The Canadian Journal of Human Sexuality

Volume 6 - Number 2 1997
Special Issue: STDs and Sexual/Reproductive Health

Published by SIECCAN
The Sex Information & Education Council of Canada

Sexually Transmitted Human Papillomaviruses: Current Concepts and Control Issues

Alice Lytwyn
Department of Pathology
Women's College Hospital
University of Toronto
Toronto, Ontario

John W. Sellors
Health Services Delivery Research Unit
Father Sean O'Sullivan Research Centre
McMaster University
Hamilton, Ontario

Abstract:

Sexually transmitted human papillomaviruses (HPV) are associated with condylomatous, dysplastic and malignant lesions of the cervix, vagina, vulva, anus, and external genitalia. Susceptibility to HPV and disease development are determined by HPV type, viral load, viral persistence, and immune status. This paper reviews current HPV concepts and control issues including the epidemiology, burden of infection, prevention, testing, and treatment of HPV. Goals for HPV control in Canada include determining and monitoring the prevalence of HPV infection, decreasing the incidence of HPV-associated diseases, and promoting HPV targeted basic science and clinical research. The development of vaccines holds promise for preventing the transmission and acquisition of this viral STD.

Key words:

• Human papillomavirus, Cervical cancer, HPV control strategies, HPV testing, HPV treatment

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Correspondence concerning this paper should be addressed to Alice Lytwyn, MDCM, FRCPC, Women's College Hospital, Department of Pathology, 76 Grenville Street, Toronto, Ontario, Canada M5S 1B2. Tel: (416) 323-6140.

Introduction

Sexually transmitted human papillomaviruses (HPV) are implicated in the pathogenesis of a number of anogenital diseases ranging from external genital warts to cancers of the uterine cervix and anus (Birley, Hart, Stacey, 1995; Bosch et al., 1995; Ferenczy, 1995a; Franco, 1995; Kiviat & Koutsky, 1993; Kurman, 1994; Mayeaux, Harper, Barksdale, Pope, 1995; Maymon et al., 1994; Palefsky, 1995; Palefsky & Holly, 1995; Schiffman, 1995; Schiffman et al., 1993; Stone, 1995; Woolley, 1995). Genital papillomaviruses have been linked, as well, to recurrent respiratory papillomatosis through vertical transmission during delivery (Corbitt, Zarod, Arrand, Longson, Farrington, 1988; Derkay, 1995; Pou et al., 1995). This paper reviews current concepts in genital HPV associated diseases, disease prevention, viral testing, and treatment. Health Canada goals and strategies for the control of human papillomavirus infection are presented.

Current Situation

Diseases Caused by Human Papillomaviruses

There are more than seventy types of human papillomaviruses, and of these, over twenty infect mucosal tissue and can be sexually transmitted (Stoler, 1996). Human papillomaviruses are implicated in the pathogenesis of cancer of the uterine cervix, which is the second most common cause of cancer and cancer death in women worldwide, with 80% of cases occurring in the developing world (Schiffman, 1993; Sherris, Wells, Tsu, Bishop, 1993). Invasive squamous cervical cancer is preceded by preneoplastic lesions that can be identified on Papanicolaou (Pap) smear and subsequently treated. The strategy of screening for these precursor lesions has been associated with a 90% reduction of cervical cancer incidence in some Western countries (IARC, 1986; Sherris et al., 1993). Recent molecular and epidemiologic studies offer strong evidence that over 95% of cancers of the uterine cervix are caused by certain types of human papillomaviruses (Franco, 1994). Over twenty of these "oncogenic" or cancer associated types of HPV have been identified; the most common are types 16 and 18 (Bosch et al., 1995; Franco, 1995; Kiviat & Koutsky, 1993; Palefsky & Holly, 1995; Schiffman, 1995; Schiffman et al., 1993). These viruses are able to integrate into the human genome, and by a variety of mechanisms including viral protein production and binding of human suppressor p53 and retinoblastoma proteins, lead to unregulated cell growth, accumulation of chromosomal mutations, and finally to malignant transformation (Birley et al., 1995; Herrington, 1995; Palefsky & Holly 1995). Oncogenic HPV sequences have been identified in the immediate cervical cancer precursors known as high grade squamous intraepithelial lesions (HSIL), or cervical intraepithelial neoplasia (CIN) 2 and 3 (Bavin et al., 1992; Koutsky et al., 1992; Lungu et al., 1992; Smits et al., 1995). The so-called low grade cervical lesions, that is CIN 1 and flat condyloma (soft, wartlike growths), also carry HPV sequences, however, many of the types identified have been the "low risk" viruses, most commonly 6 and 11 (Kurman, 1994; Lungu et al., 1992). Most warts on the cervix are termed "flat" condylomata and are best visualized with a colposcope after the application of 3-5% acetic acid. Some low grade cervical lesions may be caused by oncogenic HPV, and only these appear to have the potential of progressing through CIN 2 and 3 and to invasive cancer (Campion, McCance, Cuzick, Singer, 1986; Herrington et al., 1995; Sherris et al., 1993; Syrjanen, 1995; Woodman et al., 1996).

