- Email: [email protected]
HPV genotype replacement: too early to tell
Correspondence
HPV genotype replacement: too early to tell Inge Verdenius and colleagues1 suggest that cross-protection with the human papillomavirus (HPV) vaccine Cervarix might prevent genotype replacement. Some points deserve further discussion. To our knowledge, only one study2 has reported an increase in prevalence of non-vaccine HPV types after vaccination. However, that such increase is induced by vaccination, and thus, that genotype replacement is taking place, is not certain. Nevertheless, we agree that genotype replacement could be happening, because that increase was significant for vaccinated, but not unvaccinated, participants. Yet, the conclusion that genotype replacement is happening in patients vaccinated with Gardasil on the basis of findings from only one study seems premature. Notably, Tabrizi and colleagues’2 findings for Gardasil were not in line with those of Kahn and colleagues,3 because they reported a slight (non-significant) reduction in the prevalence of non-vaccine HPV types in the postvaccination era in Australia (table). Awaited surveillance
Country Age range (years) Vaccine
Tabrizi et al, 20122
Kahn et al, 20123
Australia
USA
18–24
13–26
Gardasil
Gardasil
Prevaccine
202
368
Postvaccine
404
409
≥1 vaccine doses
338 (84%)
242 (59%)
Participants
Recruitment Pre-vaccine period
2005–07
2006–07
Post-vaccine period
2010–11
2009–10
Prevalence of high-risk NVT* Pre-vaccine group
37·6%
47·5%
Post-vaccine vaccinated group
30·8%
65·2%
Difference (post–pre)
–6·8%
+17·7%
NVT=non-vaccine types. *Unadjusted.
Table: Surveillance studies comparing prevalence of HPV types pre-vaccination and post-vaccination
1012
data for the two available vaccines from different settings with varying vaccination coverage should show whether genotype replacement is indeed at work. Verdenius and colleagues’ hypothesis1 followed Malagón and coworkers4 meta-analysis of vaccineinduced cross-protection. However, results of that meta-analysis should be interpreted with caution, because Malagón and coworkers reported significant differences between the two vaccines for persistent infections with HPV types 31 and 45, but not for type 33, for which CIs largely overlapped. Moreover, the two vaccines did not differ for either types 58 and 52, which are both related to type 16 and are largely present in cervical lesions in Asia. 5 The investigators noted that efficacy of Cervarix decreased during follow-up, suggesting waning cross-protection. Overall, if vaccine cross-protection lasts only less than a decade, its beneficial effects, potentially including prevention of genotype replacement, could merely be transitory. Should Verdenius and colleagues’ hypothesis prove true, that Cervarix cross-protection could counterbalance genotype replacement, then two events could happen: HPV types, for which some degree of Cervarix crossprotection has been reported,4 would correspond to those increasing in the population vaccinated with Gardasil;2 or those types would differ, but would somehow interact indirectly through other HPV types. Because Kahn and colleagues2 did not report prevalence data by genotype, whether such HPV-genotype matching happens is unknown. Available data are insufficient to infer that vaccine cross-protection might prevent genotype replacement. To assess vaccination effects on prevalence of non-vaccine HPV types, surveillance studies should provide data by genotype. Such information is essential for disease prevention in
the near future because oncogenic potentials of HPV types differ, and changes in incidence of HPV-related disease are preceded by changes in prevalence of HPV-type infection. We declare that we have no conflicts of interest.
*Margarita Pons-Salort, Anne C M Thiébaut, Didier Guillemot, Michel Favre, Elisabeth Delarocque-Astagneau [email protected] Institut Pasteur, Unité de Pharmacoépidémiologie et Maladies Infectieuses, Paris 75725, France (MP-S, ACMT, DG, ED-A); Pharmaco-épidémiologie et évaluation de l’impact des produits de santé sur les populations (INSERM U657), Paris, France (MP-S, ACMT, DG, ED-A); University Versailles–SaintQuentin-en-Yvelines, Faculté de Médecine Paris Île-de-France Ouest, Garches, France (MP-S, ACMT, DG, ED-A); Assistance publique—Hôpitaux de Paris, Hôpital Raymond-Poincaré, Garches, France (DG); and Institut Pasteur, Centre National de Référence des HPV, Paris, France (MF) 1
2
3
4
5
Verdenius I, Groner JA, Harper DM. Cross protection against HPV might prevent type replacement. Lancet Infect Dis 2013; 13: 195. Tabrizi SN, Brotherton JML, Kaldor JM, et al. Fall in human papillomavirus prevalence following a national vaccination program. J Infect Dis 2012; 206: 1645–51. Kahn JA, Brown DR, Ding L, et al. Vaccinetype human papillomavirus and evidence of herd protection after vaccine introduction. Pediatrics 2012; 130: e249–56. Malagon T, Drolet M, Boily MC, et al. Cross-protective efficacy of two human papillomavirus vaccines: a systematic review and meta-analysis. Lancet Infect Dis 2012; 12: 781–89. Bao YP, Li N, Smith JS, et al. Human papillomavirus type distribution in women from Asia: a meta-analysis. Int J Gynecol Cancer 2008; 18: 71–9.
