Human Papillomavirus Vaccines

2.1

Genital and Laryngeal Warts

GWs are the commonest viral sexually transmitted infection with a peak incidence between 15–25 years and an overall population incidence per annum of 0.16–0.2% in economically developed countries. Methodologically robust HPV detection and typing assays reveal that 96% or more of GWs are caused by HPV 6 or 11.

Recurrent respiratory papillomatosis is a rare disease with an incidence rate of 0.5/100,000 live births. HPVs 6 and 11 are the causal agents with HPV 11 predominating. Although the lesions are histologically benign, morbidity is significant since the frequent recurrence and often confluent spread of these lesions make treatment difficult and patients usually require multiple surgical interventions for excision of lesions.

2.2

Invasive Cancer

Globally, it is estimated, that more than 610,000 cancer cases per annum are attributable to HPV infection. The vast majority of these, 530,000 cases, are cervical cancer followed by anus, oropharynx, vulva, penis, and vagina ( Fig. 13.1 ). More than 86% of cervical cancers occur in economically undeveloped countries. This discrepancy in cervical cancer incidence between economically developed and undeveloped can be attributed very largely to cervical cancer screening programs in developed countries. Invasive cervical cancer is preceded by epithelial atypia: cervical intraepithelial neoplasia (CIN) in squamous cell carcinoma and adenocarcinoma in situ (AIS) in adenocarcinoma. CIN represents a spectrum of atypia in squamous epithelia ranging from mild (CIN1), moderate (CIN2) to severe or high grade (CIN3); CIN3 and AIS are usually accepted as the obligate precursor lesions of invasive cervical carcinoma. The objective of cervical cancer screening is to detect these high grade lesions and remove them by ablative or excisional procedures, thus interrupting progression to malignant disease in the screened population.

Intraepithelial atypia comparable to the cervical spectrum precede anal, vulval, vaginal, and penile cancers but the natural history of these precursor lesions and progression to malignant disease is not well-documented and understood as for the cervix. Screening is either not available or not feasible for noncervical HPV-associated cancers and the precursor lesions and the available data from economically developed countries show that the incidence of these cancers is rising in these locales. Thus the incidence of anal cancer has risen by 2–3% per annum over the past 3–4 decades irrespective of age in the United Kingdom, the Nordic countries, the USA, Australia, and Canada to name but a few. The incidence of oropharyngeal squamous cell carcinoma (OPSCC) has more than doubled over the past decade in some European countries, the USA, Canada, and Australia. These increases correlate strongly with the rise in the proportion of HPV positive OPSCC over the period from 1980 onward. The rise is greater, two- to threefold, in men than women and in contrast to HPV negative cancers, HPV positive OPSCC occur in younger age groups (<60 years), is unrelated to tobacco use but is associated with oral sex consistent with the evidence that sexual behaviors have changed among the recent birth cohorts in developed countries.

2.3