Adenocarcinoma of the cervix, although less common than squamous cervical cancer, is also associated with oncogenic HPV, most notably type 18 (Bosch et al., 1995). HPV-DNA has also been identified in other anogenital invasive cancers and their precursors; these include squamous cancers originating in the vulva, vagina, anus and penis (Kurman, 1994; Mayeaux, Harper, Barksdale, & Pope, 1995; Maymon et al., 1995; Palefsky, 1995).

External genital warts of the vulva, penis and anal canal are caused by infection with low risk human papillomaviruses (Birley et al., 1995; Ferenczy, 1995a; Stone, 1995; Woolley, 1995). These are not malignant lesions; however, they constitute an important medical problem because they are common, may be difficult to treat, and tend to recur.

Recurrent respiratory papillomatosis is primarily a disease of children in whom numerous papillomas occur in the upper aerodigestive tract, including the larynx and vocal cords. The papillomas commonly cause hoarseness, and obstructing papillomas may result in respiratory distress. High and low risk HPV-DNA sequences have been identified in the papillomas. While the viruses associated with respiratory papillomatosis are not acquired through sexual activity, they are nevertheless likely genital in origin, acquired during delivery (Corbitt, Zarod, Arrand, Longson, & Farrington, 1988; Derkay, 1995; Pou et al., 1995).

Transmission of Human Papillomavirus Infection

Anogenital human papillomavirus infection is primarily transmitted by sexual contact (Ellen, Moscicki, & Shafer, 1994; Ferenczy, 1995a; Palefsky & Holly, 1995; Schiffman et al., 1993), although in a minority of cases there appear to be additional, or alternative, routes of transmission. Some evidence, although controversial, suggests that rare cervical and penile infections may be acquired during delivery through exposure to HPV present in the maternal birth canal or external warts (Cason, 1996; Roman & Fife, 1986). Laryngeal papillomatosis is believed to be acquired in this way (Derkay, 1995). Some external anogenital warts may be acquired perinatally during delivery as well, or may result from contact with common skin warts and fomites (Ferenczy, 1995a).

Permissive Factors for HPV Infection and Development of Clinical Disease

Of individuals exposed to HPV, only some will be infected, and only a minority will develop clinical disease (Table 1). Analyses of cervicovaginal specimens from sexually active women have found that over 40% are positive for HPV-DNA, and up to 10% are positive for the oncogenic viruses (Bauer et al., 1991; Bishop, Sherris, & Tsu, 1995; De Villiers et al., 1992; Ellen, Moscicki, & Shafer, 1994; Ferenczy, 1995b; Reid & Lorincz, 1991; Van Den Brule, Walboomers, Du Maine, Kenemans, & Meijer, 1991). In contrast, the prevalence of low grade cervical lesions in the general population is approximately 5% (Kurman, Henson, Herbst, Noller, & Schiffman, 1994; Slawson, Bennett, & Herman, 1993), that of high grade lesions 2% (Cruickshank & Kitchener, 1996), and that of external genital warts 2% (Ferenczy, 1995a; Sellors et al., 1992). When clinical disease does develop, a proportion of patients are able to clear the non- and precancerous lesions spontaneously (Syrjanen, 1995). Similarly, respirtory papillomatosis is estimated to develop in only 1 out of 400 children delivered vaginally of mothers with external genital warts (Derkay, 1995). It is clear that factors in addition to HPV exposure must be present to either allow, or inhibit, infection and disease development (Table 2).

