Accepted Manuscript Towards cervical cancer eradication: joint force of HPV vaccination and HPV-based cervical cancer screening Mario Poljak, MD, PhD, Prof. PII:
S1198-743X(15)00589-3
DOI:
10.1016/j.cmi.2015.05.041
Reference:
CMI 300
To appear in:
Clinical Microbiology and Infection
Received Date: 22 May 2015 Accepted Date: 29 May 2015
Please cite this article as: Poljak M, Towards cervical cancer eradication: joint force of HPV vaccination and HPV-based cervical cancer screening, Clinical Microbiology and Infection (2015), doi: 10.1016/ j.cmi.2015.05.041. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT
1
EDITORIAL
2
Towards cervical cancer eradication: joint force of HPV vaccination and HPV-
3
based cervical cancer screening
RI PT
4 Mario Poljak
5 6
Institute of Microbiology and Immunology, Faculty of Medicine, University of Ljubljana, Slovenia
8
2
M AN U
9
SC
7
10 11
This Editorial is part of the themed section on HPV, September 2015 issue of CMI.
12
Guest Editor: Mario Poljak
13
16 17
EP
15
TE D
14
Corresponding author: Prof. Mario Poljak, MD, PhD, Institute of Microbiology and
19
Immunology, Faculty of Medicine, University of Ljubljana, Zaloška 4, 1105 Ljubljana, Slovenia.
20
Tel.: +386 1 543 7453. Fax: +386 1 543 7418. E-mail: [email protected].
21
AC C
18
1
ACCEPTED MANUSCRIPT
Human papillomaviruses (HPV) are etiologically linked to the development of various benign
23
and malignant lesions of the skin and mucosa [1–4]. The current theme issue addresses four
24
burning topics connected with HPV. In the first article, the most frequently used molecular
25
methods for identification and characterization of novel papillomaviruses were reviewed [5].
26
These methods have allowed an explosive increase in the identification of novel HPV types in
27
last few years. Currently, 200 different HPV types, ranging from HPV-1 to HPV-204 (HPV-46,
28
HPV-55, HPV-64 and HPV-79 are now classified as subtypes), had been officially recognized
29
[5].
SC
RI PT
22
Two revolutionary technical advances have recently opened new prospects for the
31
prevention of cervical cancer: molecular HPV testing and prophylactic HPV vaccination [6,7],
32
reviewed in the second and third articles of this issue [8,9]. HPV testing is invaluable part of
33
guidelines for cervical carcinoma screening, triage and follow-up after treatment [10-11]. HPV-
34
based screening is more effective and efficient for the prevention of invasive cervical cancer
35
than cytology-based screening [11-13], thus several countries are now in the process of
36
switching to HPV-based screening. Given the multitude of available HPV tests (175+
37
commercial HPV assays and 100+ variants) [14,15], HPV tests that ensure high-quality cervical
38
cancer screening have to be urgently identified. In the systematic review, Arbyn at al [8]
39
identified seven commercially available HPV DNA assays which can be recommended at
40
present as reliable tools in HPV-based screening using clinician-collected cervical samples,
41
based on criteria defined by an international expert team [16]. One E6/E7 mRNA-based assay
42
also fully matches the criteria, although further longitudinal follow up data are awaited. Four
43
HPV DNA assays only partially fulfilled the guideline requirements [16].
AC C
EP
TE D
M AN U
30
44
Prophylactic HPV vaccination is the second revolutionary advance for the prevention of
45
cervical cancer. In the third article of this issue [9], Pils and Joura provide a review of the
46
milestones in the development of prophylactic HPV vaccines, starting from an investigational
47
proof-of-concept monovalent HPV-16 vaccine, through two current HPV vaccines: quadrivalent 2
ACCEPTED MANUSCRIPT
and bivalent, to the recently licensed ninevalent HPV vaccine [17]. High efficacy in preventing
49
high-grade precursors of cervical, vulvar, vaginal and anal cancer related to the vaccine HPV
50
types (and genital warts in the case of quadrivalent and ninevalent vaccines) led recently to a
51
paradigm shift from a female-only cervical cancer vaccine to a vaccine for the prevention of
52
several HPV-related diseases and cancers in both genders. Current evidence suggests that
53
vaccination prior to the start of sexual activity is most effective and that gender-neutral HPV
54
vaccination is the most logical way forward. Thus, Garland et al. [18] provide and discuss ideas
55
of how best to measure the effectiveness of male HPV vaccine programs. With the introduction
56
of gender-neutral HPV vaccination, post-vaccine monitoring will be critical for evaluating the
57
incremental impact of male vaccination. In contrast to established cervical cancer screening
58
programs, which we are also using for monitoring the real life effectiveness of HPV vaccines,
59
population-wide screening for HPV infection or HPV-related disease in males is not feasible and
60
could not be recommended. Real-time monitoring of HPV vaccine effectiveness in males will
61
thus require dedicated surveillance strategies. Garland et al. propose that monitoring the
62
prevalence of circulating anogenital HPV types using a sentinel surveillance model could offer a
63
good surrogate marker of early vaccine effectiveness in males [18]. However, such an approach
64
requires careful consideration of the most appropriate anatomical sites from which to collect
65
specimens, the best sampling methods and the most sensitive HPV assays to use [18].
