HPV: Answering your worried patients's questions

April 1, 2007

Educating concerned patients that getting HPV is less about promiscuity and more about having sex with a new male partner can soften the stigma.

Educating concerned patients that getting HPV is less about promiscuity and more about having sex with a new male partner can soften the stigma. Here's expert advice for reassuring those who test HPV-positive that they most likely don't have cancer, their husbands aren't necessarily cheating, that it's just as easy to get rid of HPV as to get it-and more.

  

"I have WHAT?!!?"

"How did I get HPV? Who gave it to me?"

"Is my husband or boyfriend cheating on me?"

"What should I tell my husband? Should we use condoms from now on?"

"Can I re-infect my partner?" 1

How prepared are you to answer emotional questions such as those above when breaking the news to your patient that she has human papillomavirus?

Anxiety, anger, or self-depreciation will often drive her reaction. Critical to your patient counseling is understanding the natural history of HPV infections-including how it's acquired and viral transmission patterns. The psychological impact on women with genital warts or an abnormal Pap test or a positive HPV DNA test result isn't always as extreme as the reactions above-though that's what you'll hear most often. It will vary, ranging from "oh, that's part of life," to surprise, to major concern about past and future sexual relationships.

To be sure, testing HPV-positive often causes adverse psychological reactions based on a patient's fears that HPV is synonymous with cervical cancer. By recommending prophylactic vaccination to patients-but only after clearly explaining the natural history of HPV infection-clinicians can help pave the way for its acceptance.2

Our goal here is to review the current knowledge and understanding of HPV infection, emphasizing transmission, acquisition, and means of protection. Armed with that information, you'll have the answers to most of your patients' questions at your fingertips.

AN ANCIENT VIRUS

A relatively simple DNA virus, HPV has been around since prehistoric times. Though it's not likely to mutate, there are more than 100 known genotypes (types for short), about 40 of which preferentially infect the squamous epithelium of the anogenital and upper aerodigestive tracts.3 Transepithelial microfissures and erosions give viruses easier access to proliferating cells (Figure 1), whereas the immature squamous metaplastic cells in the cervical and anal transformation zones (TZ) expose themselves directly to the virus (Figure 2). These situations explain why the introitus and the immature TZ are favorable sites for HPV infection. Also, erosive or ulcerative lesions caused by herpes and chlamydia provide direct access to basal-type repair cells; this explains why infection by these two organisms increases the risk of developing HPV-related diseases.3

MODES OF TRANSMISSION

"How did I get HPV?"

HPV is transmitted by direct skin-to-skin contact, that is, between lesionalepithelium containing mature, potentially infectious virions (Figure 3) and the squamous epithelium of a susceptible host. Most genital HPV infections are transmitted by either sexual intercourse or "outercourse" (foreplay without intravaginal penetrating sex). In the case of intercourse, the entire epithelium of the lower genital tract can be infected, whereas in "outercourse" only the external vulvar area is at risk of infection.4 The virus may also be transmitted horizontally from one site to another by genital-digital manipulation. For example, the anal canal or the vagina may be infected by HPV from perianal and/or vulvar condylomata or intraepithelial neoplasia via fingers. Oral sex can cause heteroinoculation of the upper aerodigestive tract.3

Some HPV types seem to be transmitted more easily than others.

  • THE HIGH-RISK HPV TYPE 16 is the one genital HPV type that's most frequently transmitted and acquired. Present in 50% of all HPV-infected people, it tends to be linked with more numerous sexual partners than its other high-risk and low-risk counterparts.5
  • OF THE LOW-RISK HPV TYPES, type 6 has a much greater chance of being transmitted than, for example, type 11; HPV type 6 produces most genital warts.

"Who gave me HPV?"

The answer is: Either your patient's current-or more likely-one of her past sexual partners, particularly the most recent ones. There's only one clear-cut scenario implicating the current partner as the source of HPV: penile lesions and complete virginal status of the female partner prior to sexual debut. Without clearly identifiable lesions, evidence of HPV DNA of the same type (particularly if the woman has a less common type) in the male partner could also be construed as thebasis for transmission in the couple.