It has long been observed that certain tissues and organs are more resistant to disease than others. For example, vaginal, vulvar and penile cancers are uncommon and usually occur later in life than cervical cancer (Kurman, 1994; Maymon et al., 1994). However, personal susceptibility is an important factor for these malignancies, since vaginal and vulvar cancers occur more frequently in women who already have a history of cervical dysplasia and cancer (Kurman, 1994).

Susceptibility factors include HPV type, viral load, persistence of infection, HLA type, cell mediated response, and drug or disease induced immunosuppression, including infection with human immunodeficiency virus (HIV) (Apple et al., 1994; Arends et al., 1997; Bosch et al., 1995; Brisson et al., 1996; Campion, McCance, Cuzick, & Singer, 1986; Euvrard et al., 1997; Ferenczy, 1995a; Franco, 1995; Herrington, 1995; Herrington et al., 1995; Hildesheim et al., 1994; Ho et al., 1993; Koutsky et al., 1992; Mehal et al., 1994; Northfelt, 1994; Palefsky, 1991; Palefsky & Holly, 1995; Schiffman, 1995; Sherris et al., 1993; Syrjanen, 1995; Woodman et al., 1996). The associations with smoking, parity, and evidence of previous infection with other sexually transmitted pathogens, such as Herpes simplex virus and Chlamydia trachomatis, remain controversial (Ellen et al., 1994; Palefsky & Holly; Schiffman et al., 1993).

Burden of HPV Infection

Worldwide, and particularly in developing countries, the burden imposed by cancer of the uterine cervix is high. In Canada, while four decades of screening for preneoplastic cervical lesions have coincided with a 50% decrease in the incidence of invasive cervical cancer and its reduction from first to tenth place among the most common cancers in Canadian women, it is of concern that the past two decades have seen a decline in the rate of decrease in this preventable disease (Hankins, Lamont, & Handley, 1994; Parboosingh et al., 1996). As well, among some 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 (Hankins et al., 1994). Women of low socio-economic means and recent immigrants from countries where cervical screening is not well developed are at high risk for cervical cancer (Parboosingh et al., 1996). Cervical cancer is more common and may be more aggressive in women infected with HIV (Maiman, 1994; Northfelt, 1994; Palefsky, 1991).

It is estimated that there will have been 1350 new cases and 390 deaths from cervical cancer in Canada in 1996 (Parboosingh et al., 1996). In 1991, the economic cost for treating and managing invasive cervical cancer was approximately $180 million to $270 million (Miller et al., 1991). Treating preneoplastic cervical lesions is costly, as specialized colposcopy services and trained personnel are required. The annual cost of colposcopy and treatment is estimated to be $6 billion in the United States (Kurman et al., 1994). It has been estimated that approximately $30 million per year is spent in the province of Ontario for screening and follow-up activities (OMA, 1993). The problem of treatment is compounded by the uncertainty over the management of low grade cervical lesions. While ablation or resection is recommended for all high grade lesions, low grade lesions are variably followed or treated, and the most effective and efficient management remains to be established (Brotzman & Julian, 1996; Cruickshank & Kitchener, 1996; Kurman et al., 1994; Miller et al., 1991; Jones, Noller, Reid, Richart, 1994). Vaginal, vulvar and penile cancers are relatively rare in Canada; however, their management is associated with significant personal and economic costs.

