Age distribution of human papillomavirus infection and cervical neoplasia reflects caveats of cervical screening policies

Abstract

Although a second age-related peak of human papillomavirus (HPV) infection is observed in many populations, it does not seem to have any impact on cervical screening policies. We examined the age-specific prevalence of HPV infection among 2,604 women enrolled for cervical screening and correlated the age at diagnosis of 2,491 cervical intraepithelial neoplasia Grade 2/3 (CIN2/3) lesions and 801 invasive cervical cancers (ICC). Two peaks of HPV infection were detected at 26-30 and 46-50 years, respectively. The first infection peak was followed by a CIN2/3 peak and an ICC peak at 5-15 and 15 years later, respectively. The second infection peak was followed by an ICC peak 20 years later, but strikingly no CIN2/3 peak was detected in between and thus eliminated an opportunity of treating the lesions at preinvasive stages. The most plausible explanation is that women at the expected second CIN2/3 peak (50-65 years) are not having Pap smears under the current opportunistic screening program. Furthermore, women of this age may have physiological retraction of the transformation zone, and CIN lesions may remain undetected if an adequate Pap smear sample is not obtained. To combat this problem, the screening program in Hong Kong needs to focus on women aged 50 years and older and a mop-up screening up to 75 years is necessary. Bimodal peaks of HPV infection and cervical cancer are seen in many countries and the analysis of populationspecific age distribution of CIN2/3 should be an integral exercise in evaluating the effectiveness of a screening program.Human papillomavirus (HPV) infection is a necessary cause of cervical cancer. 1 The infection is mainly transmitted by the sexual route and occurs most commonly in young sexually active individuals with peak prevalence in women younger than 25 years. 2,3 Interestingly, most studies have also observed a second less pronounced peak of infection among older women, mostly 55 years and older. 2 A few hypotheses have been proposed to explain this observation. First, hormonal changes associated with menopause might induce reactivation of latent HPV infection; however, this second peak has not been universally observed in postmenopausal women. Second, it could be attributed to changes in sexual behavior of women and their partners in middle age, but the occurrence of second peak did not correlate well with data on sexual behavior. 2,3 Finally, the second peak may be a reflection of population-specific cohort effects as it is not consistently observed across the world. 2,4 The underlying reason for this second minor peak is still obscure, and its potential importance has not been fully investigated. It has been shown that a3/a15 HPV types, including HPV61, 71, 72, 81, 83, 84 and 89, are more commonly found in cervical scrape samples collected from older women and these samples also contain more squamous cells. 5 Because a3/a15 HPV types are nononcogenic, the significance of the increased prevalence among older women is unclear. 6 Nonetheless, many studies have confirmed a second ...

Correlates of HPV: a cross-sectional study in women with normal cytology in north-central Morocco

“…In a recent meta-analysis study, De Sanjosé et al reported that HPV prevalence, in women with normal cytology, declines with increasing age, but the authors estimated an increase of HPV infection for women aged 45-52 [28]. This observation was also reported by Chan et al in their recent study where they examined the age-specific prevalence of HPV infection among 2,604 women in Hong Kong [29]. The inverse age dependency has been observed in the Kingdom of Bahrain study where women positive for HPV were significantly older than women negative for HPV [30].…”

“…Women less than 34 years of age had significantly low risk of HPV infection in univariate and multivariate analysis. The literature data regarding the potential relationship between age and HPV infection are conflicting [27][28][29][30]. In a recent meta-analysis study, De Sanjosé et al reported that HPV prevalence, in women with normal cytology, declines with increasing age, but the authors estimated an increase of HPV infection for women aged 45-52 [28].…”

Local immune response in the microenvironment of CIN2–3 with and without spontaneous regression

“…A change in the vaginal flora could also be an interesting cofactor and might be one explanation to the second age-related incidence peak (50-65) observed in many populations. 39 Although negative p16 immunostaining in the superficial layer is slightly more often associated with the non-HPV-16 subtype, most of the non-HPV-16 cases had weak or strong immunostaining in the superficial layer and some HPV-16 high-grade CINs also were negative. Thus, negative p16 in the superficial epithelial layers cannot be used as a definitive indication for non-HPV-16 infection.…”

Cancers attributable to human papillomavirus infection

“…Similar bimodal patterns are seen elsewhere in the developed world and may reflect a cohort effect associated with cervical cancer incidence. 10,11 Other possible explanations for this finding include increasing sexual activity of these older women or their sexual partners, or a decreased age-related immune response, possibly caused by hormonal changes related to menopause that result in a reactivation of latent HPV infection. [12][13][14] Despite the success of the cervical screening program, marked disparities continue to be observed in cervical cancer incidence and mortality between Indigenous and nonIndigenous Australia women.…”