Risk of newly detected infections and cervical abnormalities in adult women seropositive or seronegative for naturally acquired HPV‐16/18 antibodies

Abstract

Background Infections with human papillomavirus (HPV) types 16 and 18 account for ~70% of invasive cervical cancers but the degree of protection from naturally acquired anti‐HPV antibodies is uncertain. We examined the risk of HPV infections as defined by HPV DNA detection and cervical abnormalities among women >25 years in the Human Papilloma VIrus Vaccine Immunogenicity ANd Efficacy trial's (VIVIANE, NCT00294047) control arm. Methods Serum anti‐HPV‐16/18 antibodies were determined at baseline and every 12 months in baseline DNA‐negative women (N = 2687 for HPV‐16 and 2705 for HPV‐18) by enzyme‐linked immunosorbent assay (ELISA) from blood samples. HPV infections were identified by polymerase chain reaction (PCR) every 6‐months, and cervical abnormalities were confirmed by cytology every 12 months. Data were collected over a 7‐year period. The association between the risk of type‐specific infection and cervical abnormalities and serostatus was assessed using Cox proportional hazard models. Results Risk of newly detected HPV‐16‐associated 6‐month persistent infections (PI) (hazard ratio [HR] = 0.56 [95%CI:0.32; 0.99]) and atypical squamous cells of undetermined significance (ASC‐US+) (HR = 0.28 [0.12; 0.67]) were significantly lower in baseline seropositive vs baseline seronegative women. HPV‐16‐associated incident infections (HR = 0.81 [0.56; 1.16]) and 12‐month PI (HR = 0.53 [0.24; 1.16]) showed the same trend. A similar trend of lower risk was observed in HPV‐18‐seropositive vs ‐seronegative women (HR = 0.95 [0.59; 1.51] for IIs, HR = 0.43 [0.16; 1.13] for 6‐month PIs, HR = 0.31 [0.07; 1.36] for 12‐month PIs, and HR = 0.61 [0.23; 1.61] for ASC‐US+). Conclusions Naturally acquired anti‐HPV‐16 antibodies were associated with a decreased risk of subsequent infection and cervical abnormalities in women >25 years. This possible protection was lower than that previously reported in 15‐ to 25‐year‐old women.

HPV vaccination among seropositive, DNA negative cohorts: a systematic review & meta-analysis

“…‘cryptic, persistent, and reversible infection of cells’ [ 56 ], rather than true eradication [ 54 57 58 ]. Data regarding immunity following such ‘cleared’ natural infections is inconsistent [ 50 59 60 61 62 ], but it is likely that natural infection, perhaps particularly among younger women [ 63 ], offers a modest degree of protection against type-specific, clinically apparent or DNA-detectable, reinfection [ 64 ].…”

Human papillomavirus seroprevalence and seroconversion following baseline detection of nine human papillomavirus types in young women

“…Young women (15–25 years) enrolled in the control arms of the Costa Rica Vaccine Trial and the PATRICIA Trial who had naturally acquired HPV 16 or HPV 18 seropositivity at baseline had partial protection against subsequent HPV 16 or HPV 18 incident HPV DNA detection, and ASC-US or worse Pap results, compared with women who were seronegative [ 29 ]. Adult women in the control group of the VIVIANE Trial who were seropositive for HPV 16 at baseline also had evidence of partial protection; however, little-to-no protection was observed among those who were seropositive for HPV 18 at baseline [ 30 ]. In an analysis of young women (16–26 years) from three 4vHPV vaccine clinical trials who were HPV DNA‒negative but seropositive to a specific HPV type (6/11/16/18) at baseline, subsequent cervical or external genital disease related to one of the 4vHPV types during follow-up (approximately 40 months) was observed in some women in the placebo arm, whereas no cases of subsequent disease were observed in vaccinated women [ 31 ].…”

Seroprevalence of mucosal and cutaneous human papillomavirus (HPV) types among children and adolescents in the general population in Germany

“…It has been discussed whether the development of HPV antibodies (and more generally an HPV infection) in early childhood protects from HPV infection or HPV associated diseases in later life [ 62 , 77 , 78 ]. Naturally acquired HPV antibodies provide protection against subsequent cervical HPV infections [ 79 ].…”

“…Naturally acquired HPV antibodies provide protection against subsequent cervical HPV infections [ 79 ]. However, the effect of naturally acquired infections on immunity seems to be modest and type-specific, as the effect was only observed for HPV-16 infections [ 78 , 79 ]. Rodriguez et al [ 80 ] showed that type-specific HPV infections may reappear and may lead to precancerous lesions in previously exposed individuals, even though the risk was low.…”