External warts are estimated to have a prevalence of 2% among young sexually active Canadian women(Sellors et al., 1992). External warts are important because they are a nuisance (psychosexually and cosmetically) for the patient and his/her sexual partner, and are difficult to eradicate. Current treatment regimens report 10% to 40% recurrence rates (Sellors & Law, 1994). Treatments include antimitotics (podophyllum resin - physician applied; podofilox - home treatment), physically destructive agents (liquid nitrogen, trichloroacetic acid, electrocautery, laser vaporization), and surgical excision. Treatment usually requires multiple visits and side effects are common, ranging from skin irritation to systemic toxicity (Ferenczy, 1995a; Heaton, 1995; Mayeaux et al., 1995; Maymon et al., 1994; Sellors, 1995; Sellors & Law, 1994; Stone, 1995; Woolley, 1995).

Anal cancer has an incidence of 7/1,000,000 men and 9/1,000,000 women in the United States (Table 1), and is increasing at a rate of approximately 2% per year. Homosexual men practising receptive anal intercourse, particularly those who are HIV positive, are at high risk for this malignancy. It is estimated that the rate of anal cancer in HIV positive men is similar to the rate of cervical cancer in women prior to the institution of cervical screening (Palefsky, 1994; Palefsky, 1995; Ramanujam, Venkatesh, Barnett, & Fietz, 1996).

Respiratory papillomatosis has an estimated incidence of 4 / 100,000 children and 1 /100,000 adults in the United States (Table 1). This is a rare but significant disease, because patient morbidity is high. The patients are primarily children and they often require multiple surgical procedures for treatment and palliation (Derkay, 1995). Laryngeal cancer has been documented in a number of patients with respiratory papillomatosis, and is also likely related to the HPV infection (Corbitt, Zarod, Arrand, Longson, & Farrington, 1988; Hartley, Hamilton, Birzgalis, & Farrington, 1994; Pou et al., 1995).

While rates of malignant diseases associated with HPV are documented in Canada, the prevalence of HPV infection among women and men in Canada is not known. American and European studies, using laboratory methods with varying sensitivities, have shown that from 10% to over 40% of sexually active women in the United States and European countries are infected by HPV at any one time (Bauer et al., 1991; Bishop et al., 1995; De Villiers et al., 1992; Ellen et al., 1994; Ferenczy 1995b; Reid & Lorincz, 1991; Van Den Brule, Walboomers, Du Maine, Kenemans, & Meijer, 1991).

Prevention, Testing, Treatment, and Patient Counselling

Prevention of HPV Infection

Successful, established disease prevention strategies have been limited to screening for, and treating, cervical squamous cancer precursors, thereby resulting in a decreased incidence of the most common malignancy induced by HPV. However, there are no comparable strategies to prevent HPV infection itself. Treating clinical lesions induced by HPV is assumed to decrease the reservoir of transmissible virus; however, it does not eliminate the potential for infection, as latent HPV infection may persist in the surrounding normal appearing tissues (Ferenczy, Mitao, Nagai, Silverstein, & Crum, 1985). Barrier contraceptives, which have been successful in reducing transmission of many sexually transmitted diseases, do not appear to be effective in preventing HPV infection (Ferenczy, 1995a), and as a result, there is a recent call for research into the development of spermicidal agents effective against this virus (Sokal & Hermonat, 1995). Vaccines are a promising strategy for prevention of HPV infection. Vaccines against HPV are being developed, and early clinical trials are in progress. The vaccines have elicited antibody production in women who have invasive cervical cancer (Borysiewicz et al., 1996; Frazer, 1996). Stabilization and regression of disease has occurred in two of these patients (Borysiewicz et al., 1996), and although the number of patients is too small for meaningful interpretation, the vaccine appears promising. Vaccine trials in women with pre-invasive cervical disease are also underway (McNeil, 1997).

