9 Human papillomavirus (HPV)

9.2 Clinical features

9.2.1 Infection

Infection results from skin-to-skin contact, predominantly sexual, with a person with HPV infection. Transmission in the genital region may occur even when condoms are used and does not necessarily require penetrative intercourse. HPV may also be transmitted perinatally, from mother to newborn baby.

Clinically apparent warts are probably more infectious than subclinical infection. The virus penetrates micro-abrasions in the epithelium to reach the basal epithelial cells, where it causes the infected cells to produce proteins that delay cellular maturation. Continued replication of these infected cells in the intermediate epithelial layer, followed by virus replication in the superficial epithelial layer, results in the cellular overgrowth typical of warts.

For most people, HPV infection is transient and becomes undetectable by DNA testing within 6 to 12 months, but in some cases, HPV infection remains latent and may reactivate years later. As it is difficult to detect HPV in its latent stage, it is impossible to know whether in some cases the immune system can completely clear the virus or whether the virus remains latent at undetectable levels, capable of re-emerging later on.

Acquisition of HPV

Infection with oncogenic serotypes of HPV is common, with an estimated 70–80 percent of sexually active individuals becoming infected at some stage during their life. Initial infection occurs close to the time of sexual debut. In contrast to women, for whom the risk for HPV acquisition increases with age through the early 20s and then decreases, studies have demonstrated that incidence among men is relatively constant over a wide age range.4

Most episodes of infection become undetectable by DNA testing within two years of acquisition; the average duration of infection is one year. Previous infection does not necessarily create long-term immune memory so does not prevent future re-infection with the same HPV type.

At any one time, approximately 10 percent of women have at least one HPV infection. The HPV serotypes that cause more prolonged infection tend to be those that more frequently result in the development of histological abnormalities.5, 6

Those who are immune compromised (due to medical conditions or treatment) are more likely to develop a persistent HPV infection and to subsequently progress to HPV-related disease.7, 8

Those with confirmed HIV infection are more at risk of HPV infection.9 HIV-infected individuals who are co-infected with HPV are less likely to become undetectable.10, 11 A direct relationship has been identified between low CD4 cell count and an increased risk of cervical cancer in HIV-infected women.12

Men who have sex with men (MSM), especially those that are HIV-positive, are at higher risk for HPV infection, anal cancer and high-grade anal intraepithelial neoplasia (HGAIN).13

9.2.2 Cervical cancerTop

HPV rapidly becomes undetectable in the first 6–12 months, with 80–90 percent undetectable by two years. Following this, there is a very small fraction of persistent infection that progresses to cervical intraepithelial neoplasia (CIN); these are non-invasive precancerous lesions, which are categorised as either low or high grade CIN. Invasive cervical cancer occurs when the lesions invade the cervical tissue, and is graded from stage I to IV, depending on how far the cancer has spread beyond the cervix into surrounding tissue or organs.

Cervical cancer does not usually develop until decades after acquisition of infection with an oncogenic (cancer-causing) HPV serotype. Persistent HPV infection is detected in almost all women with cervical cancer.

HPV infection, while essential for the development of cervical cancer, is not, by itself, sufficient. Other factors have been described that may be associated with HPV persistence and high-grade lesions including smoking, early onset sexual activity, older age, contraceptive use, multiple sexual partners and genetic factors.14, 15

9.2.3 Other cancersTop

The clinical features of other HPV-associated cancers and their precancerous lesions in the anogenital region and oropharynx vary, and also depend on the anatomical site.16 The progression from HPV-associated precancer lesions to cancers in these sites is less well understood than the process in the cervix.

9.2.4 Genital wartsTop

HPV6 and 11 account for around 90 percent of all genital warts cases. The majority of warts cases are self-limited, although some may persist for several years. Persistence is more common in patients with impaired cell-mediated immunity.1

9.2.5 Respiratory papillomatosisTop

Perinatal transmission of HPV virus (usually HPV types 6 or 11) can cause laryngeal infection in infants, which in rare cases can result in recurrent respiratory papillomatosis (RRP) in children. RRP is characterised by multiple warty growths on the mucosal surface of the respiratory tract, which can significantly obstruct the airways.16