Primary cervical cancer truly negative for high-risk human papillomavirus is a rare but distinct entity that can affect virgins and young adolescents

Cancer of the uterine cervix is almost exclusively associated with human papillomavirus (HPV). Carcinogenesis is slow, the minimal time from initial HPV infection to invasive carcinoma seems to be less than ten years. In order to identify rapid onset cervical cancer. we carried out a retrospective re-analysis of an extended cohort of patients with invasive cervical cancer, and reviewed cases identified within the cancer registry of Lower Saxony or using Medline or ISI data. No instances of a rapid-onset cancer or true HPV-DNA negative cancer were found among our hospital cohort of 178 women with primary cancer of the uterine cervix. Registry data identified four out of 5,878 patients who were diagnosed with primary cervical cancer at 14 to 20 years of age. The), were classified as clear-cell and endometriod adenocarcinoma and tested persistently negative for high-risk HPV-DNA. Fourteen more cases of cervical cancer in virgins and very young women were identified by a Medline search, mostly with unknown histologic type or rare subtypes of adenocarcinoma. In conclusion, rare adenocarcinoma of the uterine cervix may represent an entity unrelated to HPV, thus explaining instances of rapid onset cervical cancer.

HPV-negative; Cervical cancer rapid onset

[1] Moscicki A.B., Shiboski S., Broering J., Powell K., Clayton L., JayN. et al.: The natural history of human papillomavirus infection as measured by repeated DNA testing in adolescent and young women. J. Pediatr, 1998, 132, 277.

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

[3] Schiffman M.H., Bauer H.M., Hoover R.N., Glass A.G., Cadell.D.M. , Rush B.B. et al.: Epidemiologic evidence showing that human papillomavirus infection causes most cervical intraepithelial neoplasia. J. Natl. Cancer Inst., 1993, 85, 958.

[4] Munoz N., Bosch F.X., de Sanjose S., Tafur L., Izarzugaza I., GiliM. et al.: The causal link between human papillomavirus and invasive cervical cancer: a population-based case-control study in Colombia and Spain. Int. J. Cancer, 1992, 52, 743.

[5] Walboomers J.M., de Roda Husman A.M., Snijders P.J., Stel H.V., Risse E.K., Helmerhorst T.J. et al.: Human papillomavirus in false negative archival cervical smears: implications for screening for cervical cancer. J. Clin. Pathol. , 1995, 48, 728.

[6] Hildesheim A., Hadjimichael O., Schwartz P.E., Wheeler C.M., Barnes W., Lowell D.M. et al.: Risk factors for rapid-onset cervical cancer. Am. J. Obstet. Gynecol. , 1999, 180 (3 Pt 1), 571.

[7] Bohmer G., van den Brule A.J., Brummer O., Meijer C.L., PetryK.U.: No confirmed case of human papillomavirus DNA-negative cervical intraepithelial neoplasia grade 3 or invasive primary cancer of the uterine cervix among 511 patients. Am. J. Obstet. Gynecol. , 2003, 189, 118.

[8] Iftner A., Klug S.J., Garbe C., Blum A., Stancu A., Wilczynski S.P. et al.: The prevalence of human papillomavirus genotypes in nonmelanoma skin cancers of nonimmunosuppressed individuals identifies high-risk genital types as possible risk factors. Cancer Res., 2003, 63, 7515.

[9] Seki H., Takada T., Sodemoto T., Hoshino H., Saitoh K., UekusaT. : A young woman with clear cell adenocarcinoma of the uterine cervix. Int. J. Clin. Oncol. , 2003, 8, 399.

[10] Hanselaar A.G., Van Leusen N.D., De Wilde P.C., Vooijs G.P.: Clear cell adenocarcinoma of the vagina and cervix. A report of the Central Netherlands Registry with emphasis on early detection and prognosis. Cancer, 1991, 67, 1971.

[11] Pirog E.C., Kleter B., Olgac S., Bobkiewicz P., Lindeman J., Quint W.G. et al.: Prevalence of human papillomavirus DNA in different histological subtypes of cervical adenocarcinoma. Am. J Pathol. , 2000, 157, 1055.

[12] Waggoner S.E., Anderson S.M., Van Eyck S., Fuller J., Luce M.C., Herbst A.L.: Human papillomavirus detection and p53 expression in clear-cell adenocarcinoma of the vagina and cervix. Obstet. Gynecol. , 1994, 84, 404.

[13] Cuzick J., Clavel C., Petry K.U., Meijer C.J., Hoyer H., Ratnam S. et al.: Overview of the European and North American studies on HPV testing in primary cervical cancer screening. Int. J. Cancer,2006, 119, 1095

[14] Bowing H.H., McCullough J.A.L.: Carcinoma of the cervix uteri in childhood and adolescence. Am. J. Roentgen, 1941, 45, 819.

[15] Shaw W.F: Carcinoma of the cervix in a girl fifteen years of age.J. Obstet. Gynecol. Br. Emp., 1941, 48, 239.

[16] Stadler G.C.: Cervix carcinoma in a 17 year old virgin. Geburtshilfe Frauenheilk, 1966, 26, 257.

[17] Andrews FJ. , Linehan J.J., Melcher D.H.: Cervical cancer in younger women. Lancet, 1978, 2, 776.

[18] Dekel A., van Iddekinge B., Leiman G.: Invasive squamous carcinoma of the cervix in a 15-year-old girl. A case report and review of the literature. S. Afr. Med. J., 1982, 61, 628.

[19] Palit A., McDowell H., Carty H., Rintala R., Kokai G.: Endometroid adenocarcinoma of the cervix in a 9-year-old girl. Br. J. Radiol. , 1998, 71, 1093.

[20] Graf A.-H. , Pickel H., Hacker G.W., Staudach A.: Invasive adenocarcinoma of the uterine cervix in a 17-year-old girl- a casereport. Geburtsh Frauenheilk, 1998, 58, 620.