EP
TE D
M AN U
SC
RI PT
48
Combined approach of universal and gender-neutral HPV vaccination, with screening
67
when appropriate, is the most compelling strategy significantly to reduce the burden of HPV-
68
related diseases and cancers in both genders. In the case of cervical cancer, HPV vaccination
69
and screening are not mutually exclusive, but act synergistically by intervening at different
70
points in the natural history of cervical cancer, and currently imply actions in women of different
71
ages. Adequately combined, two prevention options have the potential dramatically to reduce
72
cervical cancer incidence and mortality; no other neoplastic disease can in fact currently rival
73
the magnitude of this potential [19]. However, at present, these two powerful prevention
AC C
66
3
ACCEPTED MANUSCRIPT
strategies remain apparently unconnected and no country has yet adopted different screening
75
policies for vaccinated and unvaccinated women. The time is thus now right to begin to evaluate
76
strategies that combine HPV vaccination and cervical cancer screening in the best possible
77
way. HPV-based screening is probably the only rational way forward for screening primary
78
vaccinated cohorts, but the questions of when to start and how frequently to screen remain
79
open [10]. Prudent and synergistic use of HPV vaccination and HPV-based screening will likely
80
be the hallmark of success in the future, but uncoordinated adoption of these technologies in
81
opportunistic and non-universal conditions will only heighten the inequality that has
82
characterized cervical cancer prevention for so long [19].
84
M AN U
83
85
Transparency declaration
86
The author declares no conflict of interest.
TE D
87
SC
RI PT
74
Acknowledgments
89
This work was partially supported by the European Union’s Seventh Framework Programme for
90
research, technological development and demonstration under the CoheaHr project (grant
91
agreement No. HEALTH-F3-2013-603019).
93
AC C
92
EP
88
4
ACCEPTED MANUSCRIPT
94
References
95 1. Bernard HU, Burk RD, Chen Z, van Doorslaer K, zur Hausen H, de Villiers EM. Classification
97
of papillomaviruses (PVs) based on 189 PV types and proposal of taxonomic amendments.
98
Virology 2010;401:70–9.
RI PT
96
99
2. Rector A, Van Ranst M. Animal papillomaviruses. Virology 2013;445:213–23.
SC
100 101
3. de Villiers EM. Cross-roads in the classification of papillomaviruses. Virology 2013;445:2–10.
M AN U
102 103 104
4. Bzhalava D, Eklund C, Dillner J. International standardization and classification of human
105
papillomavirus types. Virology 2015;476:341–4.
106
5. Kocjan BJ, Bzhalava D, Forslund O, Dillner J, Poljak M. Molecular methods for identification
108
and characterization of novel papillomaviruses. Clin Microbiol Infect 2015;21 (this issue).
TE D
107
109
6. Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. Estimates of worldwide burden
111
of cancer in 2008: GLOBOCAN 2008. Int J Cancer 2010;127:2893–917.
EP
110
AC C
112 113
7. Walboomers JMM, Jacobs MV, Manos MM, Bosch X, Kummer A, Shah KV, et al. Human
114
papillomavirus is a necessary cause of invasive cervical cancer worldwide. J Pathol
115
1999;189:12–19.
116 117
8. Arbyn M, Snijders PJF, Meijer CJLM, Berkhof H, Cuschieri K, Kocjan BJ, Poljak M, Which
118
high-risk HPV assays fulfil criteria for use in primary cervical cancer screening? Clin Microbiol
119
Infect 2015;21 (this issue). 5
ACCEPTED MANUSCRIPT
120 121
9. Pils S, Joura EA. From the monovalent to the ninevalent HPV vaccine. Clin Microbiol Infect
122
2015;21 (this issue).
RI PT
123 124
10. Castle PE, Schmeler KM. HPV vaccination: for women of all ages? Lancet 2014;384:2178-
125
80.
SC
126
11. Arbyn M, Ronco G, Anttila A, Meijer CJLM, Poljak M, Ogilvie G, et al. Evidence regarding
128
HPV testing in secondary prevention of cervical cancer. Vaccine 2012;30 Suppl 5: F88-F99.