Testing for HPV Infection

Studies exploring the potenial clinical role of testing for HPV infection have primarily centred on its use in cervical cancer and cervical preneoplasia screening and management. Pap smear screening at repeated intervals can potentially result in a 90% reduction in the incidence of cervical cancer (IARC, 1986). However, during any one time use, Pap smear sensitivity for detecting CIN/ cancer is reported to range from 20%-70% (Bavin et al., 1992; Carlson & Twiggs, 1992; Cuzick et al., 1995; Ferenczy, 1995b; Koss, 1993; Solomon, 1993). This raises concerns for missing significant lesions in women who may not be compliant with repeated screening, and also for those women whose missed lesion may progress to invasive cancer between screening intervals. Alternative or adjunctive screening methods, including testing for cervicovaginal HPV, may therefore be useful (Bavin et al., 1992; Cuzick et al., 1995).

The detection of oncogenic HPV in cervicovaginal samples correlates with the concurrent and future presence of CIN. However, several problems must be resolved before screening with HPV testing can be advocated. Many HPV-positive women, particularly those who are young, will either have no lesion or a low grade lesion; many of the latter will regress spontaneously. It is not yet clear how to identify those women whose low grade lesions either need, or will require, treatment. HPV testing has been technically difficult but, increasingly, commercial kits are becoming available with and without nucleic acid amplification. The ability to detect more oncogenic types of HPV and give a quantitative result may offer increased specificity, since it appears that highly reproductive infections have worse prognosis. Further complicating test interpretation is the fact that infected individuals may not shed HPV consistently. After reviewing the literature, the Canadian Task Force on the Periodic Health Examination concluded in its 1995 Update that the use of HPV detection methods to screen asymptomatic women could not be recommended at that time (Bauer et al., 1991; Bavin et al., 1992; Carlson & Twiggs, 1992; Cox, Schiffman, Winzelberg, & Patterson, 1995; Ellen et al., 1994; Ho et al., 1995; Johnson, 1995; Moscicki, Palefsky, Smith, Siboshski, & Schoolnik, 1993; Remmink et al., 1995; Schneider, 1996; Schneider, Kirchhoff, Meinhardt, &Gissmann, 1992; Zazove et al., 1993).

If the preceding problems can be resolved, HPV testing will be able to offer a unique advantage to Pap smear screening in that samples can potentially be collected without the need for a speculum examination. The fact that the Pap smear necessitates a pelvic examination prevents some women from participating in screening (Brownstein, Cheal, Achermann, Bassford, & Campos-Outcalt, 1992; Coyne, Hohman, & Levinson, 1992; Naish, Brown, & Denton, 1994). Specimens for HPV testing, on the other hand, can be self-obtained through vaginal swabs, vulvar wipes and urine samples (Coutlee et al., 1997; Fairley et al., 1992; Mahony, Luinstra, & Chong, 1995; Morrison, Goldberg, Hagan, Kadish, & Burk, 1992; Moscicki, 1993; Sellors et al., 1997; Vossler, Forbes, & Adelson, 1995). 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.

In addition to screening, HPV testing may be useful in the management of women who are diagnosed as having a low grade lesion, either ASCUS (atypical squamous cells of unknown significance) or LSIL (low grade squamous intraepithelial lesion: this encompasses CIN 1 and flat condyloma) on Pap smear. Fifteen to twenty percent of these women have an underlying high grade cervical lesion (Ferenczy, 1994; Richart & Wright, 1993; Sheets & Crum, 1994; Jones, Noller, Reid, & Richart, 1994). 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 harbouring a high grade lesion (Bavin, Giles, & Deery, 1993; Cox et al., 1992, 1995; Ferenczy, 1995b; Wright, Sun, & Koulos, 1995). Two Canadian randomized controlled trials are currently under way examining this issue (Lytwyn, Sellors, & Gafni, 1995; Sellors, Lytwyn, & Gafni, 1995).

Cervical HPV tesing may also be useful in identifying and managing cervical neoplasia in women who are immunodeficient because of infection with HIV or because of immunosuppressive therapy secondary to organ transplantation, for example. Cervical cancer appears to occur more frequently in HIV infected women, and indeed, the Center for Disease Control and Prevention in the United States has identified cervical cancer as an indicator disease for Acquired Immune Deficiency Syndrome (AIDS) (Castro, 1992). As expected, cervical dysplasia is more frequent in HIV infected women, and it also may behave more aggressively in these women (Maiman, 1994; Northfelt, 1994; Palefsky, 1991). In Canada, a nationwide multicentre study is investigating the use of HPV cervicovaginal testing in HIV positive women (Hankins & Lapointe, 1996). Table 3 lists the ways in which testing for HPV may be proven to be useful in the future.

