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Is there a place for HPV 16 and 18 viral load quantification in clinical routine practice? The
relationship between high-risk HPV infection (mainly type 16 and 18) and
cervical cancer is now well established1.
Detection of
high-risk HPV has been proposed to optimize cervical cancer screening2
and is now recommended by the American College of Obstetricians and
Gynecologists for the management of patients older than 30 with « Atypical
Squamous Cells of Undetermined Signifiance »3. However,
the clinical interest of high-risk HPV viral load is still debated4-7.
In
a recent publication8, we evaluated the significance of HPV 16
and 18 viral load in women referred to colposcopy. We examined cervical
scrapes obtained at the time of colposcopy from 97 women with an abnormal
cervico-vaginal smear and 54 who were undergoing follow-up after treatment
for a cervical malignancy. HPV 16 and 18 detection and quantification has
been performed using duplex real-time PCR with an in
house plasmidic construct as a standard of quantification. In women between 30 and 40 years old in both groups,
HPV 16 viral loads were significantly higher in high-grade than low-grade
squamous intraepithelial lesions. This was also true of HPV 18 loads in
women of the same age in the initial screening group. However, for younger
women (20 to 30 years old) in the initial screening group, high HPV load
was rarely associated with either high-grade or low-grade squamous
intraepithelial lesions. Moreover, high loads were seen in some of these
patients with proven normal cervix. According
to our findings and experience, quantification of HPV type 16 and 18 viral
load in cervical smears may improve cervical cancer screening. As for HPV
16 or 18 detection, viral load determination must not be used in young
patients but has to be reserved to patients over 30 years old. However,
HPV 16 and 18 quantification tests do not replace colposcopy and are not
sufficient to indicate a cervical treatment. In patients over the age of
30 years, the determination of HPV 16 and 18 viral load brings
complementary information and could improve the sensibility of colposcopy.
Used in a case of abnormal Pap smear or in the follow-up after treatment
for cervical malignancy, a high viral load must lead the physician to pay
particular attention when performing the colposcopy.
Bibliographic
references: 1. Walboomers JM, Jacobs MV, Manos MM, Bosch FX, Kummer JA, Shah KV, et al. Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J Pathol 1999; 189:12-9. 2. Cuzick J, Szarewski A, Cubie H, Hulman G, Kitchener H, Luesley D, et al. Management of women who test positive for high-risk types of human papillomavirus: the HART study. Lancet 2003;362:1871-6. 3. ACOG Practice Bulletin: clinical management guidelines for obstetrician-gynecologists. 2003. Cervical cytology screening. Obstet Gynecol 2003;102:417-27. 4. Ylitalo N, Sorensen P, Josefsson AM, Magnusson PK, Andersen PK, Ponten J, et al. Consistent high viral load of human papillomavirus 16 and risk of cervical carcinoma in situ: a nested case-control study. Lancet 2000;355:2194-8. 5. Josefsson AM, Magnusson PK, Ylitalo N, Sorensen P, Qwarforth-Tubbin P, Andersen PK, et al. Viral load of human papilloma virus 16 as a determinant for development of cervical carcinoma in situ: a nested case-control study. Lancet 2000;355:2189-93. 6. Van Duin M, Snijders PJ, Schrijnemakers HF, Voorhorst FJ, Rozendaal L, Nobbenhuis MA, et al. Human papillomavirus 16 load in normal and abnormal cervical scrapes: an indicator of CIN II/III and viral clearance. Int J Cancer 2002;98:590-5. 7.
Dalstein
V, Riethmuller D, Pretet JL, Le Bail Carval K, Sautiere JL, Carbillet JP,
et al. Persistence and load of high-risk HPV are predictors for
development of high-grade cervical lesions: a longitudinal French cohort
study. Int J Cancer 2003;106:396-403. 8. Carcopino X, Henry M, Benmoura D, Fallabregues AS, Richet H, Boubli L, et al. Determination of HPV type 16 and 18 viral load in cervical smears of women referred to colposcopy. J Med Virol 2006;78:1131-40.
Xavier Carcopino Laboratoire de Virologie, Hopital de la Timone, Marseille, France
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