M AN U
127
129 130
12. Sankaranarayanan R, Nene BM, Shastri SS, Jayant K, Muwonge R, Budukh AM, et al. HPV
131
screening for cervical cancer in Rural India. N Engl J Med 2009;360:1385-94.
132
13. Ronco G, Dillner J, Elfstrom KM, Tunesi S, Snijders PJ, Arbyn M, et al. Efficacy of HPV-
134
based screening for prevention of invasive cervical cancer: follow-up off four European
135
randomised controlled trials. Lancet 2014;383: 524-32.
EP
136
TE D
133
14. Poljak M, Kocjan BJ. Commercially available assays for multiplex detection of alpha human
138
papillomaviruses. Expert Rev Anti Infect Ther 2010;8:1139-62.
139
AC C
137
140
15. Poljak M, Cuzick J, Kocjan BJ, Iftner T, Dillner J, Arbyn M. Nucleic acid tests for the
141
detection of human papillomaviruses. Vaccine 2012;30 (Suppl 5):F100-F106.
142 143
16. Meijer CJLM, Castle PE, Hesselink AT, Franco EL, Ronco G, Arbyn M, Bosch FX, Cuzick J,
144
Dillner J, Heideman DA, Snijders PJ. Guidelines for human papillomavirus DNA test
6
ACCEPTED MANUSCRIPT
145
requirements for primary cervical cancer screening in women 30 years and older. Int J Cancer
146
2009;124:516-20.
147 17. Joura EA, Giuliano AR, Iversen OE, Mehlsen MM, Moreira ED, Ngan Y et al. A 9-valent
149
HPV vaccine against infection and intraepithelial neoplasia in women. N Engl J Med
150
2015;372:711-23.
RI PT
148
SC
151
18. Garland SM, Molesworth EG, Machalek DA, Cornall A, Tabrizi SN. How to best measure the
153
effectiveness of male human papillomavirus vaccine programmes? Clin Microbiol Infect 2015;21
154
(this issue).
M AN U
152
155
19. Isidean SD, Coutlee F, Franco EL. Cobas 4800 HPV Test, a real-time polymerase chain
157
reaction assay for the detection of human papillomavirus in cervical specimens. Expert Rev Mol
158
Diagn 2014;14:5–16.
EP AC C
159
TE D
156
7
S1198-743X(15)00589-3
DOI:
10.1016/j.cmi.2015.05.041
Reference:
CMI 300
To appear in:
Clinical Microbiology and Infection
Received Date: 22 May 2015 Accepted Date: 29 May 2015
Please cite this article as: Poljak M, Towards cervical cancer eradication: joint force of HPV vaccination and HPV-based cervical cancer screening, Clinical Microbiology and Infection (2015), doi: 10.1016/ j.cmi.2015.05.041. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT
1
EDITORIAL
2
Towards cervical cancer eradication: joint force of HPV vaccination and HPV-
3
based cervical cancer screening
RI PT
4 Mario Poljak
5 6
Institute of Microbiology and Immunology, Faculty of Medicine, University of Ljubljana, Slovenia
8
2
M AN U
9
SC
7
10 11
This Editorial is part of the themed section on HPV, September 2015 issue of CMI.
12
Guest Editor: Mario Poljak
13
16 17
EP
15
TE D
14
Corresponding author: Prof. Mario Poljak, MD, PhD, Institute of Microbiology and
19
Immunology, Faculty of Medicine, University of Ljubljana, Zaloška 4, 1105 Ljubljana, Slovenia.
20
Tel.: +386 1 543 7453. Fax: +386 1 543 7418. E-mail: [email protected].
21
AC C
18
1
ACCEPTED MANUSCRIPT
Human papillomaviruses (HPV) are etiologically linked to the development of various benign
23
and malignant lesions of the skin and mucosa [1–4]. The current theme issue addresses four
24
burning topics connected with HPV. In the first article, the most frequently used molecular
25
methods for identification and characterization of novel papillomaviruses were reviewed [5].
26
These methods have allowed an explosive increase in the identification of novel HPV types in
27
last few years. Currently, 200 different HPV types, ranging from HPV-1 to HPV-204 (HPV-46,
28
HPV-55, HPV-64 and HPV-79 are now classified as subtypes), had been officially recognized
29
[5].
