Epidemiological, clinical and viral determinants of the increased prevalence of high-risk human papillomavirus (HPV) infections in elderly women.
BACKGROUND
Population-based studies have reported a second peak of human papillomavirus (HPV) prevalence among women > 55 years, but reasons for this U-shaped HPV prevalence curve are poorly understood.


OBJECTIVE
To analyse determinants of high-risk HPV (HR-HPV) infections among postmenopausal women.


METHODS
A cohort of 3,187 women was stratified into three age categories: i) youngest age group < 25 years (n = 1.103); ii) women between 26-55 years (n = 2.004), and iii) women > 55 years (n = 80), analysed for epidemiological, clinical and virological determinants of their HR-HPV infections. Real-time PCR was used for HPV genotyping, analysis of viral loads for HPV16, 18/45, 31, 33/52/58, 35 and 39, and load of integrated HPV16.


RESULTS
Age-standardised prevalence of HR-HPV infections showed a second peak among women > 55 years, with a perfect U-shaped curve (R2 = 0.966). The factors explaining this increased HR-HPV prevalence among older women include: i) cohort effect, ii) higher viral loads for HR-HPV types with cubic model curve (R2 = 0.714) for HPV 16, iii) distinct shift (p = 0.0001) from multiple-type infections to single HR-HPV types, iv) transition from episomal to integrated HPV16 (p = 0.009), v) higher load of integrated HPV16 (p = 0.009), and, vi) higher proportion of incident infections, higher rate of viral persistence, and lower rate of HR-HPV clearance.


CONCLUSIONS
These data suggest that in women who fail to eradicate their HR-HPV infection until menopause, selection of integrated viral clone has taken place, driving the process towards progressing disease. Consequent to this, most of the HR-HPV infections in women > 55 years were associated with high-grade CIN or invasive carcinoma.
Syrjänen
K
K
Department of Oncology and Radiotherapy, Turku University Hospital, Turku, Finland. kari.syrjanen@tyks.fi
Kulmala
S M
SM
Shabalova
I
I
Petrovichev
N
N
Kozachenko
V
V
Zakharova
T
T
Pajanidi
J
J
Podistov
J
J
Chemeris
G
G
Sozaeva
L
L
Lipova
E
E
Tsidaeva
I
I
Ivanchenko
O
O
Pshepurko
A
A
Zakharenko
S
S
Nerovjna
R
R
Kljukina
L
L
Erokhina
O
O
Branovskaja
M
M
Nikitina
M
M
Grunjberga
V
V
Grunjberg
A
A
Juschenko
A
A
Santopietro
R
R
Cintorino
M
M
Tosi
P
P
Syrjänen
S
S
D000328:Adult; D052685:Alphapapillomavirus / Q000145:classification / Q000235:genetics / Q000472:pathogenicity*; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D015344:DNA Probes, HPV; D005260:Female; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D030361:Papillomavirus Infections / Q000453:epidemiology* / Q000473:pathology; D017698:Postmenopause; D015995:Prevalence; D012426:Russia / Q000453:epidemiology; D012725:Sexual Behavior; D002583:Uterine Cervical Neoplasms / Q000453:epidemiology* / Q000473:pathology / Q000821:virology; D014626:Vaginal Smears; D019562:Viral Load; D002578:Uterine Cervical Dysplasia / Q000453:epidemiology* / Q000473:pathology / Q000821:virology
D015344:DNA Probes, HPV