List of abbreviations used in this report
3 Burden of disease
3.6 Risk factors for cervical cancer
3.6.1 Burden of HPV in women
3.6.1.2 Prevalence of hrHPV in borderline and low-grade abnormalities
This section considers the prevalence of hrHPV in borderline and low-grade abnormalities. Given the propensity of hrHPV to cause invasive cervical cancer, infection with hrHPV genotypes can manifest as abnormal cytological changes in
70 cervical cells. These early cytological changes, referred to as borderline or low-grade abnormalities may regress spontaneously or persist and develop into high-grade abnormalities which in turn may progress to invasive cervical cancer. Therefore, prevalence of hrHPV would be expected to increase with increasing grade of cytological abnormality.
According to a 2010 report of the Catalan Institute of Oncology, global prevalence of HPV 16 and 18 genotypes in LSIL is estimated to be 24.3% (95% CI: 23.6 to
25.0).(134) European prevalence is estimated to be slightly lower (23.9%) with evidence of regional variation. Prevalence ranges from 32.6% in Eastern Europe to 20.8% in Western Europe. Northern Europe (which includes Ireland) has an
estimated prevalence of 30.3% (95% CI: 27.6 to 33.1).(134) HPV 16 and 18 genotypes are estimated to contribute to 16 to 32% of LSIL.(134)
A meta-analysis published in 2009 by Arbyn et al. compared prevalence of hrHPV in ASCUS and LSIL.(143) On average, 43% (95% CI: 40 to 46) of ASCUS (range 23% to 74%) and 76% (95% CI: 71 to 81) of LSIL (range 55% to 89%) were hrHPV
positive.(143)
The UK-based ARTISTIC trial, reported rising rates of HPV positivity with increasing grade of cytological abnormality.(137) The ARTISTIC study used the BSCC classification system which classifies ASCUS as a borderline nuclear abnormality and LSIL as mild dyskaryosis (see Chapter 2, Table 2.2). The prevalence of hrHPV in borderline nuclear abnormalities and mild dyskaryosis were 31% and 70%, respectively.(137)
A population-based study of women aged 20 to 64 years who attended cervical screening in Northern Ireland , reported that 7.3% of samples had low-grade abnormalities.(138) Of these, 68.8% were hrHPV positive. HPV 16 was the most prevalent HPV genotype detected in low-grade abnormalities.(138)
A study conducted in the Republic of Ireland of 996 women aged 16 to 72 years who were opportunistically screened by their general practitioner, reported that 11.1% of samples had a cytological abnormality.(139) Just over 87% (96/110) of samples with a cytological abnormality had a positive result for HPV. HPV 16 was the most
prevalent genotype in samples with mild, moderate or severe dyskaryosis (BSCC terminology, see Chapter 2, Table 2.2).
A study which included data from opportunistic and organised screening in Northern Ireland and the Republic of Ireland included women between the ages of 17 and 89 years.(140) ASCUS was detected in 5.8% of samples and LSIL was detected in 3.9%
of samples.(140) Prevalence of hrHPV in ASCUS samples was 56.8% (95% CI: 50.8%
to 62.7%).(140) It was 71.2% in women under the age of 30 years and 47.3% in
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71 women aged 30 years or older.(140) In LSIL samples, the prevalence of hrHPV was 83.2% (95% CI: 77.7% to 88.7%). It was 90.2% in women under the age of 30 years and 76.6% in women aged 30 years or older.(140)
In May 2015 HPV triage testing commenced in CervicalCheck laboratories.(111) Smear test samples reported as ASCUS or LSIL are reflex tested for the presence of hrHPV genotypes. Between 1 June 2015 and 31 July 2016, a total of 278,172 screening tests were carried out in non-colposcopy settings.(144) ASCUS and LSIL were reported in 3.4% (n=9,308) and 2.8% (n=7,813) of samples, respectively.(144) A small number of ASCUS and LSIL samples (n=(6+8)=14) had an indeterminate hrHPV test result or were not tested for hrHPV. The crude prevalence of hrHPV was 38.5% and 71.1% in ASCUS and LSIL samples, respectively. The crude prevalence of hrHPV in ASCUS and LSIL samples was highest in women under the age of 30 years. (Table 3.7).