There's generally a poor correlation of HPV types in heterosexual couples.6 Indeed, HPV positivity and HPV type are often different in cervical and penile samples, mainly because a woman with cervical intraepithelial neoplasia (CIN) is a long-time HPV carrier, whereas the partner is likely to be a transient HPV carrier. In such cases, a different type of HPV detected in the male from that found in the cervical lesion of his wife or girlfriend might have been acquired from a previous partner before the current relationship began, and by inference, is irrelevant to the wife's (or current girlfriend's) developing a cervical lesion.

"Is HPV related to promiscuity?"

Not necessarily. Unlike most viral STIs, HPV is not confined to highly sexually active people who practice short-term "serial" monogamy. Rather, epidemiologic data suggest a high prevalence of HPV occurring in sexually "normal" individuals. As such, the virus' high transmissibility explains the high HPV prevalence. In this regard, HPVtransmissibility is comparable to bacterial rather than viral STIs.

In fact, HPV is the most common of all sexually-transmissible agents.7 Indeed, the rate of HPVperact transmission probability is much higher than HIV or herpes simplex virus, type 2 (HSV-2), both of which carry a probability of one in 1,000 acts. The medianperact transmissibility of HPV (as estimated by computer simulation studies on university students) is 40% per coital act. Moreover, the likelihood of male-to-female transmission reaches 100% with only 11 sexual encounters.8

The high probability of transmission is supported by the fact that despite the relatively short duration of HPV infection, it's very common in both sexes. Simulation studies of transmission dynamics have shown that HPV prevalence among male partners may be at least as high as that of women. Investigators using computer simulation models and HPV-16 seroprevalence data found a per partner male-to-female transmission probability of 60% to 80% for type HPV-16.9

"Is oral sex safe?"

Genito-oral HPV transmission in adults who lack visible lesions seems to be rare.4 On the other hand, orogenital transmission is possible in the presence ofclinically visible external lesions, and in fact, may be responsible for a fraction of cancers of the upper aerodigestive tract.

"Is it possible to contract HPV by nonsexual means?"

Although rare, there is circumstantial evidence for nonsexual transmission.10 Genital HPV types have been detected in the skin and fingernails of patients with external genital warts, which provides the biological basis for horizontal transmission.11 Perinatal "vertical" HPV transmission from mothers having vulvovaginal warts to their newborns has been shown by many epidemiologic studies.3 Fortunately, the risk for developing external lower genital tract lesions or juvenile onset of recurrent respiratory papillomatosis, or both, is very low (about seven per 1,000 pregnancies with warts). Typically, the lesions are produced by low-risk HPV type 6 and to a lesser extent, type 11.12

Whether transmission of HPV can occur via HPV-contaminated fomites such as underwear, surgical instruments, sex toys, etc., is unproven and is unlikely for HPV, which is by definition an obligatory intranuclear "parasite" incapable of surviving for any length of time outside of squamous cells.13

"Can my baby be infected in utero or while breastfeeding?"

HPV in semen may be transmitted through the ejaculate of men who have lesional epithelium in the distal urethra or glans of penis.14 Although there's no empirical evidence for this transmission route, this may have implications for sperm donors, as well. Thorough washing of sperm prior to intrauterine insemination likely provides HPV-free donated sperm. HPV is not transmitted via blood, for it is a purely epidermotropic virus, is not known to have a viraemic phase, and has not been found in blood. So far, HPV transmission to infants via breastfeeding hasn't been documented.

THE MOST COMMONLY ACQUIRED STI

Just how common is HPV infection? It is estimated that in the United States, 4.7 million sexually active individuals aged 15 to 24 will develop new high-risk HPV infections yearly.7 For all ages combined, the total burden of infections tops 6 million cases annually; the vast majority will be asymptomatic. The annual incidence, including low-risk types, is likely to be 30% to 50% higher. This number equals the combined frequency of infections by trichomoniasis, chlamydia, gonorrhea, syphilis, HSV-2, HIV, and hepatitis B. The lifetime risk of acquiring HPV, mostly before age 30, is 75%!15 Exceptions are couples engaged in lifelong, sexual monogamy since virginity.

