We have used anonymous, residual, cervical cytology (LBC) samples and biopsies of cervical cancers and high-grade lesions, collected from eight sites, to describe type-specific HPV prevalence in women in England, across the full spectrum of cervical pathology, from normal to cancer.
Assuming the relative frequency of SCC and ADC in our study are representative of all cervical cancers, our results suggest that at least 73% of cervical cancers in England are potentially preventable by type-specific protection from HPV 16/18 immunisation (i.e., are infected with HPV 16 and/or 18 only), rising to around 77% if co-infection with other HR types is never the causative HPV infection. Similarly, at least 56% and up to 65% of CIN3/CGIN are potentially preventable by HPV 16/18 immunisation. The difference between the percentage of cases with HPV 16 and/or 18 only (minimum attributable fraction), and the percentage with HPV 16 and/or 18 and another HR HPV (probable attributable fraction), indicates the potential for unmasking of disease caused by other HR HPV types if HPV 16 and 18 infections are prevented. By the same reckoning, between 32 and 49% of the moderate and 40 and 64% of the severe dyskaryotic cervical abnormalities identified by cervical screening may be preventable by HPV 16/18 immunisation.
HPV 31 and 45 were each associated (without HPV 16 and/or 18, but with or without other HR types) with an additional 3% of SCC and 2% of ADC. As there is some evidence of cross-protection from current HPV 16/18 vaccines against infection and disease due to these types and HPV 33, 52 and 58, which are closely related to HPV 16 or HPV 18 (Brown et al, 2009
; Paavonen et al, 2009
), the benefits of immunisation may include reduction in these cancers also. If cross-protection against HPV 31, 33, 45, 52 and 58 ranges from 25 to 29%, as suggested currently by clinical trials (Brown et al, 2009
; Paavonen et al, 2009
), our findings suggest that HPV 16/18 immunisation may prevent an additional 3–4% of cervical cancers in England.
Other studies of HPV type distribution in cervical cancers in the United Kingdom have reported similarly high fractions of cases probably attributable to HPV 16 and/or 18. Cuzick et al (2000)
analysed cervical scrapes from 116 women with cervical cancer and found HPV 16 and/or 18 in 78% of SCC and 71% of ADC (including adenocarcinoma and adeno-squamous carcinoma). In Scotland, Tawfik El-Mansi et al (2006)
found HPV 16 and/or 18 in 61% of ADC diagnosed between 1991 and 2001, and Cuschieri et al (2010)
detected HPV 16 and/or 18 in 72% of 370 invasive cervical cancers diagnosed up to 2004. In Wales, Powell et al (2009)
found HPV 16 and/or 18 in 80% of SCC (N
=222) and 91% of ADC (N
=47) diagnosed between 2000 and 2006. Three other studies have looked at fewer than 50 cases each (Crook et al, 1992
; Arends et al., 1995
; Giannoudis et al, 1999
). The differences between these United Kingdom-based studies may reflect differences in HPV typing methods, and/or chance, and do not suggest significant variations between countries in the contribution of HPV 16 and/or 18 to cervical cancer incidence that are likely to have important effect on the impact of immunisation.
Our results are consistent with previous suggestions that a higher proportion of disease in Europe will be preventable by current HPV 16/18 vaccines than some other areas of the world (Muñoz et al, 2004
; Li et al, 2010
), mostly because of higher HPV 16 prevalence. Furthermore, the most common non-vaccine types identified in our study (HPV 33, 45, 52 and 31) were among the most common types found in international studies, albeit not in exactly the same ranking (Clifford et al, 2003
; Muñoz et al, 2004
; Li et al, 2010
Several studies have reported data on HPV prevalence in women attending for cervical screening in the United Kingdom (Cuschieri et al, 2004
; Peto et al, 2004
; Kitchener et al, 2006
; Hibbitts et al, 2008
). In England, HR HPV prevalence of 16% (samples collected between 2001 and 2003) (Kitchener et al, 2006
) and 7% (samples collected between 1988 and 1993) (Peto et al, 2004
) have previously been reported from studies conducted in Manchester. In south Wales (2008), HR HPV prevalence of 11% has been reported (Hibbitts et al, 2008
), while in Scotland (2004), HR HPV prevalence of 16% has been reported (Cuschieri et al, 2004
). In our study, the weighted (by age and cytology grade) prevalence of HR HPV was 16% (95% CI 11–22). These studies from across the United Kingdom also report fairly consistent results with respect to the prevalence of HPV 16 and/or 18. Differences in the age range, HPV typing methods, sample types and chance variation may account for some differences between studies. Differences may also reflect increases in prevalence over time, as the lowest HR HPV prevalence (7%) was found in the earliest study (Peto et al, 2004
), over a period when there has been an increasing frequency of clinically apparent HPV 6 and 11 infection as cases of genital warts (Health Protection Agency, 2008
Strengths of our study include collection of both LBC samples and biopsy samples from a number of sites geographically spread across England, and testing for the same HPV types. The stratified sampling of LBCs from each centre enabled the description of type-specific infection in more severe cytology abnormalities and from older women.
This was a cross-sectional study of a disease state that spans a long time course of progression from infection to cancer: when comparing the type distribution in cancers and in lower grade disease we cannot therefore rule out any affect from the profile of HPV types in the population changing over time. Unfortunately, data on ethnicity, deprivation and sexual behaviour were not available with our samples and therefore the association between these factors and HPV prevalence could not be analysed.
Our estimates of prevalence are based on cervical screening. As repeat screens from individuals were not excluded and may be expected to have a higher HPV prevalence, our estimates may overestimate population prevalence among screened women (as do those from other similar studies of cervical screens). Our prevalence estimates do not provide data on the 20% of the population who do not regularly attend for screening (The NHS Information Centre, 2009
), and who would have more to gain from immunisation.
This is the first study to describe comprehensively type-specific HPV prevalence across England, including samples from women with normal cytology and all stages of cervical disease in order to be able to estimate the proportion of disease potentially preventable, nationally, by immunisation. These data will be used in models to assess the likely benefit from HPV immunisation (Jit et al, 2008
; Choi et al, 2009
), and as baseline data against which to evaluate changes in type-specific HPV prevalence and type distribution after the introduction of the HPV immunisation programme. The findings support optimism regarding high impact of the National HPV (16/18) Immunisation Programme on cervical disease in England.