The value of human papillomavirus detection in primary cervical cancer screening

Human papillomavirus (HPV) is present in the vast majority of high-grade gynecological abnormalities (high-grade squamous intraepithelial lesions and worse) and, therefore, HPV detection has a very high negative predictive value. Nevertheless, introduction of HPV detection into primary screening would result in large numbers of false positives: HPV positive women with normal cytology. The prevalence of HPV in women with cytologically normal smears is age-dependent as has been shown extensively. We hypothesize that women at the age of 50, who are HPV negative and have a cytologically normal smear might be encouraged to refrain from further screening. The data available from the literature on HPV prevalence in elderly women is presented. Data of cohort studies of elderly women with and without HPV infection as well as health-economical analyses to investigate the cost-effectiveness of the proposed hypothesis are still lacking.

Cervical cancer; Human papillomavirus; Primary screening

[1] Melchers W., Ferrera A., Willemse D., Galama J., Walboomers J., De Barahona O. et al.: "Human papillomavirus and cervical cancer in Honduran women". Am. J. Trap. Med. Hyg., 1994, 50, 137.

[2] DeBritton R.C., Hildesheim A., De Lao S.L., Brinton L.A., Sathya P., Reeves W.C.: "Human papillomaviruses and other influences on survival from cervical cancer in Panama". Obstet Gynecol., 1993, 81, 19.

[3] Becker T.M., Wheeler C.M., McGough N.S., Jordan S.W., Dorin M., Miller J.: "Cervical papillomavirus infection and cervical dysplasia in hispanic, Native American, and non-hispanic white women in New Mexico". Am. J. Public Health., 1991, 81, 582.

[4] Ngelangel C., Munoz N., Bosch F.X., Limson G.M., Festin M.R., Deacon J. et al.: "Causes of cervical cancer in the Philippines. a case-control study". J. Natl. Cancer Inst., 1998, 90, 43

[5] Chichareon S., Herrero R., Munoz N., Bosch F.X., Jacobs M.V., Deacon J. et al.: "Risk factors for cervical cancer in Thailand: a case-control study". J. Natl. Cancer Inst., 1998, 90, 50.

[6] Chaouki N., Bosch F.X., Munoz N., Meijer CJ., El Gueddari B., El Ghazi A. et al.: "The viral origin of cervical cancer in Rabat Morocco". Int. J. Cance., 1998, 75, 546.

[7] Rolon P.A., Smith J.S., Munoz N., Klug SJ., Herrero R., Bosch X. et al.: "Human papillomavirus infection and invasive cervical cancer in Paraguay". Int J Cancer, 2000, 85, 486.

[8] Herrero R., Hildesheim A., Bratti C., Sherman M. E., Hutchinson M., Morales J. et al.: "Population-based study of human papillomavirus infection and cervical neoplasia in rural Costa Rica". J. Natl. Cancer Inst., 2000, 92, 464.

[9] Lorenzato F., Ho L., Terry G., Singer A., Santos L.C., Batista R.D. et al.: "The Use of human papillomavirus typing in detection of cervical neoplasia in Recife (Brazil)". Int. J. Gynecol. Cancer, 2000, 10, 143.

[10] Baay M.F.D.,T jalma W.A.A.,W eyler J.,G oovaerts G.,B uytaert P.,Y an Marck E.A.E. et al.: "Human papillomavirus infection in the female population of Antwerp, Belgium: Prevalence in healthy women, women with premalignant lesions and cervical cancer" Eur. J. Gynaecol. Oneal., 2001, 22, 204.

[11] Claeys P., Gonzalez C., Gonzalez M., Van Renterghem L., Temmerman M.: "Prevalence and risk factors of sexually transmitted infections and cervical neoplasia in women's health clinics in Nicaragua". Sex Transm. Infect., 2002, 78, 204.

[12] Lo K.W.K., Wong Y.F., Chan M.K. M., Li J. C.B., Poon J.S., Wang Y.W. et al.: "Prevalence of human papillomavirus in cervical cancer: A multicenter study in China". Int. J. Cancer, 2002, 100, 327.

[13] Molano M., van den Brule A.J.C., Posso H., Weiderpass E., Ronderos M., F ranceschi S. et al.: "Low grade squamous intra-epithelial lesions and human papillomavirus infection in colombian women". Br. J. Cancer, 2002, 87, 1417.

[14] Walboomers J.M.M., Jacobs M.Y., Manos M.M., Bosch F.X., Kummer J.A., Shah K.Y. et al.: "Human papillomavirus is a necessary cause of invasive cervical cancer worldwide". J. Pathol., 1999, 189, 12.

