Rachel Winer, PhD, MPH, Department of Epidemiology, University of Washington,rlw@u.washington.edu

University of Michigan March 15, 2004

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Human Papillomavirus (HPV)

DNA virus

Over 100 HPV types

>40 genital HPV types

Genital / Mucosal HPV Types

  • 6, 11
  • Genital warts, low grade lesions, recurrent respiratory papillomatosis (RRP)
  • Low (negligible)
  • 40, 42, 54, 55/44, 61, 70, 72, 81, CP6108
  • low grade lesions
  • Low (negligible)
  • 16, 18, 26, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66, 68, 73, 82/IS39
  • low grade lesions, high grade lesions, cancer
  • High
  • Uncertain cancer potential: HPV 57, 62, 64/34, 67, 69, 71, 83, 84
  • -
  • Cancer potential: Muñoz et al., Vaccine 2006; 24S3:S3/1

Modes of Transmission
  • SKIN contact, not blood or bodily fluids
  • Sexual
  • Intercourse (vaginal or anal) – (most common route)
  • Genital (non-penetrative), oral, digital contact
  • Non-sexual
  • Mother to newborn (vertical transmission – rare)
  • Auto-innoculation
Probably important for site-site transmission
Epidemiology of HPV

The most common STD in the US and worldwide

80% sexually active adults in the US infected with at least one HPV type by age 501

Estimated incidence: 6.2 million per year1

1 Centers for Disease Control and Prevention. Rockville, Md: CDC National Prevention Information Network; 2004

Prevalence of low-risk and high-risk HPV among 4150 14-59 year old females, NHANES 2003-2006

Hariri S et al. Prevalence of Genital HPV among Females in the United States, the National health and Nutrition Examination Survey, 2003-2006 J Infect Dis. 2011; 204: 566-573

Reused with permission: Oxford University Press on behalf of the Infectious Diseases Society of America 2011

Female Risk of Acquiring Genital HPV Infection from her First Male Sex Partner

Winer et al. J Infect Dis. 2008; 197: 279-82


* From date of first reported vaginal intercourse with a male partner (Women were censored at reported date of a second sex partner)

HPV in Virgins
  • 2-year cumulative incidence of genital HPV in female university students
  • Non-virgins: 38.8%
  • Virgins who initiated vaginal intercourse: 38.9%
  • Virgins who remained virgins: 2.4%
    • Non-penetrative sexual contact was associated with increased risk in virgins.

Winer et al, AJE 2003; 157: 218-26

Duration of HPV Infections
  • Vast majority of infections resolve spontaneously (90% within 2 years)
  • Duration of infections seems to be shorter in men than in women
  • Can't be sure whether an infection has "cleared" or become "latent"

Duration of HPV Infections
  • In newly sexually active female university students, 90% of new infections cleared within 2 years (half cleared within 9.4 months).1
  • 19% of "cleared" infections were re-detected within 1 year.

1 Winer et al. Cancer Epi Bio Prev 2011; 20: 699-707

Risk Factors for HPV Infection in Women
  • Recent new partners
  • Increased risk with new partners reported in the past year
  • Time having known a partner before sex
  • Women knowing their partners for <8 months at greater risk than women knowing their partners for >8 months
  • Sex partner's number of previous partners
  • Increased risk with one or more partners
  • Even greater risk if the number of previous partners was unknown!
  • Inconsistent condom use with new partners

Association between incident HPV infection and condom use over the past 8 months

(Winer et al. N Eng J Med 2006; 354: 2645-54)

Newly sexually active HPV naïve female university students who used condoms consistently (100% of time) reduced their risk of acquisition by 70%.*

Those who used condoms at least half the time reduced their risk of acquisition by 50%.*

* Compared to those who used condoms < 5% of the time, adjusting for numbers of new partners and number of partners' new partners.

Incidence of Genital HPV Infection by Anatomic Site Among Sexually Active Male University Students (18-23 Years Old)

(Partridge et al. JID, 2007; 196: 1128-36)


Circumcision and HPV?
  • A meta-analysis of 21 studies (including 2 RCTs in Africa) showed that HPV was less prevalent in circumcised than uncircumcised men (OR=0.6, 95% CI: 0.4-0.8)1
  • No effect on HPV acquisition or clearance
  • A longitudinal in young heterosexual men showed no effect on overall HPV acquisition, but multi-focal genital infection was more common in uncircumcised men.2
  • Does it affect men's susceptibility to infection and/or infectivity and persistence?