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 (Northfelt, 1994; Palefsky, 1991, 1994).

Immune Response to HPV Infection

Recently, sensitive assays for antibodies to HPV proteins have been developed (Galloway, 1994). Some studies suggest that presence of serum antibodies correlates with persistence of HPV infection, and may therefore be used to identify those women at risk for clinical lesions (Wideroff, Schiffman, Nonnenmacher, Hubbert, Kirnbauer, Greer, Lowy, Lorincz, Manos, Glass, et al., 1995).

Cell mediated immunity and the HLA system may play key roles in preventing or facilitating chronic HPV infection. Currently, these are areas of intense research activity, and it is expected that the function of the immune system with regards to HPV infection and disease development will be better understood and elucidated in the next few years (McDougall, Galloway, & Daling, 1996; Rader, 1996).

Treatment

Present 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 (Bishop et al., 1995; Ferenczy, Choudroun, & Arseneau, 1996). There is no comparably effective pharmacological therapy.

External genital warts are primarily treated pharmacologically because the required surgical resection would be too extensive. Nevertheless, current drug therapies have limited success in eradicating the condylomas, and new drugs are under development. One such drug is Imiquimod, a topical immune modulator that stimulates the production of interferon-alpha and other cytokines. It has been reported to be effective in eliminating genital warts (Roy et al., 1996), however, follow-up is limited and long term recurrence rates need to be determined.

Patient Counselling

Health care workers, particularly those at STD clinics, frequently treat patients with genital warts or HPV-related abnormal Pap smears. In addition to the appropriate medical treatment, these patients often require psychosexual counselling. Patients with genital warts may consider them both distasteful and disfiguring. Studies indicate that the diagnosis may have a negative impact on sexuality, mood, social life, and emotional relationship with partners (von Krogh, Gross & Barrasso, 1997). A survey of women with recurrent HPV infection found that in the year following diagnosis, 86% had difficulty approaching new partners, 70% had feelings of isolation, 72% reported a reduced frequency of sexual contact, and 68% reported enjoying sex less. Over two-thirds reported feelings of anger, shame, or depression (American Health Association, 1993). As a result, there are a number of issues thatoften need to be discussed with patients (Sellors & Law, 1994).

It is important to dispel potential misconceptions that patients may have about HPV. For example, many patients will need, and be comforted by, information about the high prevalence of HPV, the generally benign natural history of most HPV infections, and the relatively low risk of subsequent genital cancer if management guidelines are followed. Many patients will assume that they have acquired HPV from their current sexual partner. While this may be the case, patients should be informed that due to the sometimes very long incubation time before lesions appear, the presence of HPV does not necessarily imply that the infection was acquired from the current partner or that the partner has been unfaithful. Although there is a high probability that the current partner is also infected, there is no proven benefit from examining partners.

Because infection with HPV may be concurrent with other STDs, testing for other sexually transmitted infections may be considered. Although condoms do not have a demonstrated effectiveness in preventing HPV transmission, patients with new sexual partners should be advised to use condoms at least until the treatment and control of genital warts has been completed, and that condoms should be used to protect against other STDs in the future (Gross, von Krogh, & Barrasso, 1997).

Smoking has been identified as a risk factor for the progression of infection with oncogenic HPV types to cervical preneoplasia and cancer (Kataja, 1992). As a result, patients with HPV who are current smokers should be advised to quit.

The appropriate counselling of patients with HPV by health care providers can have a significant positive impact. Raising and discussing the issues of concern that patients will likely have, and reassuring them that HPV is ultimately manageable, should be a natural part of the communication with patients during clinical evaluation procedures.