[15] Munoz N., Bosch F.X., de Sanjose S., Herrero R., Castellsague X., Shah K.Y. et al.: "Epidemiologic classification of human papillomavirus types associated with cervical cancer". N. Engl. J. Med., 2003, 348, 518.

[16] Cason J., Best J.M., Raju K.S.: "Vertical transmission of human papillomaviruses". Am. J. Obstet. Gynecol., 1999, 180, 774.

[17] Kjaer S.K, Chackerian B., van den Brule A.J., Svare E.I., Paull G., Walbomers J.M. et al.: "High-risk human papillomavirus is sexually transmitted: Evidence from a follow-up study of virgins starting sexual activity (intercourse)". Cancer Epidemiol Biomarkers Prev,.，2001, 10, 101.

[18] Thomas D.B., Ray R.M., Kuypers J., Kiviat N., Koetsawang A., Ashley R.L. et al.: "Human papillomaviruses and cervical cancer in Bangkok. III. T he role of husbands and commercial sex workers". Am. J. Epidemiol., 2001, 153, 740.

[19] Baay M., Lardon F., Vermorken J.B., Verhoeven V., Avonts D., Yan Royen P. et al.: "HPV in cervix and vagina (Letter)". Sex Transm. Infect., 2004, 80, 249.

[20] Melkert P.W., Hopman E., van den Brule A.J., Risse E.K., van Diest P.J., Bleker O.P. et al.: "Prevalence of HPY in cytomorphologically normal cervical smears, as determined by the polymerase chain reaction, is age-dependent". Int. J. Cancer, 1993, 53, 919.

[21] Cuzick J., Szarewski A., Terry G., Ho L., Hanby A., Maddox P. et al.: "Human papillomavirus testing in primary cervical screening". Lancet, 1995, 345, 1533.

[22] Burk R.D.,K elly P.,F eldman J.,B romberg J.,V ermund S.H.,D eHovitz J.A. et al.: "Declining prevalence of cervicovaginal human papillomavirus infection with age is independent of other risk factors". Sex Transm Dis., 1996, 23, 333.

[23] de Roda Husman A.M., Walboomers J.M., Hopman E., Bieker O.P., Helmerhorst T.M., Rozendaal L. et al.: "HPV prevalence in cytomorphologically normal cervical scrapes of pregnant women as determined by PCR: the age-related pattern". J. Med. Viral., 1995, 46, 97.

[24] Morrison E.A., Ho G.Y., Yermund S.H., Goldberg G.L., Kadish A.S., Kelley K.F. et al.: "Human papillomavirus infection and other risk factors for cervical neoplasia: a case-control study". Int. J. Cancer, 1991, 49, 6.

[25] Cuzick J., Beverley E., Ho L., Terry G., Sapper H., Mielzynska I. et al.: "HPY testing in primary screening of older women". Br. J. Cancer, 1999, 81, 554.

[26] Clavel C., Bory J.P., Rihet S., Masure M., Duval Binninger I., Putaud I. et al.: "Comparative analysis of human papillomavirus detection by hybrid capture assay and routine cytologic screening to detect high-grade cervical lesions". Int. J. Cancer, 1998, 75, 525.

[27] Munoz N., Kato I., Bosch F.X., Eluf Neto J., De Sanjose S., Ascunce N. et al.: "Risk factors for HPY DNA detection in middleaged women". Sex Transm. Dis., 1996, 23, 504.

[28] Baay M.F.D., K」etland E.F., Ndhlovu P.D., Deschoolmeester Y., Mduluza T., Gomo E. et al.: "Human papillomavirus in a rural community in Zimbabwe: the impact of HIV co-infection on HPV genotype distribution". J. Med. Viral., 2004, 73, 48.

[29] Koutsky L.: "Epidemiology of genital human pap仆lomavirus infection". Am. J. Med., 1997, 102, 3.

[30] Ho G.Y., Bierman R., Beardsley L., Chang C. J., Burk R.D.: "Natural history of cervicovaginal papillomavirus infection in young women". N. Engl. J. Med., 1998, 338, 423.

[31] Woodman C.B, Collins S., Winter H., Bailey A., Ellis J., Prior P. et al.: "Natural history of cervical human papillomavirus infection in young women: a longitudinal cohort study". Lancet., 2001, 357, 1831.

[32] Nobbenhuis M.A.E., Walboomers J.M.M., Helmerhorst T.J.M., Rozendaal L., Remmink A.J., Risse E.K.J. et al.: "Relation of human papillomavirus status to cervical lesions and consequences for cervical-cancer screening: a prospective study". Lancet., 1999, 354, 20.

