Other Disease Caused by HPV

In addition to its role in the development of cervical cancer, HPV has been implicated in a number of other human diseases, both infectious and cancerous.

• Infection with oncogenic HPV types can cause other less common cancers such as anal, penile, vaginal, vulvar, and head and neck cancers (Burd 2003; Prendiville and Davies 2004b).
  
  
• Infection with low-risk HPV types can lead to the development of anogenital warts (von Krogh 2001) (Gross et al 1985) which are typically benign and treatable. In very rare cases, HPV infection of the larynx can cause recurrent respiratory papillomatosis (RRP) (Lee and Smith 2005).

Other cancer caused by HPV

In addition to its role in the development of cervical cancer, infection with oncogenic HPV types, in particular HPV 16, can also cause other cancers, such as anal, penile, vaginal and vulvar cancers (Bjorge et al 1997; Frisch et al 1997; Pow-Sang et al 2002) which are relatively infrequent in comparison with cervical cancer (Ferlay et al 2004). Oncogenic HPV may also be involved in some rare head and neck cancers, in particular cancers of the oral cavity, larynx, and nasal and paranasal regions (Chen et al 2005).

(Reference: Prendiville & Davies 2004b)

Anal cancer

In the US in 2005, it is estimated that about 3990 cases of anal cancer will occur (American Society of Cancer 2005a). Although the incidence of anal cancer is less well described in other countries, studies in Denmark, Sweden and the US indicate that the disease is becoming more common. This is thought to be due to multiple factors, such as an increase in the average number of lifetime sexual partners and younger age at sexual debut, which are known to increase the risk of HPV infection (American Society of Cancer 2005a; Burd 2003; Frisch et al 1997).

These and other risk factors for anal cancer are similar to those for cervical cancer and, like the cervix, the anal canal contains a transformation zone which can be infected by HPV, leading to the development of lesions (Cheonis 2001). HPV infection is regarded as a likely precursor to anal cancer, rather than as a necessary cause, as it is for cervical cancer (Gagne et al 2005; Walboomers et al 1999). A high prevalence of anal squamous intraepithelial lesions, precursors of anal cancer, have also been reported in sexually active men who have sex with men (MSM), which may reflect an ongoing exposure to HPV (Chin-Hong et al 2005).

Penile cancer

Penile cancer is a rare disease in North America and Europe, accounting for only 0.2% of cancers in men in the US (American Society of Cancer 2005b), but it is more common in parts of Africa, Asia and South America. In Brazil, for example, it is estimated that penile cancer accounts for 17% of all malignancies in men (Pow-Sang et al 2002). HPV and smoking seem to be risk factors in penile cancer, as is the presence of an intact foreskin, but the link between HPV and penile cancer is not as well established as that between HPV and cervical cancer due to a lack of studies (Pow-Sang et al 2002). As with cervical cancer, HPV 16 is commonly found in penile cancers (Salazar et al 2005).

Vaginal and vulvar cancers

In addition to its role in the development of cervical cancer, infection of the female genital tract with oncogenic HPV is associated with cancers of the vagina and vulva (American Cancer Society 2005b; American Cancer Society 2005a). In the US, vulvar cancer accounts for 4%, and vaginal cancer for 3% respectively of cancers of the female reproductive organs (American Cancer Society 2005b; American Cancer Society 2005a). It is estimated that 810 women in the US will die of vaginal cancer and 870 will die of vulvar cancer in 2005 (American Cancer Society 2005b; American Cancer Society 2005a). HPV 16 is thought to be important in the aetiology of these diseases, increasing the risk of developing vulvar and vaginal cancers by approximately 4.5 times. An association between HPV 18 infection and the development of pre-invasive lesions has also been shown (Bjorge et al 1997).

Infection with low-risk HPV types, such as HPV 6, 11, 40 and 44, can lead to the development of anogenital warts (Burd 2003; Muñoz et al 2003; von Krogh 2001). These can be present in four distinct clinical forms (Gross et al 1985; von Krogh 2001):

• Condyloma acuminata – soft, skin-coloured fleshy warts
• Flat condyloma-like lesions
• Pigmented papules – small, hard lesions, ranging in colour from pink to brown
• Lesions that are only seen when acetic acid is applied to them

HPV 6 and 11 are found in over 90% of anogenital warts (von Krogh 2001), and these types are rarely associated with oncogenesis in the cervix (Burd 2003; Muñoz et al 2003).

Anogenital warts are a common condition, affecting approximately 1% of the population of Europe and the US at any point in time (von Krogh 2001; Wilson 2001). The warts can appear several months after infection as either small white lumps or as larger, cauliflower-shaped growths (Prendiville and Davies 2004b). They can occur both externally and internally in the genital area. Although anogenital warts are caused by low-risk HPV types and therefore not associated with oncogenesis, they are nonetheless associated with psychological stress, which can have more impact than the morbidity due to the disease (Gall 2001).

Spontaneous resolution of anogenital warts occurs in 10-20% of cases (Prendiville and Davies 2004a) and there are a number of treatment options, although treatment choice depends on the morphology, number and distribution of the warts. Examples of the treatments available include:

• application of either salicylic acid tape (SFU), podophyllin or imiquimod
• cryotherapy
• surgical or laser removal
• ablation (can be self applied or applied by a doctor)
• excision by laser, knife or loop

Often, there may be recurrence of the warts following treatment. However, long-lasting remission or cure of warts and/or symptoms is possible (Prendiville and Davies 2004a; von Krogh 2001).

A potentially more serious, but much less common consequence of infection with low-risk HPV types is recurrent respiratory papillomatosis (RRP). This disease is characterised by recurrent benign epithelial growths (papillomas) throughout the epithelial tract, and occurs in both adults and children. Spontaneous regression occurs in the majority of cases, although surgical treatment is usually necessary to remove the associated lesions. Alternatively, anti-viral therapies such as α-interferon and cidofovir can help inhibit HPV replication and prevent the spread of the disease. RRP can develop as a result of HPV transmission from mother to child during childbirth.

(Reference: Prendiville & Davies 2004a)