Procalcitonin as a diagnostic marker for sepsis We read with interest Christina Wacker and colleagues’ systematic review1 of the diagnostic accuracy of procalcitonin as a marker for sepsis. As the investigators stated, the cutoffs for procalcitonin concentration used for discrimination in the primary studies differed substantially between studies. Notably, “some had a cutoff that led to the most favourable results
www.thelancet.com/infection Vol 13 December 2013
HPV genotype replacement: too early to tell Inge Verdenius and colleagues1 suggest that cross-protection with the human papillomavirus (HPV) vaccine Cervarix might prevent genotype replacement. Some points deserve further discussion. To our knowledge, only one study2 has reported an increase in prevalence of non-vaccine HPV types after vaccination. However, that such increase is induced by vaccination, and thus, that genotype replacement is taking place, is not certain. Nevertheless, we agree that genotype replacement could be happening, because that increase was significant for vaccinated, but not unvaccinated, participants. Yet, the conclusion that genotype replacement is happening in patients vaccinated with Gardasil on the basis of findings from only one study seems premature. Notably, Tabrizi and colleagues’2 findings for Gardasil were not in line with those of Kahn and colleagues,3 because they reported a slight (non-significant) reduction in the prevalence of non-vaccine HPV types in the postvaccination era in Australia (table). Awaited surveillance
Country Age range (years) Vaccine
Tabrizi et al, 20122
Kahn et al, 20123
Australia
USA
18–24
13–26
Gardasil
Gardasil
Prevaccine
202
368
Postvaccine
404
409
≥1 vaccine doses
338 (84%)
242 (59%)
Participants
Recruitment Pre-vaccine period
2005–07
2006–07
Post-vaccine period
2010–11
2009–10
Prevalence of high-risk NVT* Pre-vaccine group
37·6%
47·5%
Post-vaccine vaccinated group
30·8%
65·2%
Difference (post–pre)
–6·8%
+17·7%
NVT=non-vaccine types. *Unadjusted.
Table: Surveillance studies comparing prevalence of HPV types pre-vaccination and post-vaccination
1012
data for the two available vaccines from different settings with varying vaccination coverage should show whether genotype replacement is indeed at work. Verdenius and colleagues’ hypothesis1 followed Malagón and coworkers4 meta-analysis of vaccineinduced cross-protection. However, results of that meta-analysis should be interpreted with caution, because Malagón and coworkers reported significant differences between the two vaccines for persistent infections with HPV types 31 and 45, but not for type 33, for which CIs largely overlapped. Moreover, the two vaccines did not differ for either types 58 and 52, which are both related to type 16 and are largely present in cervical lesions in Asia. 5 The investigators noted that efficacy of Cervarix decreased during follow-up, suggesting waning cross-protection. Overall, if vaccine cross-protection lasts only less than a decade, its beneficial effects, potentially including prevention of genotype replacement, could merely be transitory. Should Verdenius and colleagues’ hypothesis prove true, that Cervarix cross-protection could counterbalance genotype replacement, then two events could happen: HPV types, for which some degree of Cervarix crossprotection has been reported,4 would correspond to those increasing in the population vaccinated with Gardasil;2 or those types would differ, but would somehow interact indirectly through other HPV types. Because Kahn and colleagues2 did not report prevalence data by genotype, whether such HPV-genotype matching happens is unknown. Available data are insufficient to infer that vaccine cross-protection might prevent genotype replacement. To assess vaccination effects on prevalence of non-vaccine HPV types, surveillance studies should provide data by genotype. Such information is essential for disease prevention in
the near future because oncogenic potentials of HPV types differ, and changes in incidence of HPV-related disease are preceded by changes in prevalence of HPV-type infection. We declare that we have no conflicts of interest.
*Margarita Pons-Salort, Anne C M Thiébaut, Didier Guillemot, Michel Favre, Elisabeth Delarocque-Astagneau [email protected] Institut Pasteur, Unité de Pharmacoépidémiologie et Maladies Infectieuses, Paris 75725, France (MP-S, ACMT, DG, ED-A); Pharmaco-épidémiologie et évaluation de l’impact des produits de santé sur les populations (INSERM U657), Paris, France (MP-S, ACMT, DG, ED-A); University Versailles–SaintQuentin-en-Yvelines, Faculté de Médecine Paris Île-de-France Ouest, Garches, France (MP-S, ACMT, DG, ED-A); Assistance publique—Hôpitaux de Paris, Hôpital Raymond-Poincaré, Garches, France (DG); and Institut Pasteur, Centre National de Référence des HPV, Paris, France (MF) 1
2
3
4
5
Verdenius I, Groner JA, Harper DM. Cross protection against HPV might prevent type replacement. Lancet Infect Dis 2013; 13: 195. Tabrizi SN, Brotherton JML, Kaldor JM, et al. Fall in human papillomavirus prevalence following a national vaccination program. J Infect Dis 2012; 206: 1645–51. Kahn JA, Brown DR, Ding L, et al. Vaccinetype human papillomavirus and evidence of herd protection after vaccine introduction. Pediatrics 2012; 130: e249–56. Malagon T, Drolet M, Boily MC, et al. Cross-protective efficacy of two human papillomavirus vaccines: a systematic review and meta-analysis. Lancet Infect Dis 2012; 12: 781–89. Bao YP, Li N, Smith JS, et al. Human papillomavirus type distribution in women from Asia: a meta-analysis. Int J Gynecol Cancer 2008; 18: 71–9.
Procalcitonin as a diagnostic marker for sepsis We read with interest Christina Wacker and colleagues’ systematic review1 of the diagnostic accuracy of procalcitonin as a marker for sepsis. As the investigators stated, the cutoffs for procalcitonin concentration used for discrimination in the primary studies differed substantially between studies. Notably, “some had a cutoff that led to the most favourable results
www.thelancet.com/infection Vol 13 December 2013