72 Table 3.7 Prevalence of hrHPV in ASCUS and LSIL samples in
non-colposcopy settings, 1 June 2015 to 31 July 2016 ASCUS
Age Total tested
(n) hrHPV +ve (n) (%)
< 20 3 1 (33.3)
20 - 24 24 18 (75.0)
25 - 29 2,596 1,583 (61.0)
30 - 34 1,807 811 (44.9)
35 - 39 1,631 490 (30.0)
40 - 44 1,372 319 (23.3)
45 - 49 982 177 (18.0)
50 - 54 452 100 (22.1)
55 - 59 253 50 (19.8)
60 - 64 128 27 (21.1)
65 - 69 45 8 (17.8)
70 - 74 12 1 (8.3)
>= 75 3 0 (0.0)
Total 9,308 3,585 (38.5)
LSIL
Age Total tested
(n) hrHPV +ve (n) (%)
< 20 0 0 (0.0)
20 - 24 35 28 (80.0)
25 - 29 3,367 2,733 (81.2)
30 - 34 1,687 1,184 (70.2)
35 - 39 1,120 710 (63.4)
40 - 44 773 466 (60.3)
45 - 49 485 249 (51.3)
50 - 54 193 99 (51.3)
55 - 59 106 59 (55.7)
60 - 64 31 17 (54.8)
65 - 69 13 4 (30.8)
70 - 74 2 2 (100.0)
>= 75 1 1 (100.0)
Total 7,813 5,552 (71.1)
Data provided by CervicalCheck
The number positive are the number with ASCUS or LSIL who tested positive for hrHPV. The % calculation provided in brackets after this is the prevalence of hrHPV within that age band. For example, 1,583, or 61% of the 2,596 25 to 29 year olds with ASCUS were hrHPV positive.
Prevalence of hrHPV shown in Table 3.8 were obtained from screening tests taken in colposcopy settings and are not segregated by test purpose. They include women tested after treatment for high-grade abnormalities and those who are untreated
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73 and typically present with persistent low-grade abnormalities. Smaller numbers of ASCUS and LSIL results were obtained from these tests. Overall crude prevalence of hrHPV in 1,348 ASCUS samples was 44.4% while it was 72.0% in 2,506 LSIL
samples. This was similar to the overall crude prevalence of hrHPV in the LSIL samples taken in non-colposcopy settings (71.1%).
74 Table 3.8 Prevalence of hrHPV in ASCUS and LSIL samples in colposcopy,
1 June 2015 to 31 July 2016 ASCUS
Age Total tested
(n) hrHPV +ve (n) (%)
< 20 2 0 (0.0)
20 - 24 28 9 (32.1)
25 - 29 325 102 (31.4)
30 - 34 306 137 (44.8)
35 - 39 240 123 (51.3)
40 - 44 184 94 (51.1)
45 - 49 111 61 (55.0)
50 - 54 71 36 (50.7)
55 - 59 49 24 (49.0)
60 - 64 21 9 (42.9)
65 - 69 8 1 (12.5)
70 - 74 3 2 (66.7)
>= 75 0 0 (0.0)
Total 1,348 598 (44.4)
LSIL
Age Total tested
(n) hrHPV +ve (n) (%)
< 20 2 2 (0.0)
20 - 24 52 43 (82.7)
25 - 29 609 481 (79.0)
30 - 34 613 449 (73.2)
35 - 39 383 254 (66.3)
40 - 44 294 202 (68.7)
45 - 49 223 149 (66.8)
50 - 54 158 103 (65.2)
55 - 59 105 75 (71.4)
60 - 64 44 31 (70.5)
65 - 69 19 13 (68.4)
70 - 74 4 2 (50.0)
>= 75 0 0 (0.0)
Total 2,506 1,804 (72.0)
Data provided by CervicalCheck
Preliminary data from an observational study being undertaken by CERVIVA in collaboration with CervicalCheck, to evaluate and compare different strategies for the triage of women with HPV/mRNA positive primary screening tests, have been made available to inform this HTA.(142) Cytology results were available for the first
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75 1,973 study participants enrolled in the study. A total of 1.5% and 3.6% of samples were reported to have ASCUS and LSIL, respectively. The prevalence of hrHPV in samples with ASCUS and LSIL was 56.7% and 70.4%, respectively. It was higher in women under the age of 30 years than it was in older women. Of note, as this study is nested within CervicalCheck, these data are also captured within the triage data reported above. Partial genotyping from 1,000 samples indicate that 12.5% (95%
