Human papillomavirus genotype attribution in invasive cervical cancer: a retrospective cross-sectional worldwide study.
BACKGROUND
Knowledge about the distribution of human papillomavirus (HPV) genotypes in invasive cervical cancer is crucial to guide the introduction of prophylactic vaccines. We aimed to provide novel and comprehensive data about the worldwide genotype distribution in patients with invasive cervical cancer.


METHODS
Paraffin-embedded samples of histologically confirmed cases of invasive cervical cancer were collected from 38 countries in Europe, North America, central South America, Africa, Asia, and Oceania. Inclusion criteria were a pathological confirmation of a primary invasive cervical cancer of epithelial origin in the tissue sample selected for analysis of HPV DNA, and information about the year of diagnosis. HPV detection was done by use of PCR with SPF-10 broad-spectrum primers followed by DNA enzyme immunoassay and genotyping with a reverse hybridisation line probe assay. Sequence analysis was done to characterise HPV-positive samples with unknown HPV types. Data analyses included algorithms of multiple infections to estimate type-specific relative contributions.


RESULTS
22,661 paraffin-embedded samples were obtained from 14,249 women. 10,575 cases of invasive cervical cancer were included in the study, and 8977 (85%) of these were positive for HPV DNA. The most common HPV types were 16, 18, 31, 33, 35, 45, 52, and 58 with a combined worldwide relative contribution of 8196 of 8977 (91%, 95% CI 90-92). HPV types 16 and 18 were detected in 6357 of 8977 of cases (71%, 70-72) of invasive cervical cancer. HPV types 16, 18, and 45 were detected in 443 of 470 cases (94%, 92-96) of cervical adenocarcinomas. Unknown HPV types that were identified with sequence analysis were 26, 30, 61, 67, 69, 82, and 91 in 103 (1%) of 8977 cases of invasive cervical cancer. Women with invasive cervical cancers related to HPV types 16, 18, or 45 presented at a younger mean age than did those with other HPV types (50·0 years [49·6-50·4], 48·2 years [47·3-49·2], 46·8 years [46·6-48·1], and 55·5 years [54·9-56·1], respectively).


CONCLUSIONS
To our knowledge, this study is the largest assessment of HPV genotypes to date. HPV types 16, 18, 31, 33, 35, 45, 52, and 58 should be given priority when the cross-protective effects of current vaccines are assessed, and for formulation of recommendations for the use of second-generation polyvalent HPV vaccines. Our results also suggest that type-specific high-risk HPV-DNA-based screening tests and protocols should focus on HPV types 16, 18, and 45.
IDIBELL, Institut Català d'Oncologia-Catalan Institute of Oncology, L'Hospitalet de Llobregat, Barcelona, Spain. s.sanjose@iconcologia.net
Silvia
S
de Sanjose
Wim Gv
WG
Quint
Laia
L
Alemany
Daan T
DT
Geraets
Jo Ellen
JE
Klaustermeier
Belen
B
Lloveras
Sara
S
Tous
Ana
A
Felix
Luis Eduardo
LE
Bravo
Hai-Rim
HR
Shin
Carlos S
CS
Vallejos
Patricia Alonso
PA
de Ruiz
Marcus Aurelho
MA
Lima
Nuria
N
Guimera
Omar
O
Clavero
Maria
M
Alejo
Antonio
A
Llombart-Bosch
Chou
C
Cheng-Yang
Silvio Alejandro
SA
Tatti
Elena
E
Kasamatsu
Ermina
E
Iljazovic
Michael
M
Odida
Rodrigo
R
Prado
Muhieddine
M
Seoud
Magdalena
M
Grce
Alp
A
Usubutun
Asha
A
Jain
Gustavo Adolfo Hernandez
GA
Suarez
Luis Estuardo
LE
Lombardi
Aekunbiola
A
Banjo
Clara
C
Menéndez
Efrén Javier
EJ
Domingo
Julio
J
Velasco
Ashrafun
A
Nessa
Saibua C Bunnag
SC
Chichareon
You Lin
YL
Qiao
Enrique
E
Lerma
Suzanne M
SM
Garland
Toshiyuki
T
Sasagawa
Annabelle
A
Ferrera
Doudja
D
Hammouda
Luciano
L
Mariani
Adela
A
Pelayo
Ivo
I
Steiner
Esther
E
Oliva
Chris Jlm
CJ
Meijer
Waleed Fahad
WF
Al-Jassar
Eugenia
E
Cruz
Thomas C
TC
Wright
Ana
A
Puras
Cecilia Ladines
CL
Llave
Maria
M
Tzardi
Theodoros
T
Agorastos
Victoria
V
Garcia-Barriola
Christine
C
Clavel
Jaume
J
Ordi
Miguel
M
Andújar
Xavier
X
Castellsagué
Gloria I
GI
Sánchez
Andrzej Marcin
AM
Nowakowski
Jacob
J
Bornstein
Nubia
N
Muñoz
F Xavier
FX
Bosch
D000230:Adenocarcinoma / Q000453:epidemiology / Q000473:pathology / Q000517:prevention & control / Q000821:virology*; D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D018196:Carcinoma, Adenosquamous / Q000453:epidemiology / Q000473:pathology / Q000517:prevention & control / Q000821:virology*; D002294:Carcinoma, Squamous Cell / Q000453:epidemiology / Q000473:pathology / Q000517:prevention & control / Q000821:virology*; D003430:Cross-Sectional Studies; D004279:DNA, Viral / Q000302:isolation & purification*; D005260:Female; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D007391:International Cooperation; D016014:Linear Models; D016015:Logistic Models; D008403:Mass Screening / Q000379:methods; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D027383:Papillomaviridae / Q000235:genetics* / Q000276:immunology; D030361:Papillomavirus Infections / Q000453:epidemiology / Q000473:pathology / Q000517:prevention & control / Q000821:virology*; D053918:Papillomavirus Vaccines / Q000627:therapeutic use; D016612:Paraffin Embedding; D016133:Polymerase Chain Reaction; D012189:Retrospective Studies; D002583:Uterine Cervical Neoplasms / Q000453:epidemiology / Q000473:pathology / Q000517:prevention & control / Q000821:virology*; D055815:Young Adult
D004279:DNA, Viral; D053918:Papillomavirus Vaccines