SC
RI PT
22
Two revolutionary technical advances have recently opened new prospects for the
31
prevention of cervical cancer: molecular HPV testing and prophylactic HPV vaccination [6,7],
32
reviewed in the second and third articles of this issue [8,9]. HPV testing is invaluable part of
33
guidelines for cervical carcinoma screening, triage and follow-up after treatment [10-11]. HPV-
34
based screening is more effective and efficient for the prevention of invasive cervical cancer
35
than cytology-based screening [11-13], thus several countries are now in the process of
36
switching to HPV-based screening. Given the multitude of available HPV tests (175+
37
commercial HPV assays and 100+ variants) [14,15], HPV tests that ensure high-quality cervical
38
cancer screening have to be urgently identified. In the systematic review, Arbyn at al [8]
39
identified seven commercially available HPV DNA assays which can be recommended at
40
present as reliable tools in HPV-based screening using clinician-collected cervical samples,
41
based on criteria defined by an international expert team [16]. One E6/E7 mRNA-based assay
42
also fully matches the criteria, although further longitudinal follow up data are awaited. Four
43
HPV DNA assays only partially fulfilled the guideline requirements [16].
AC C
EP
TE D
M AN U
30
44
Prophylactic HPV vaccination is the second revolutionary advance for the prevention of
45
cervical cancer. In the third article of this issue [9], Pils and Joura provide a review of the
46
milestones in the development of prophylactic HPV vaccines, starting from an investigational
47
proof-of-concept monovalent HPV-16 vaccine, through two current HPV vaccines: quadrivalent 2
ACCEPTED MANUSCRIPT
and bivalent, to the recently licensed ninevalent HPV vaccine [17]. High efficacy in preventing
49
high-grade precursors of cervical, vulvar, vaginal and anal cancer related to the vaccine HPV
50
types (and genital warts in the case of quadrivalent and ninevalent vaccines) led recently to a
51
paradigm shift from a female-only cervical cancer vaccine to a vaccine for the prevention of
52
several HPV-related diseases and cancers in both genders. Current evidence suggests that
53
vaccination prior to the start of sexual activity is most effective and that gender-neutral HPV
54
vaccination is the most logical way forward. Thus, Garland et al. [18] provide and discuss ideas
55
of how best to measure the effectiveness of male HPV vaccine programs. With the introduction
56
of gender-neutral HPV vaccination, post-vaccine monitoring will be critical for evaluating the
57
incremental impact of male vaccination. In contrast to established cervical cancer screening
58
programs, which we are also using for monitoring the real life effectiveness of HPV vaccines,
59
population-wide screening for HPV infection or HPV-related disease in males is not feasible and
60
could not be recommended. Real-time monitoring of HPV vaccine effectiveness in males will
61
thus require dedicated surveillance strategies. Garland et al. propose that monitoring the
62
prevalence of circulating anogenital HPV types using a sentinel surveillance model could offer a
63
good surrogate marker of early vaccine effectiveness in males [18]. However, such an approach
64
requires careful consideration of the most appropriate anatomical sites from which to collect
65
specimens, the best sampling methods and the most sensitive HPV assays to use [18].
EP
TE D
M AN U
SC
RI PT
48
Combined approach of universal and gender-neutral HPV vaccination, with screening
67
when appropriate, is the most compelling strategy significantly to reduce the burden of HPV-
68
related diseases and cancers in both genders. In the case of cervical cancer, HPV vaccination
69
and screening are not mutually exclusive, but act synergistically by intervening at different
70
points in the natural history of cervical cancer, and currently imply actions in women of different
71
ages. Adequately combined, two prevention options have the potential dramatically to reduce
72
cervical cancer incidence and mortality; no other neoplastic disease can in fact currently rival
73
the magnitude of this potential [19]. However, at present, these two powerful prevention
AC C
66
3
ACCEPTED MANUSCRIPT
strategies remain apparently unconnected and no country has yet adopted different screening
75
policies for vaccinated and unvaccinated women. The time is thus now right to begin to evaluate
76
strategies that combine HPV vaccination and cervical cancer screening in the best possible
77
way. HPV-based screening is probably the only rational way forward for screening primary
78
vaccinated cohorts, but the questions of when to start and how frequently to screen remain
79
open [10]. Prudent and synergistic use of HPV vaccination and HPV-based screening will likely
80
be the hallmark of success in the future, but uncoordinated adoption of these technologies in
81
opportunistic and non-universal conditions will only heighten the inequality that has
82
characterized cervical cancer prevention for so long [19].
84
M AN U
83
85
Transparency declaration
86
The author declares no conflict of interest.
TE D
87
SC
RI PT
74
Acknowledgments
89
This work was partially supported by the European Union’s Seventh Framework Programme for
90
research, technological development and demonstration under the CoheaHr project (grant
91
agreement No. HEALTH-F3-2013-603019).
