Therapeutics
HPV vaccination reduced cytologic abnormalities compared with control vaccination in young women
Rodríguez AC, Solomon D, Herrero R, et al; CVT group. Impact of human papillomavirus vaccination on cervical cytology screening, colposcopy, and treatment. Am J Epidemiol. 2013;178:752-60.
Clinical impact ratings: F ★★★★★★✩ I ★★★★★✩✩ Question Does vaccination against human papillomavirus (HPV) types 16 and 18 reduce cytologic abnormalities compared with hepatitis A vaccination in young adult women?
Methods Design: Randomized controlled trial (Costa Rica Vaccine Trial [CVT]). Allocation: {Concealed}*.† Blinding: Blinded† (patients, {health care providers, data collectors, and outcome assessors}‡). Follow-up period: 4 years. Setting: Costa Rica. Participants: 7466 healthy women 18 to 25 years of age {median age 21 y}* who were willing to use contraception during the vaccination period. Exclusion criteria included pregnancy, breastfeeding, chronic disease, previous hepatitis A infection or vaccination, or previous reaction to vaccines. Intervention: Virus-like particle vaccine against HPV types 16 and 18 (Cervarix, GlaxoSmithKline Biologicals) (n = 3726) or hepatitis A control vaccine (n = 3736), {given at enrollment, 1 month, and 6 months}*. Outcomes: Worst cytologic abnormality (high-grade squamous intraepithelial lesion, low-grade squamous intraepithelial lesion, or atypical squamous cells of undetermined significance with a positive reflex Hybrid Capture 2 [HC2] test), colposcopy referral, and treatment with loop electrosurgical excision procedures. Participant follow-up: {93% were followed to study end}‡.
Main results HPV vaccination reduced cytologic abnormalities and had a borderline effect on reducing colposcopy referrals compared with HPV vaccine against HPV types 16 and 18 vs hepatitis A control vaccine in healthy young women§ Outcomes||
HPV Hepatitis A vaccine vaccine
At 4 y RRR (95% CI)
Worst cytologic abnormality excluding enrollment cytology¶ HSIL excluding enrollment cytology¶
32%
5.0%
36%
6.2%
ASC-US/LSIL excluding enrollment cytology¶
27%
30%
Colposcopy referral
29%
31%
Loop electrosurgical excision procedure
5.0%
5.7%
NNT (CI)
11% (5 to 17)
26 (17 to 61)
20% (3 to 35)
80 (42 to 647)
8.9% (2 to 16) 7.9% (−0.45 to 16) 11% (−9 to 28)
38 (21 to 206) ** Not significant
§ASC-US/LSIL = atypical squamous cells of undetermined significance with a positive reflex Hybrid Capture 2 test or low-grade squamous intraepithelial lesion; HPV = human papillomavirus; HSIL = high-grade squamous intraepithelial lesion; other abbreviations defined in Glossary. Event rates, RRR, NNT, and CI for worst cytologic abnormality, HSIL, and ASC-US/LSIL calculated from data provided by the author. ||n = 6586 for cytologic abnormalities and 6844 for other outcomes. ¶Event rates provided by author. **P = 0.03 using the chi-square test. Author reported that RRR CIs were calculated using the score asymptotic approximation.
JC4
© 2013 American College of Physicians
hepatitis A control vaccination; groups did not differ for use of loop electrosurgical excision procedures (Table).
Conclusion HPV vaccination reduced risk for cytologic abnormalities compared with hepatitis A vaccination in young women. *Herrero R, Hildesheim A, Rodríguez AC, et al; Costa Rica Vaccine Trial (CVT) group. Rationale and design of a community-based double-blind randomized clinical trial of HPV 16 and 18 vaccine in Guanacaste, Costa Rica. Vaccine. 2008;26:4795-808. †See Glossary. ‡Information provided by author.
