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.
de Sanjose
Silvia
S
IDIBELL, Institut Català d'Oncologia-Catalan Institute of Oncology, L'Hospitalet de Llobregat, Barcelona, Spain. s.sanjose@iconcologia.net
Quint
Wim Gv
WG
Alemany
Laia
L
Geraets
Daan T
DT
Klaustermeier
Jo Ellen
JE
Lloveras
Belen
B
Tous
Sara
S
Felix
Ana
A
Bravo
Luis Eduardo
LE
Shin
Hai-Rim
HR
Vallejos
Carlos S
CS
de Ruiz
Patricia Alonso
PA
Lima
Marcus Aurelho
MA
Guimera
Nuria
N
Clavero
Omar
O
Alejo
Maria
M
Llombart-Bosch
Antonio
A
Cheng-Yang
Chou
C
Tatti
Silvio Alejandro
SA
Kasamatsu
Elena
E
Iljazovic
Ermina
E
Odida
Michael
M
Prado
Rodrigo
R
Seoud
Muhieddine
M
Grce
Magdalena
M
Usubutun
Alp
A
Jain
Asha
A
Suarez
Gustavo Adolfo Hernandez
GA
Lombardi
Luis Estuardo
LE
Banjo
Aekunbiola
A
Menéndez
Clara
C
Domingo
Efrén Javier
EJ
Velasco
Julio
J
Nessa
Ashrafun
A
Chichareon
Saibua C Bunnag
SC
Qiao
You Lin
YL
Lerma
Enrique
E
Garland
Suzanne M
SM
Sasagawa
Toshiyuki
T
Ferrera
Annabelle
A
Hammouda
Doudja
D
Mariani
Luciano
L
Pelayo
Adela
A
Steiner
Ivo
I
Oliva
Esther
E
Meijer
Chris Jlm
CJ
Al-Jassar
Waleed Fahad
WF
Cruz
Eugenia
E
Wright
Thomas C
TC
Puras
Ana
A
Llave
Cecilia Ladines
CL
Tzardi
Maria
M
Agorastos
Theodoros
T
Garcia-Barriola
Victoria
V
Clavel
Christine
C
Ordi
Jaume
J
Andújar
Miguel
M
Castellsagué
Xavier
X
Sánchez
Gloria I
GI
Nowakowski
Andrzej Marcin
AM
Bornstein
Jacob
J
Muñoz
Nubia
N
Bosch
F Xavier
FX
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