1 Albero et al, Sex Transm Dis 2012; 39: 104-113

2 Vanbuskirk et al, Sex Transm Dis 2011; 38: 1074-81

Transmission Dynamics
  • HPV not restricted to "core groups"
  • Concurrency and serial monogamy likely increase rate of transmission
  • HPV is more transmissible than other viral STDs, but similar to bacterial STDs
  • Male-to-female less efficient than female-to-male

Presentations with warts in men and women < 21 years, and MSM all ages, July 2004 to end June 2011


Read TRH et al Sex Transm Infect doi: 1136/sextrans-2011-050234

© 2011 by BMJ Publishing Group Ltd. Reused with permission

HPV in mid-adult women
  • Are mid-adult women at risk for new HPV infections, or are the majority of "new" infections due to reactivation or persistence of infections acquired at younger ages?
  • It is impossible to distinguish between new infection and reactivation
  • There are no perfect markers of prior infection

Risk of incident high-risk HPV infection in female mid-adult online daters (n=421)1

  • Sexual activity in prior 6 months
  • Hazard ratio
  • Not sexually active with male partners
  • 1.0
  • Sex with 1 male partner who was not new
  • 1.2 (0.7-2.3)
  • Sex with new partner(s) or multiple partners
  • 3.0 (1.7-5.2)

1 Winer et al. Abstract presented at IPV conference, Berlin, Germany

HPV Reactivation from Latency
  • In HIV+ women who were not recently sexually active, low CD4+ T-cell count was associated with HPV incidence.1
  • Age-related / post-menopausal immune senescence may contribute to increased persistence or reactivation of latent infections.

1 Strickler et al. J Natl Cancer Inst 2005; 97: 577-586

Does re-infection occur?
  • Neutralizing antibodies likely protect against re-infection with the same HPV type.
  • Difficult to distinguish re-infection from re-activation.
  • Limited epidemiologic data for and against.
HPV in non-genital sites
HPV in Fingers
  • HPV detected on fingers of 38% of women and 64% of men with genital warts.1
  • The 2-year cumulative incidence of HPV in fingernail tips was 32% in male university students.2
  • 14% of fingernail tip samples from female university students were HPV+.3
    • The same HPV type was concurrently detected in 60% of vaginal samples.
    • Re-detection at the next visit was less common in fingernail samples (15%) than in vaginal samples (73%).

1 Sonnex et al Sex Transm Infect 1999; 75: 317-9

2 Partridge et al J Infect Dis 2007; 196: 1128-36

3 Winer et al Cancer Epi Bio Prev 2010; 19: 1682-5

HPV in Fingers
  • True infection?
  • Deposition?
  • Autoinnoculation?

  • In a small study of 25 heterosexual couples, the rate of autoinoculation (between genitals, anus, hands) in men was comparable to the rate of female-to-male transmission.1
  • In female university students, vaginal HPV infections tended to precede cervical infections.2

1 Hernandez et al Emerging Infectious Diseases 2008; 14: 888-94

2 Winer et al AJE 2003; 157: 218-26

Oral HPV
  • HPV linked to oropharyngeal squamous cell carcinomas (OSCCs) (approx. 90% due to HPV16)1
  • Incidence of OSCCs is increasing and expected to surpass that of cervical cancer by 2020.2

1 D'Souza et al. N Engl J Med 2007; 356(19): 1944-56

2 Chaturvedi et al. J Clin Oncol 2011; 29(32): 4294-301

Oral HPV Prevalence
  • National survey of healthy individuals aged 14 – 69 years:1
    • Any HPV: 6.9%
    • HPV16: 1%
    • Prevalence higher in men (10.1%) than in women (3.6%)
    • Bimodal age distribution (peak prevalence in adults aged 30 – 34 and 60 – 64 years)

1 Gillison et al. JAMA 2012; 15(307): 693 – 703

Oral HPV Transmission
  • Oral HPV is predominantly sexually transmitted.
  • Oral HPV prevalence 8-fold higher in sexually experienced individuals, and associated with lifetime numbers of sexual partners.1
  • Link between oral sex behaviours / open mouth kissing partners and oral HPV is inconclusive.
  • Smoking, immunosuppression, and genital HPV infection have also been associated with oral HPV.
  • Data on oral HPV acquisition and natural history are lacking.

1 Gillison et al. JAMA 2012; 15(307): 693 – 703