Organizational Activities

Organized activities for the control of HPV-induced diseases are primarily concerned with cervical cancer prevention, and in Canada these activities are represented by various medical, provincial and national committees. 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. Work is ongoing, and it is expected that recommendations and guidelines will be available in the near future (Parboosingh, 1996).

Information on respiratory papillomatosis is being organized into a national registry in the United States. The registry follows as a result of a 1995 task force that was convened to obtain data on the incidence, demographics, and treatment of recurrent respiratory papillomatosis (Derkay, 1995).

Goals for Control of HPV Infection

Human papillomavirus infection is unique among sexually transmitted diseases in that there is no present way to either prevent infection or to eradicate the responsible organism. On the other hand, some manifestations of the infection, primarily the dysplastic and condylomatous lesions, can be prevented, detected, treated and controlled with some success. Research targeted at human papillomavirus at the basic, epidemiological, and clinical science levels is needed.

Because we do not know the extent of the infectious pool that exists in Canada, it would be reasonable to identify the determination of HPV prevalence as a priority. These prevalence rates could then be used to monitor the effect of control initiatives. The HPV control goals, which form part of the proposed STD Control Goals for Canada, are summarized in Table 4.

Conclusion

Human papillomavirus infection is a common sexually transmitted disease associated with significant morbidity as well as increased risk of death. The goals put forward by Health Canada provide a framework for work in the area of HPV infection. It is anticipated that these goals will result in measurable control o this viral infection and its associated diseases.

Table 1 - Rates of HPV Infection and Associated Diseases

Disease	Prevalence
HPV anogenital infection in women
all anogenital HPV types	>40 / 100
oncogenic HPV types	10 / 100
Cervical neoplasia
low grade	5 / 100
high grade	2 / 100
External genital warts	2 / 100
	Incidence
Anal cancer
men	7 / 1 000 000
women	9 / 1 000 000
Recurrent respiratory papillomatosis
children	4 / 100 000
adults	1 / 100 000

Table 2 - Putative Permissive Factors for Human Papillomavirus Infection and Disease Development

Tissue site HPV associated: virus type, load, persistence Immune status: cell mediated immunity, HLA type, drug and disease induced immunosuppression Other, inconsistent association: previous or co-infection with sexually transmitted diseases, parity, smoking

Table 3 - Potential Uses of HPV Testing in Cervical Neoplasia

Screening for cervical neoplasia by identifying oncogenic HPV in: Cervicovaginal specimens Self collected vaginal, vulvar, urine samples Management of low grade cervical lesions: determination of triage to colposcopy, treatment, or observation Identification and management of cervical dysplasia in women infected with human immunodeficiency virus

Table 4 - Health Canada Goals for HPV Infection

Goals Determine the prevalence of HPV in Canada in the general population and among high risk groups including Aboriginal people, recent immigrants and HIV seropositive individuals. Repeat prevalence studies in 2005 and 2010. Monitor mortality data on anogenital disease involving the cervix, vagina, vulva, anus and penis. Determine the prevalence and incidence of laryngeal papillomatosis. Repeat prevalence studies in 2005 and 2010

Goals for Diseases Caused by HPV Decrease the incidence of invasive cervical cancer. Decrease the incidence of anal squamous cancer in high risk groups.

Surveillance Needs and Goals Determine HPV prevalence in the general population and high risk groups including prevalence of latent infection, subclinical infection and anogenital lesions. Monitor the incidence, prevalence and mortality anogenital disease of the cervix, vagina, vulva, penis and anus laryngeal papillomatosis.

Research Needs and Goals Promote research in academia and industry to improve screening and to include social science and behavioural components design and evaluate sensitive and specific assays to be performed on appropriate clinical specimens to enable collection of meaningful Canadian epidemiological data assessment of appropriate intervals for screening people at increased risk of anal cancer. Evaluate appropriate guidelines for the treatment of low grade lesions. Develop a vaccine for HPV. Development of effective barrier methods. Development of topical agents against HPV since current barrier contraceptives may not be effective to prevent the transmission of HPV. Investigate the factors which determine the establishment of HPV infection, the development of clinical disease, resistance and persistence.

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