[Table of Contents]

Volume: 23S6 - November 1997

National Goals for the Prevention and Control of Sexually Transmitted Diseases in Canada
November 1997

Goals

Human Papilloma Virus

Drs. John W. Sellors and Alice Lytwyn

The prevalence of human papilloma virus (HPV) infection among women and men in Canada is unknown. American and European studies, using laboratory methods with varying sensitivities, have shown that from 10% to over 40% of sexually active women are infected by HPV at any one point in time. HPV-associated disease may be the most common viral sexually transmitted disease encountered in clinical practice in the U.S. It has been implicated in a number of diseases including cervical cancer and dysplasia, vaginal, vulvar and penile cancers, external genital condylomata, and respiratory papillomatosis; yet surprisingly little is known about its natural history.

Cancer of the cervix is the second most common cause of cancer death in women worldwide. Recent studies offer strong evidence that certain types of HPV cause over 95% of cancers of the uterine cervix. In Canada, four decades of screening for pre-neoplastic cervical lesions using the Pap smear has halved the incidence of invasive cervical cancer, reducing it to 10th place among the most common cancers in Canadian women. However, over the past two decades, the rate of decrease in this preventable disease has been declining.

Among specialized population groups in Canada, the incidence of invasive cervical cancer substantially exceeds the national average. Cervical cancer is the first and second most common female cancer in Saskatchewan Indians and Canadian Inuit, respectively. Women of low social economic means and recent immigrants from countries where cervical screening is not well developed are at high-risk for cervical cancer. Cervical cancer is more common and may be more aggressive in women infected with HIV.

Vaginal, vulvar, penile and anal cancers are relatively rare in Canada. Vaginal and vulvar cancers are more frequent in women who smoke and have a history of cervical dysplasia and cancer. Anal cancers appear to be on the increase. Homosexual men practising receptive anal intercourse, particularly those who are HIV-positive, are at high-risk for this malignancy.

The prevalence of external condylomata or genital warts is estimated to be 2% in young, sexually active Canadian women. The vast majority of cases are transmitted by sexual contact; however, occasionally transmission may occur via common skin warts, fomites or during delivery by infected mothers. External warts are distressing psychosexually and difficult to eradicate.

The incidence of recurrent respiratory papillomatosis in Canada is unknown. Its incidence in the U.S. is estimated to be 4/100,000 children and 1/100,000 adults. Patients are primarily children who are exposed during birth to HPV found in the birth canal and external warts; they often require multiple surgical procedures and mortality rates are high. Laryngeal papillomatosis may also occur in children from exposure at the time of birth.

Screening and diagnosis

The Canadian Task Force on the Periodic Health Examination (1995) has stated that there is not enough evidence to recommend HPV screening of asymptomatic women. HPV testing has been technically difficult, and even when identified does not necessarily predict disease. Only a proportion of individuals exposed to HPV acquire the infection and only a minority of them develop clinical disease. When clinical disease does not occur, a proportion of people are able to clear non- and precancerous lesions spontaneously. Susceptibility factors are being studied and include HPV type, viral load, persistence of infection, human leukocyte antigen type, cell-mediated response, drug- or disease-induced immunosuppression. The effects of smoking , parity and co-infection with other STDs remain controversial.

Increasingly, commercial kits are becoming available, with and without nucleic acid amplification. Newer assays are able to detect more oncogenic types of HPV and quantitative assays may offer increased specificity.

One strategy that may be useful is to link HPV screening with Pap smears. However, it will be important to recognize that there will be a need to shift resources. To do so, it might be wise to recognize that some women are vastly over-screened and others are under-screened with Pap smears, and resources and guidelines should be revised and followed as appropriate. It is also important to recognize that, as yet, there isn't enough known about HPV to set definite guidelines.

Self-testing for HPV infection is becoming an attractive alternative to Pap smears. The necessity for a pelvic examination prevents some women from complying with Pap smear screening. Specimens for HPV testing, on the other hand, can be self obtained through vaginal swabs, vulvar wipes and urine samples. In the future, if such a method can be shown to have acceptable sensitivity and specificity, it could be used either alone or as a step down to Pap smear in areas where barriers to conventional Pap smear screening exist.

HPV testing may be most useful in the management of women who are diagnosed as having low-grade squamous intra-epithelial lesions on Pap smear. Fifteen to 20% of these women have an underlying high-grade cervical lesion. It is postulated that testing for oncogenic HPV-DNA could be used as an alternative to repeat Pap smear and to colposcopy for identifying those women who are harboring a high-grade lesion. Two Canadian randomized controlled trials are currently under way to examine this issue.

Screening high-risk groups for anal carcinoma has been suggested, and is being investigated in HIV-seropositive men. Anoscopy and exfoliative cytology are being used to identify premalignant anal lesions. Improved screening for anal epithelial lesions in this high-risk group should be a research priority.

Control strategies

There is currently no direct treatment of HPV, only its sequelae. Pap smear screening of cervical cancer, along with treatment, has been successful in decreasing the incidence of cervical cancer, the most common malignancy induced by HPV. Treatment of anogenital dysplastic lesions, particularly those of the cervix and anus, is ablation or resection. Treatment of cervical dysplasia is associated with over 90% success rate. Treatment and follow-up of low-grade lesions remain controversial and new guidelines in this area are needed. Treatments for genital warts include antimitotics (podophyllum; podophyllous home treatment), physically-destructive agents and procedures (liquid nitrogen, trichloroacetic acid, electrocautery, laser vaporization), and surgical excision. These treatments usually require multiple visits; side effects are common and latent infection by HPV usually persists in surrounding tissues. Recurrence rates range from 10% to 40%. A new topical immune modulator, imiquimod, stimulates the production of interferon-alpha and other cytokines and has been shown to be effective in eliminating genital warts; however, follow-up is limited and long-term recurrence rates need to be determined.

Barrier contraceptives, which have been successful in reducing transmission of most sexually transmitted diseases, do not appear to be effective in preventing HPV infection. Vaccines against HPV infection are being developed, and early clinical trials are in progress.  Preliminary trials of the vaccine in women with invasive cervical cancer have demonstrated that the vaccine elicits antibody production, but more definitive study is needed. Another promising avenue of research is the development of spermicidal agents effective against this virus.

If the focus of research and prevention is on oncogenic strains of HPV, it may be important to also investigate circumcision as a method of reducing cancer of the cervix.

Surveillance needs

To make any significant progress in the control of HPV-related disease we need to determine HPV prevalence in the general population and high-risk groups, including the prevalence of latent, subclinical and overt infection at all sites. We need to collect baseline information on rates of respiratory and laryngeal papillomatosis (see Table 4). The first step towards this would be the establishment of registries. The U.S. has recently established such a registry.

TABLE 4 Canadian Goals for Human Papilloma Virus By the year 2000:

• Determine the prevalence of HPV in Canada in the general population and among high-risk groups including Aboriginal peoples, recent immigrants and HIV-seropositive individuals
• Monitor mortality data on anogenital disease involving the cervix, vagina, vulva, anus and penis
• Determine the prevalence and incidence of laryngeal and respiratory papillomatosis

Numerous professional and provincial Canadian organizations are working on issues in cervical screening. In 1995, Health Canada convened several working groups, including the Cervical Cancer Prevention Network, to establish liaisons with provincial representatives and to formulate recommendations for decreasing the incidence of cervical cancer in Canada. Working in collaboration with the Cervical Cancer Prevention Network is indicated. This network is working on the standardization of nomenclature across Canada and the development of a registry to provide data to assist in developing future policy and identifying areas for research.

[Previous] [Table of Contents] [Next]