[33] Koutsky L.A., Ault K.A., Wheeler C.M., Brown D.R., Barr E., Alvarez F.B. et al.: "A controlled trial of a human papillomavirus type 16 vaccine". New Engl. J. Med., 2002, 347, 1645.

[34] Sanders G.D.,Taira A.V.: "Cost effectiveness of a potential vaccine for human papillomavirus". Emerg. Infect. Dis., 2003, 9, 37.

[35] Kulasingam S.L.,Myers E.R.: "Potential health and economic impact of adding a human papillomavirus vaccine to screening programs". JAMA, 2003, 290, 781.

[36] Follen M., Meyskens F.L., Alvarez R.D., Walker J.L., Bell M.C., Storthz K.A. et al.: "Cervical cancer chemoprevention, vaccines, and surrogate endpoint biomarkers". Cancer, 2003, 98, 2044.

[37] Kotecha M.T., Afghan R.K., Vasilikopoulou E., Wilson E., Marsh P., Kast W.M. et al.: "Enhanced tumour growth after DNA vaccination against human papilloma virus E7 oncoprotein: Evidence for tumour-induced immune deviation". Vaccine, 2003, 21, 2506.

[38] T he ASCUS-LSIL Triage Study (ALTS) Group: "Results of a randomized trial on the management of cytology interpretations of atypical squamous cells of undetermined significance". Am. J. Obstet. Gynecol., 2003, 188, 1383.

[39] The ASCUS-LSIL Triage Study (ALTS) Group: "A randomized trial on the management of low-grade squamous intraepithelial lesion cytology interpretations". Am. J. Obstet. Gynecol., 2003, 188, 1393.

[40] Arbyn M., Buntinx F., Van Ranst M., Paraskevaidis E., Martin-Hirsch P., Dillner J.: "Virologic versus cytologic triage of women with equivocal Pap smears: a meta-analysis of the accuracy to detect high-grade intraepithelial neoplasia". J. Natl. Cancer Inst., 2004, 96, 280.

[41] Petry K.U., Menton S., Menton M., van Loenen Frosch F., Gomes H.D., Holz B. et al.: "Inclusion of HPV testing in routine cervical cancer screening for women above 29 years in Germany: Results for 8466 patients". Br. J. Cancer, 2003, 88, 1570.

[42] Ratnam S., Franco E.L, Ferenczy A.: "Human papillomavirus testing for primary screening of cervical cancer precursors". Cancer Epidemiol. Biomarkers Prev., 2000, 9, 945.

[43] Kjellberg L., Wiklund F., Sjoberg I., Wadell G., Angstrom T., Dillner J. et al.: "A population-based study of human papillomavirus deoxyribonucleic acid testing for predicting cervical intraepithelial neoplasia". Am. J. Obstet. Gynecol., 1998, 179, 1497.

[44] Van Wijngaarden W.J., Duncan I.D.: "Rationale for stopping cervical screening in women over 50". Br. Med. J., 1993, 306, 967.

[45] van Wijngaarden W.J. ,Duncan I.D.: "Upper age limit for cervical screening". Br. Med. J., 1993, 306, 1409.

[46] Sherlaw Johnson C., Gallivan S., Jenkins D.: "Withdrawing low-risk women from cervical screening programmes: Mathematical modelling study". Br. Med. J., 1999, 318, 356.

[47] Cruickshank M.E., Angus V., Kelly M., McPhee S., Kitchener H.C.: " T he case for stopping cervical screening at age 50". Br. J. Obstet. Gynaecol., 1997, 104, 586.

[48] Baay M.F., Weyler J., Baekelandt M., Buytaert P., Van Marck E.A., Goossens H. et al.: "Cervical cancer and the human papillomavirus: the possible role of molecular HPV detection (in Dutch)". Tijdschr Geneesk., 2001, 57, 1097.

[49] Sell ors J.W., Karwalajtys T.A., Kaczorowski J.A., Mahony J.B., Lytwyn A., Chong S. et al.: "Prevalence of infection with carcinogenic human papillomavirus among older women". Can. Med. Assoc. J., 2002, 167, 871.

[50] Baay M.F.D., Smits E., Tjalma W.A.A., Lardon F., Weyler J., Van Royen P. et al.: "Can cervical cancer screening be stopped at 50: the prevalence of HPV in elderly women". Int. J. Cancer, 2004, 108, 258.

[51] Cruickshank M.E., Chambers G., Murray G., McKenzie L., Donaldson C., Andrew J. et al.: "Age-restricted cervical screening: HPV testing at age 50 identifies a high risk group for cervical disease". Int. J. Gynecol. Cancer, 2002, 12, 735.