The number of recent sexual partners is the most important risk factor for acquiring HPV infection. Next in importance are young age at first intercourse and a male partner's high-risk sexual behavior.5 Admittedly, acquisition and transmission of HPV are extremely common in sexually active individuals. These observations are clinically important, for acquiring HPV doesn't necessarily have to be equated to promiscuity, rather it has more to do with having sex with a new male partner.4,16 Recently, a second HPV peak, although considerably smaller (≤15%) than in adolescents, has been observed in postmenopausal women in certain countries in South America, Russia, etc.17 An impaired immune system's ability to clear HPV in these women and perhaps new infection by recent partners are likely responsible for this "second" increase in HPV prevalence in this cohort. Whether the findings are related to increased risk for developing cancer precursor lesions is to be investigated by long-term, prospective studies.

"Is my partner unfaithful?"

Not necessarily; he may have acquired HPV from earlier sexual partners and unknowingly become a carrier of subclinical lesions. This is why we advise practicing protected sex with consistent and appropriate use of condoms for at least the first 6 months of a new relationship to reduce the risk of acquiring HPV. Although an arbitrary time frame, it usually takes about 6 months to decide whether the new relationship will last. In the former case, mutual monogamy is likely and also, preexistent latent HPV or lesional epithelium-or both-have time to spontaneously clear.

"Is HPV forever?"

The good news is that as easy as it is to acquire HPV, it's equally easy to get rid of it, presumably for life. This is due to accrued immune response to the virus, and since immune memory is HPV type-specific, the individual is protected from being infected again by the same virus type. Some 90% of HPV infections are transient and clear within 3 years without a patient ever realizing she/he had the virus. In general, the younger the patient with HPV, the faster it clears. Most (60%–80%) new HPV infections clear within 1 year.3,16

Whether viral infection is completely cleared or remains confined within the epithelial basal cell layer (rendering it undetectable via methods that sample superficial layers) is an ongoing debate that will only be resolved by long-term follow-up of large epidemiologic cohort studies. Studies on women aged 30 years and older show low rates of latent HPV infection (0%–8%).3 This is mainly due to long-term, protective immune response acquired during earlier years and to mid-adult or older couples practicing monogamous sex. This is also true for those who develop low-grade squamous intraepithelial lesions or acuminate condylomata. The rate of spontaneous clearance of LSIL Pap in untreated adolescents is roughly 90% within 1 year.16

"Who's at risk for genital cancer?"

Focus on those with long-term, persistent, high-oncogenic risk HPV infections. Most of these patients are in their 30s and older and are at a substantial risk for developing lower genital tract (LGT) precancers and invasive cancers.3 The risk is more than 100-fold compared to HPV 16/18-negative individuals. By contrast, the average relative risk for smokers to develop lung cancer is only 10.3 The most common LGT cancers and their precursors occur in the cervix, where HPV types 16 and 18 cause about 70% of these lesions. Individuals harboring such infections are the ones who benefit the most from organized cancer screening programs including HPV DNA testing as an adjunct to or (as new evidence accrues) followed by Pap cytology. Ancillary risk factors in addition to age and high-risk HPV types, are impaired immunity including HIV infection and long-term oral contraception use plus smoking, history of HSV-2, chlamydia, and external genital warts.

"Should my partner use condoms from now on?"

Given the very high risk of transmitting HPV, it's important to stress that the condom reduces transmission risk only if it's used consistently and correctly.18 Unfortunately, regular use of condoms, in reality, is practiced only 75% of the time. Moreover, condoms that are used may be removed before penetration, or rupture/slip during intercourse. It's estimated that, due to the high sexual (and genital skin-to-skin) transmissibility of HPV, condoms may simply delay transmission by increasing the number of sexual acts from 11 to 24 before HPV transmission becomes a virtual certainty.8 Also, while latex condoms are impermeable to all sexually transmitted microorganisms, they don't cover the base of the penis. Admittedly, condoms are not the ultimate answer to curbing HPV infection. However, they're recommended for those in unstable or casual sexual relationships to reduce the risk of acquiring not only HPV but particularly other STIs such as chlamydia, gonorrhea, HIV, HSV-2, and hepatitis B virus.