93
AC C
92
EP
88
4
ACCEPTED MANUSCRIPT
94
References
95 1. Bernard HU, Burk RD, Chen Z, van Doorslaer K, zur Hausen H, de Villiers EM. Classification
97
of papillomaviruses (PVs) based on 189 PV types and proposal of taxonomic amendments.
98
Virology 2010;401:70–9.
RI PT
96
99
2. Rector A, Van Ranst M. Animal papillomaviruses. Virology 2013;445:213–23.
SC
100 101
3. de Villiers EM. Cross-roads in the classification of papillomaviruses. Virology 2013;445:2–10.
M AN U
102 103 104
4. Bzhalava D, Eklund C, Dillner J. International standardization and classification of human
105
papillomavirus types. Virology 2015;476:341–4.
106
5. Kocjan BJ, Bzhalava D, Forslund O, Dillner J, Poljak M. Molecular methods for identification
108
and characterization of novel papillomaviruses. Clin Microbiol Infect 2015;21 (this issue).
TE D
107
109
6. Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. Estimates of worldwide burden
111
of cancer in 2008: GLOBOCAN 2008. Int J Cancer 2010;127:2893–917.
EP
110
AC C
112 113
7. Walboomers JMM, Jacobs MV, Manos MM, Bosch X, Kummer A, Shah KV, et al. Human
114
papillomavirus is a necessary cause of invasive cervical cancer worldwide. J Pathol
115
1999;189:12–19.
116 117
8. Arbyn M, Snijders PJF, Meijer CJLM, Berkhof H, Cuschieri K, Kocjan BJ, Poljak M, Which
118
high-risk HPV assays fulfil criteria for use in primary cervical cancer screening? Clin Microbiol
119
Infect 2015;21 (this issue). 5
ACCEPTED MANUSCRIPT
120 121
9. Pils S, Joura EA. From the monovalent to the ninevalent HPV vaccine. Clin Microbiol Infect
122
2015;21 (this issue).
RI PT
123 124
10. Castle PE, Schmeler KM. HPV vaccination: for women of all ages? Lancet 2014;384:2178-
125
80.
SC
126
11. Arbyn M, Ronco G, Anttila A, Meijer CJLM, Poljak M, Ogilvie G, et al. Evidence regarding
128
HPV testing in secondary prevention of cervical cancer. Vaccine 2012;30 Suppl 5: F88-F99.
M AN U
127
129 130
12. Sankaranarayanan R, Nene BM, Shastri SS, Jayant K, Muwonge R, Budukh AM, et al. HPV
131
screening for cervical cancer in Rural India. N Engl J Med 2009;360:1385-94.
132
13. Ronco G, Dillner J, Elfstrom KM, Tunesi S, Snijders PJ, Arbyn M, et al. Efficacy of HPV-
134
based screening for prevention of invasive cervical cancer: follow-up off four European
135
randomised controlled trials. Lancet 2014;383: 524-32.
EP
136
TE D
133
14. Poljak M, Kocjan BJ. Commercially available assays for multiplex detection of alpha human
138
papillomaviruses. Expert Rev Anti Infect Ther 2010;8:1139-62.
139
AC C
137
140
15. Poljak M, Cuzick J, Kocjan BJ, Iftner T, Dillner J, Arbyn M. Nucleic acid tests for the
141
detection of human papillomaviruses. Vaccine 2012;30 (Suppl 5):F100-F106.
142 143
16. Meijer CJLM, Castle PE, Hesselink AT, Franco EL, Ronco G, Arbyn M, Bosch FX, Cuzick J,
144
Dillner J, Heideman DA, Snijders PJ. Guidelines for human papillomavirus DNA test
6
ACCEPTED MANUSCRIPT
145
requirements for primary cervical cancer screening in women 30 years and older. Int J Cancer
146
2009;124:516-20.
147 17. Joura EA, Giuliano AR, Iversen OE, Mehlsen MM, Moreira ED, Ngan Y et al. A 9-valent
149
HPV vaccine against infection and intraepithelial neoplasia in women. N Engl J Med
150
2015;372:711-23.
RI PT
148
SC
151
18. Garland SM, Molesworth EG, Machalek DA, Cornall A, Tabrizi SN. How to best measure the
153
effectiveness of male human papillomavirus vaccine programmes? Clin Microbiol Infect 2015;21
154
(this issue).
M AN U
152
155
19. Isidean SD, Coutlee F, Franco EL. Cobas 4800 HPV Test, a real-time polymerase chain
157
reaction assay for the detection of human papillomavirus in cervical specimens. Expert Rev Mol
158
Diagn 2014;14:5–16.
EP AC C
159
TE D
156
7