CI: 1.6 to 38.3) of ASCUS samples (2/16) were positive for HPV 16, none (95% CI: 0 to 20.6) were positive for HPV 18 (0/16) and 44% (95% CI: 19.8 to 70.1) were positive for other hrHPV genotypes (7/16). Partial genotyping of LSIL samples that were positive for HPV DNA indicated that 20% (95% CI: 8.4 to 36.9) were positive for HPV 16 (7/35), 2.9% (95% CI: 0.1 to 14.9) were positive for HPV 18 (1/35), and 43% (95% CI: 26.3 to 60.6) were positive for other hrHPV genotypes (15/35). At this point, the number in the cohort with ASCUS and LSIL is small (16 and 35, respectively) and the estimates are subject to substantial imprecision.
A prospective study conducted by CERVIVA in collaboration with CervicalCheck, between October 2008 and July 2011 investigated hrHPV DNA testing and
p16INK4a/Ki-67 staining in the detection of CIN 2+ in women referred to colposcopy with repeat ASCUS and LSIL.(145) The study comprised 471 women who attended their first colposcopy visit at a Dublin centre. HPV DNA was positive in 50.5% of ASCUS referrals and 71.7% of LSIL referrals.(145)
A population based study conducted in Northern Ireland which was published in 2015, aimed to identify the HPV genotypes predominating in histological
precancerous abnormalities and invasive cervical cancers in women attending
screening services.(146) Of the 1,830 eligible samples, 68.0% tested positive for HPV, 95.2% of which tested positive for hrHPV. The prevalence of hrHPV in CIN 1
samples was 48.1%.
In summary, triage data from CervicalCheck, indicate a crude prevalence of hrHPV of 38.5% with ASCUS.(144) This prevalence is lower than that observed in two published Irish studies, however these are not directly comparable due to differences in the study populations. Preliminary data from CERVIVA in collaboration with
CervicalCheck, indicate a crude prevalence of hrHPV of 56.7%.However, ASCUS was reported in only 30 smear tests. The Irish data indicate a higher prevalence that the UK-based ARTISTIC trial which reported a prevalence of hrHPV of 31% with
borderline nuclear abnormalities (see Chapter 2, Table 2.2). The UK data were based on women aged 20 to 64 years. The difference in prevalence of HPV persisted when Irish data were restricted to women aged 20 to 64 years. The data are not directly comparable due to differences in HPV detection methods and classification systems.
76 Published Irish hrHPV prevalence data for LSIL ranges from 71.1% to 83.2%. Data from CervicalCheck, comprising triage date for women with LSIL identified from primary LBC-based screening indicate a crude prevalence of hrHPV of 71.1%. This is consistent also with the preliminary data from the CERVIVA study which is nested in CervicalCheck and which reports a crude prevalence of 70.4% (based on small numbers). These data are also broadly consistent with prevalence of hrHPV reported by the UK-based ARTISTIC trial(137) and the meta-analysis published by Arbyn et al.
in 2009.(143)
3.6.1.3 Prevalence of hrHPV with high-grade abnormalities and