"Should my partner be examined?"

Actually, the only time you need to examine an HPV-infected patient's male sexual partner is if he reports clinically visible lesions, such as penile or anal warts.19 The rationale is that the current partner is often free of evident disease and therefore may not be the source of the woman's infection. Even if he was, usually the lesion is subclinical, and most morphologically low-grade lesions clear spontaneously.20

In addition, examination at high magnification with 3% to 5% acetic acid solution often leads to overdiagnosing and overtreating benign HPV-unrelated penile skin conditions with potentially disastrous adverse events. It's sufficient to tell the worried female patient to use condoms consistently, at least until there's evidence that her lesional epithelium is cured. This may (at least theoretically) prevent re-infection from a partner who could be a carrier of HPV-related disease, since the repairing epithelium is made of highly replicating cells and the open wound provides direct access to the virus. But usually recurrence is not due to re-infection from the current partner, but to activation of latent HPV found in the epithelium near the previously treated area.2

"Can I infect my partner?"

Probably not-if the "donor" is the current partner-because HPV infection is type-specific. As a result, his immunogenic response should be specific to that particular HPV type. In other words, he's likely to be protected from being re-infected by the same type of HPV that he originally carried and transmitted. Realize, however, that there's no hard evidence for this concept.

It's a different story if her current partner is not the "donor" and is immunologically susceptible to becoming infected: he may either become an HPV carrier or de-velop lesional epithelium. However, for the vast majority, latent HPV is short-lived, and low-grade, subclinical, penile lesions spontaneously regress over time. If a patient's successfully treated HPV-related lesions recur, it won't be due to re-infection. It will stem, rather, from subsequent growth of tiny satellite lesions that escaped detection when the woman was first treated or else activation of latent HPV localized in the normal epithelium adjacent to treatment fields.21

"How can I avoid transmitting HPV?"

The only veritable and effective means to prevent HPV infection is to abstain from sexual contact-even "outercourse." Indeed, virgins without penetrative intercourse but contact with a partner's infected genital skin or semen-or both-may develop external genital warts.4

Short of abstaining from all sexual contact:

  • Lifelong, mutual, monogamy is the next best strategy for reducing risk.

Other means are:

  • Delaying sexual debut;
  • Limiting the number of sexual partners preferably to those who've either abstained for a long time or had only a few previous partners;
  • Consistent and correct use of condoms; and
  • Practicing sexual hygiene before and after each sexual encounter. Some refer to these preventive measures as the ABC approach-Abstain, Be faithful, and use Condoms.22

CONCLUSION

Educating women about how genital HPV is acquired and transmitted is key to both destigmatizing and preventing HPV infection. The even better news is the recent FDA approval of a prophylactic, quadrivalent HPV 6, 11, 16, and 18 recombinant vaccine (Gardasil). Another bivalent HPV 16/18 vaccine will likely soon be approved, as well (Cervarix). These vaccines can potentially markedly reduce the burden of disease andassociated costs. Multiple, large randomized clinical trials involving 15- to 26-year-old females showed that the approved vaccine had a 96% efficacy in preventing vaccine-containing HPV-type 6, 11, 16, and 18 persistent infections and was 100% effective in preventing their related cancer precursors and warts of the LGT.23

HPV's very high prevalence and transmissibility argue quite strongly for mass vaccination programs of not only presexual teens but also women who've already acquired HPV infection of one but not all vaccine-specific HPV types via "catch-up" vaccination. Obstetricians and gynecologists, therefore, can play a very important role in promoting and implementing universal, prophylactic HPV vaccination programs.

DR. FERENCY is Professor of Pathology and Obstetrics and Gynecology, The SMBD-JewishGeneral Hospital and McGill University, Montreal, Quebec, Canada.

DR. FRANCO is Director, Division of Cancer Epidemiology, and Professor, Departments of Oncologyand Epidemiology & Biostatistics, McGill University, Montreal, Quebec, Canada.

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