Sources of funding: US National Cancer Institute; Office of Research on Women’s Health, US National Institutes of Health; GlaxoSmithKline Biologicals. For correspondence: Dr. A.C. Rodríguez, INCIENSA Foundation, San José, Costa Rica. E-mail [email protected]. ■
Commentary The study by Rodríguez and colleagues leads to 3 conclusions. First, it adds to the evidence that vaccinating women against HPV reduces cervical neoplasia, including high-grade neoplasia (1). Practitioners who care for adolescent and young adult women should ensure that these patients are offered and encouraged to have HPV vaccination. The subsequent risk for cervical neoplasia will be reduced, and patients will need fewer colposcopies. Second, vaccinating young women before sexual activity is initiated—that is, before they have a chance to become infected with high-risk HPV—works better since the vaccine doesn’t help to eliminate existing infections. In the cohort of women without previous HPV exposure, relative risk reductions with the HPV vaccine were 49% for high-grade squamous intraepithelial lesions and 18% for atypical squamous cells of undetermined significance that were positive for high-risk HPV by HC2 or low-grade squamous intraepithelial lesions (excluding results for enrollment cytology). Finally, and most important, it shows that vaccination cannot replace cervical cancer screening. In the HPV vaccination group, the risk for cervical neoplasia was considerable: Only 63% of women had no cervical abnormalities when screened with Pap testing. In the subgroup of women without previous HPV exposure, this proportion was 80%. But cervical neoplasia occurred despite vaccination, regardless of whether infection was present before vaccination. What are the main messages from the study? 1) Vaccinate adolescent and young adult women against HPV infection. 2) Where possible, do this before they initiate sexual activity. 3) When they reach the age at which initiating screening is recommended— currently 21 years of age in the USA (2)—follow the recently revised guidelines for cytology and HPV testing (2). Brian Budenholzer, MD ECU Brody School of Medicine Greenville, North Carolina, USA References 1. Lehtinen M, Paavonen J, Wheeler CM, et al; HPV PATRICIA Study Group. Lancet Oncol. 2012;13:89−99. 2. Moyer VA, US Preventive Services Task Force. Ann Intern Med. 2012; 156:880-91. 17 December 2013 | ACP Journal Club | Volume 159 • Number 12
Downloaded From: http://annals.org/pdfaccess.ashx?url=/data/journals/aim/929454/ by a University of California San Diego User on 04/26/2017
HPV vaccination reduced cytologic abnormalities compared with control vaccination in young women
Rodríguez AC, Solomon D, Herrero R, et al; CVT group. Impact of human papillomavirus vaccination on cervical cytology screening, colposcopy, and treatment. Am J Epidemiol. 2013;178:752-60.
Clinical impact ratings: F ★★★★★★✩ I ★★★★★✩✩ Question Does vaccination against human papillomavirus (HPV) types 16 and 18 reduce cytologic abnormalities compared with hepatitis A vaccination in young adult women?
Methods Design: Randomized controlled trial (Costa Rica Vaccine Trial [CVT]). Allocation: {Concealed}*.† Blinding: Blinded† (patients, {health care providers, data collectors, and outcome assessors}‡). Follow-up period: 4 years. Setting: Costa Rica. Participants: 7466 healthy women 18 to 25 years of age {median age 21 y}* who were willing to use contraception during the vaccination period. Exclusion criteria included pregnancy, breastfeeding, chronic disease, previous hepatitis A infection or vaccination, or previous reaction to vaccines. Intervention: Virus-like particle vaccine against HPV types 16 and 18 (Cervarix, GlaxoSmithKline Biologicals) (n = 3726) or hepatitis A control vaccine (n = 3736), {given at enrollment, 1 month, and 6 months}*. Outcomes: Worst cytologic abnormality (high-grade squamous intraepithelial lesion, low-grade squamous intraepithelial lesion, or atypical squamous cells of undetermined significance with a positive reflex Hybrid Capture 2 [HC2] test), colposcopy referral, and treatment with loop electrosurgical excision procedures. Participant follow-up: {93% were followed to study end}‡.
