Human papillomavirus infection and other risk factors for cervical intraepithelial neoplasia in Japan

Abstract

It is widely accepted that human papillomavirus (HPV) is the primary causative agent of cervical neoplasia (cervical intraepi thelial neoplasia [CIN] and invasive cancer) (zur Hausen, 1991). However, HPV infection of the uterine cervix does not always induce cellular abnormalities (de Villiers et al, 1987), suggesting that other factors play a role in the development of cervical neoplasia. Many epidemiologic factors have been suggested as relevant to the development of cervical neoplasia (Rotkin, 1973;Bornstein et al, 1995). We conducted a case-control study to clarify how epidemiologic factors are involved in the development of CIN in relation to HPV infection. MATERIALS AND METHODS Study populationThe study population consisted of women aged 55 or younger who underwent Papanicolaou test screening at nine hospitals between June 1995 and July 1996. For women with abnormal cervical cytology, colposcopically directed biopsies were performed. The cases enrolled in the study were women in whom CIN was first detected during the study period. A total of 167 women who had histological evidence of CIN were included; low-grade CIN (CIN I [n ϭ 94]) and high-grade CIN (CIN II [n ϭ 40] and CIN III [n ϭ 33]). We excluded carcinoma in situ from CIN III. The histological review was performed by one experienced pathologist (KN). Controls matched one-to-one with cases on age (within 5 years) and hospital were selected from subjects who were found to have normal cervical cytology. All CIN cases and controls gave written informed consent. The questionnaireInformation concerning health issues related to the possible aetiology of CIN was obtained by a self-administered questionnaire. The questionnaire, which included demographic factors, smoking habits, contraceptive and reproductive history, and sexual behaviour, was distributed to each case or control on their second hospital visit. Several participants gave no answers to certain questions. Detection and typing of HPVCellular DNA was extracted from cervical exfoliated cells by standard procedure. We used the consensus L1 primers, L1C1 (1 µM), L1C2 (0.5 µM) and L1C2M (0.5 µM), for the polymerase chain reaction (PCR) (Yoshikawa et al, 1991). HPV types were identified on the basis of the restriction fragment length polymorphism. The assay can type at least 26 genital HPVs. HPV data were not obtained from nine (5%) of CIN cases and 37 (22%) of controls. HPV types were categorized into three groups of carcinogenic potency according to then risk classification proposed by Lorincz et al, (1992); i.e. high-, intermediate-and low-risk HPVs (Table 1). Blood sampling and serum antibody detectionA blood sample for serological assays of herpes simplex virus (HSV), cytomegalovirus (CMV) and Chlamydia trachomatis (CT) was collected from each subject. Blood sampling was not available in 9 (5%) CIN cases and 5 (3%) controls. Antibodies were assayed by using commercially available enzyme-linked immunosorbent assay (ELISA) kits; HSV and CMV (Denkaseiken, Niigata, Japan), and CT (Labsystems Oy, Hels...

Are smoking and chlamydial infection risk factors for CIN? Different results after adjustment for HPV DNA and antibodies

“…The estimated risks for CIN development in relation to various epidemiological factors are shown in Table 3. In the present study, the adjusted analysis for HPV DNA alone gave the same results as our previous study (Yoshikawa et al, 1999). Marriage, multiparity and age at first pregnancy were found to be significant risk factors for CIN development in the crude and adjusted analyses.…”

“…The details about this case -control study have been provided elsewhere (Yoshikawa et al, 1999). Among a total of 167 pairs, serum samples from 26 cases and 58 controls were not available for HPV capsid serology.…”

“…The distributions of study variables in the excluded/included cases and controls were similar. We examined HPV DNA in cervical samples by polymerase chain reaction (PCR) using consensus primers for the HPV L1 region (Yoshikawa et al, 1999). Detection of IgG antibodies to HPV16, 52 and 58, the most frequently detected HPV types in Japan, was performed by enzyme-linked immunosorbent assay (ELISA) using purified L1-capsids (virus-like particles (VLPs)) as antigens (Matsumoto et al, 2003).…”

Incidence risk of cervical intraepithelial neoplasia 3 or more severe lesions is a function of human papillomavirus genotypes and severity of cytological and histological abnormalities in adult Japanese women

“…A low detection rate of these two types of HPV has been previously reported in Japanese women. The reported HPV18 detection rate was 0%, 28 in high-grade CIN/HSIL. Therefore, our HPV type-specific detection rates correspond with those of previous studies.…”

Cervical Cytologic Examination During Physical Checkup of Pregnant Women: Cervical Cancer Screening in Women Under the Age of Thirty

“…For example, according to reports from the Miyagi Prefecture Cancer Registry, the ageadjusted morbidity rate for intraepithelial carcinoma in women under 30 has increased over the last 20 years from 0.4 to 3.3 per 100 000 women. Much research has identified that occurrence of cervical cancer is attributable to infection of the uterine cervix with human papillomavirus (HPV), and this infection route is known to be associated with sexual behavior (Yaegashi et al 1989;Anttila et al 1999;Yoshikawa et al 1999;Woodman et al 2001). It seems that recent changes in sexual behavior, such as decrease in age of first intercourse and an increase in the number of sexual partners, result in the spread of HPV infection among young women and lead to an increase in the cervical cancer morbidity rate among young people (Anttila et al 1999).…”