  2. Recommended for all young women starting at age 11-12yo on 3-dose schedule (2nd and 3rd doses given 2mos and 6mos after first, respectively); can be given up to age 26yo
  3. FDA Approved in 2009 for males 9-26yo

V. "HPV2" vaccine (Cervarix, for HPV types 16 and 18, the oncogenic strains)

  1. Same immunization schedule as the HPV4 vaccine