Main results HPV vaccination reduced cytologic abnormalities and had a borderline effect on reducing colposcopy referrals compared with HPV vaccine against HPV types 16 and 18 vs hepatitis A control vaccine in healthy young women§ Outcomes||
HPV Hepatitis A vaccine vaccine
At 4 y RRR (95% CI)
Worst cytologic abnormality excluding enrollment cytology¶ HSIL excluding enrollment cytology¶
32%
5.0%
36%
6.2%
ASC-US/LSIL excluding enrollment cytology¶
27%
30%
Colposcopy referral
29%
31%
Loop electrosurgical excision procedure
5.0%
5.7%
NNT (CI)
11% (5 to 17)
26 (17 to 61)
20% (3 to 35)
80 (42 to 647)
8.9% (2 to 16) 7.9% (−0.45 to 16) 11% (−9 to 28)
38 (21 to 206) ** Not significant
§ASC-US/LSIL = atypical squamous cells of undetermined significance with a positive reflex Hybrid Capture 2 test or low-grade squamous intraepithelial lesion; HPV = human papillomavirus; HSIL = high-grade squamous intraepithelial lesion; other abbreviations defined in Glossary. Event rates, RRR, NNT, and CI for worst cytologic abnormality, HSIL, and ASC-US/LSIL calculated from data provided by the author. ||n = 6586 for cytologic abnormalities and 6844 for other outcomes. ¶Event rates provided by author. **P = 0.03 using the chi-square test. Author reported that RRR CIs were calculated using the score asymptotic approximation.
JC4
© 2013 American College of Physicians
hepatitis A control vaccination; groups did not differ for use of loop electrosurgical excision procedures (Table).
Conclusion HPV vaccination reduced risk for cytologic abnormalities compared with hepatitis A vaccination in young women. *Herrero R, Hildesheim A, Rodríguez AC, et al; Costa Rica Vaccine Trial (CVT) group. Rationale and design of a community-based double-blind randomized clinical trial of HPV 16 and 18 vaccine in Guanacaste, Costa Rica. Vaccine. 2008;26:4795-808. †See Glossary. ‡Information provided by author.
Sources of funding: US National Cancer Institute; Office of Research on Women’s Health, US National Institutes of Health; GlaxoSmithKline Biologicals. For correspondence: Dr. A.C. Rodríguez, INCIENSA Foundation, San José, Costa Rica. E-mail [email protected]. ■
Commentary The study by Rodríguez and colleagues leads to 3 conclusions. First, it adds to the evidence that vaccinating women against HPV reduces cervical neoplasia, including high-grade neoplasia (1). Practitioners who care for adolescent and young adult women should ensure that these patients are offered and encouraged to have HPV vaccination. The subsequent risk for cervical neoplasia will be reduced, and patients will need fewer colposcopies. Second, vaccinating young women before sexual activity is initiated—that is, before they have a chance to become infected with high-risk HPV—works better since the vaccine doesn’t help to eliminate existing infections. In the cohort of women without previous HPV exposure, relative risk reductions with the HPV vaccine were 49% for high-grade squamous intraepithelial lesions and 18% for atypical squamous cells of undetermined significance that were positive for high-risk HPV by HC2 or low-grade squamous intraepithelial lesions (excluding results for enrollment cytology). Finally, and most important, it shows that vaccination cannot replace cervical cancer screening. In the HPV vaccination group, the risk for cervical neoplasia was considerable: Only 63% of women had no cervical abnormalities when screened with Pap testing. In the subgroup of women without previous HPV exposure, this proportion was 80%. But cervical neoplasia occurred despite vaccination, regardless of whether infection was present before vaccination. What are the main messages from the study? 1) Vaccinate adolescent and young adult women against HPV infection. 2) Where possible, do this before they initiate sexual activity. 3) When they reach the age at which initiating screening is recommended— currently 21 years of age in the USA (2)—follow the recently revised guidelines for cytology and HPV testing (2). Brian Budenholzer, MD ECU Brody School of Medicine Greenville, North Carolina, USA References 1. Lehtinen M, Paavonen J, Wheeler CM, et al; HPV PATRICIA Study Group. Lancet Oncol. 2012;13:89−99. 2. Moyer VA, US Preventive Services Task Force. Ann Intern Med. 2012; 156:880-91. 17 December 2013 | ACP Journal Club | Volume 159 • Number 12
Downloaded From: http://annals.org/pdfaccess.ashx?url=/data/journals/aim/929454/ by a University of California San Diego User on 04/26/2017
