Human Papillomavirus Genotype Distributions: Implications for Vaccination and Cancer Screening in the United States

Abstract

BackgroundLimited data are available describing human papillomavirus (HPV) genotype distributions in cervical cancer in the United States. Such studies are needed to predict how HPV vaccination and HPV-based screening will influence cervical cancer prevention.MethodsWe used the New Mexico Surveillance, Epidemiology, and End Results Registry to ascertain cases of in situ (n = 1213) and invasive (n = 808) cervical cancer diagnosed during 1985–1999 and 1980–1999, respectively, in the state of New Mexico. HPV genotyping was performed using two polymerase chain reaction–based methods on paraffin-embedded tissues from in situ and invasive cancers and on cervical Papanicolaou test specimen from control subjects (ie, women aged 18–40 years attending clinics for routine cervical screening [n = 4007]). Relative risks for cervical cancer were estimated, and factors associated with age at cancer diagnosis and the prevalence of HPV genotypes in cancers were examined.ResultsThe most common HPV genotypes detected in invasive cancers were HPV type 16 (HPV16, 53.2%), HPV18 (13.1%), and HPV45 (6.1%) and those in in situ cancers were HPV16 (56.3%), HPV31 (12.6%), and HPV33 (8.0%). Invasive cancer case subjects who were positive for HPV16 or 18 were diagnosed at younger ages than those who were positive for other carcinogenic HPV genotypes (mean age at diagnosis: 48.1 [95% confidence interval {CI} = 46.6 to 49.6 years], 45.9 [95% CI = 42.9 to 49.0 years], and 52.3 years [95% CI = 50.0 to 54.6 years], respectively). The proportion of HPV16-positive in situ and invasive cancers, but not of HPV18-positive cancers, declined with more recent calendar year of diagnosis, whereas the proportion positive for carcinogenic HPV genotypes other than HPV18 increased.ConclusionsHPV16 and 18 caused the majority of invasive cervical cancer in this population sample of US women, but the proportion attributable to HPV16 declined over the last 20 years. The age at diagnosis of HPV16- and HPV18-related cancers was 5 years earlier than that of cancers caused by carcinogenic HPV genotypes other than HPV16 and 18, suggesting that the age at initiation of cervical screening could be delayed in HPV-vaccinated populations.

HPV Type Attribution in High-Grade Cervical Lesions: Assessing the Potential Benefits of Vaccines in a Population-Based Evaluation in the United States

“…As expected, among the unvaccinated women, we found that HPV16/18 attribution was highest in the youngest age group and significantly decreased by age. The relatively lower proportions of HPV16/18-attributable lesions in the older group are congruent with epidemiologic evidence of stronger carcinogenic potential and faster progression of HPV16/ 18-associated lesions compared with lesions due to other highrisk types, and similar results have been shown in other studies (16,17,22,23).…”

“…Although currently available HPV vaccines have shown some cross-protective efficacy against nonvaccine oncogenic types (13-15), a substantial proportion of high-grade cervical lesions are caused by types against which current vaccines have not shown any degree of efficacy (11,16,17). Vaccines that target a wider array of oncogenic HPV types such as a candidate vaccine against 6/11/16/18 and 5 additional oncogenic types (31/33/45/52/58) could provide additional protection against precancerous lesions that require treatment.…”

Importance of HPV Genotyping for the Screening, Therapy and Management of Cervical Neoplasias

“…Moreover, the women in whom one of these 3 HPV genotypes was detected were approximately 4 years younger when the cancers were detected compared to women in whom other HPV genotypes were determined in their cancer cells. An American study of 1213 women with carcinoma in situ (CIN 3) and 808 women with invasive cervical cancer detected HPV DNA in 97.1 % of CIN 3 lesions and in 91.0 % of invasive carcinomas [8]. Once again, HPV 16 was the most common genotype with an incidence of 56.3 and 53.2 %, respectively.…”

EUROGIN 2008 roadmap on cervical cancer prevention

“…HPV18 and 45, however, are under represented in CIN3 compared to cervical cancer. 70 CIN2, on the other hand is a clinically significant lesion, but represents a combination of true precursors and a low-grade lesions, with a mixture of HPV types and poor diagnostic reproducibility. 71 The composite trial outcome of CIN21 is a compromise between diagnostic reproducibility, positive predictive value, clinical relevance and high incidence, which provides the necessary efficacy data with trials of a reasonable size.…”

“…Great benefit from linkage of HPV typing data will be realised in settings where population-based screening and vaccination registries have been established prior to, or early on in HPV vaccine implementation. 76 The use of historical rates from the untreated group of previous clinical trials has the advantage of randomisation and probably the availability of HPV typing data and carefully documented risk factor and clinical outcome data. However, there are a limited number of such trials and they have most often been conducted in ill-defined populations (e.g., volunteers), presenting challenges to reduce potential selection bias.…”