Naturally Acquired Immunity Against Human Papillomavirus (HPV): Why It Matters in the HPV Vaccine Era

(See the major article by Castellsagué et al on pages 517–34.) Scientists do not know precisely which elements of the immune system are important in preventing or resolving human papillomavirus (HPV) infections in unvaccinated women. HPV has a battery of immune-evasion mechanisms that include hiding within the host mucosal cells, low-level production of late (L) proteins, and inhibition of innate immunity and cell-mediated response by early proteins [1]. HPV vaccine trials show that sufficiently high levels of neutralizing antibodies against viral capsid strongly protect women who are negative for vaccine types at baseline against homologous (same-type) HPV infection. The measurement of HPV antibodies is also important for identifying unvaccinated women who have mounted an antibody response following previous exposure to HPV infection and may, therefore, be naturally protected. However, only approximately half of women seroconvert within 18 months after HPV infection [2]. The interpretation of HPV serology is additionally complicated by substantial differences across assays used in different studies (eg, detection ranges, targeted HPV types, and epitopes) [3–5]. Despite these limitations, seroprevalence studies have been essential in understanding HPV exposure [6] and infection trends [7], and have more recently started providing prospective estimates of naturally acquired immunity after HPV infection [4].