Assessing the feasibility of single lifetime PAP smear evaluation between 41-50 years of age as strategy for cervical cancer control in developing countries from our 32 years of experience of hospital-based routine cytological screening

In view of the huge expenditure involved in mass cytological screening as well as lack of cytology manpower in the developing countries, single lifetime screening at 45 yr of age has been suggested as feasible strategy for control of cervical cancer. The present study is aimed at testing this hypothesis in a broader prospective, accommodating women between 41 and 50 yr of age from the data derived from the ongoing long-term hospital-based routine cervicovaginal cytology at Queen Mary's Hospital, Lucknow, India. The cervical smears of 31,032 women have been evaluated cytologically during a span of 32 yr (April 1971-March 2003) for early detection of carcinoma cervix and sexually transmitted diseases (STDs). The incidence of squamous intraepithelial lesions (SIL) was found to be 6.1% while frank malignancy was seen in 0.5% of cases. The following observations were made from the accumulated cytological data: (a) approximately 30% of the total cancer cases was in the age group of 41-50 yr; (b) the maximum number of SIL cases was detected in women between 41 and 50 yr of age (35% of the total SIL cases), and adequate management of these SIL cases would prevent cancer cases from occurring in later years, thus minimizing the maximum incidence of 1.3% observed in women beyond 50 yr of age; (c) the incidence of human papillomavirus (HPV) infection also was found quite high in women between 41 and 50 yr old, the adequate management of which would prevent onset/progression of any premalignant changes in the cervix. Our experience of 32 yr of cytological screening substantiates the hypothesis of single lifetime screening between 41 and 50 yr of age as an effective strategy for control of carcinoma cervix in developing countries like ours.     

Results of clinically downstaging cervical cancer in a cytological screening programme

The study was aimed at clinically downstaging cancer of the cervix during a cytological Screening Programme to find out whether such a strategy may help in yielding a large number of early cases of cancer. A cohort of 6,178 women with different cervical lesions were cytologically examined from April 1971 at Queen Mary's Hospital, Lucknow, India. The 8,718 asymptomatic women with healthy cervices were taken as controls. The incidence of cervical dysplasia and malignancy in the study group was found to be 11.2% and 1.9%, which was statistically highly significant compared to control values of 3.3% and 0.02%, respectively. Dysplastic smears were seen maximally in women whose cervix bled to the touch, and the rate of cervical cancer was high in women with suspicious cervix. Dysplastic smears were seen frequently in all age and parity groups, but malignancy was common in women of high age (over 30 years) and high parity (two and above). The incidence of three sexually transmitted diseases, namely Trichomonas vaginalis, Herpes simplex, and condyloma revealed highly significant values, especially in women whose cervix bled to the touch. The study highlights the strategy of clinically downstaging cervical cancer, which is very useful in detecting a large number of dysplasia and frank malignancy cases and also the presence of any associated sexually transmitted pathogens whose treatment would aid in restricting the rising incidence of the dreaded disease in this country. Diagn. Cytopathol. 1998;19:344–348. © 1998 Wiley-Liss, Inc.     

Contribution of HPV sequences detection in cervical carcinoma screening

At the present time, Human Papillomaviruses (HPV) is a leading cause of squamous intraepithelial lesions (SIL) and invasive carcinoma of the cervix. The aim of this article was to review the main taxonomic and epidemiologic data on HPV infection and to assess the potential clinical implications of the different HPV tests in staging women with borderline cytologies (ASC-US; ASC-H; LSIL); for follow-up after treatment of high-grade cervical intraepithelial neoplasia (CIN), for primary screening as the sole screening modality, or in association with cytology.     

Anal cytology: Is there a role for reflex HPV DNA testing?

There is an increased incidence of anal squamous carcinoma and its precursor lesions (anal intraepithelial neoplasia [AIN]) among persons who engage in anal-receptive sex. Analogous to cervical cancer screening, anal Papanicplaou (Pap) smears currently are used to screen these high-risk populations. Human papilloma virus (HPV) has been implicated in anal carcinoma pathogenesis and this study was performed to assess the potential role of HPV DNA testing as an adjunct to anal cytology. We correlated cytological diagnoses and HPV DNA (Digene Hybrid Capture [HC II] assay) in anal specimens collected in SurePath liquid medium from 118 patients; 54.8% of cases diagnosed as atypical squamous cells of undetermined significance (ASC-US) and 87.8% diagnosed as low-grade squamous intraepithelial lesion (LSIL) or above tested positive for high- risk HPV DNA (B+). High-grade SIL (HSIL) was present in 31 of the 51 patients with follow-up. Although a cytological diagnosis of ASC-US or above was a reliable indicator for AIN, cytology frequently did not accurately predict the grade of SIL in subsequent biopsy. Our findings suggest that reflex HPV DNA testing would be helpful in triaging patients diagnosed with ASC-US. However, patients diagnosed with LSIL or above should go directly to ansocopic biopsy.     

Squamous intraepithelial lesions in cervical smears of human immunodeficiency virus-seropositive adolescents

Various authors have reported a high rate of human papillomavirus (HPV) infection and HPV-related neoplasias in human immunodeficiency virus (HIV)-seropositive women. On the other hand, young women are most susceptible to cervical infection because of immaturity of the cervix, as it appears that HPV has more access to the basal cells of the differentiating epithelium. The purpose of the present work was to study cervical smears of 82 adolescent HIV-seropositive women (13–21 years of age) to search for cytological evidence of cervical intraepithelial neoplasias. Twenty-one cases showed characteristic features of HPV infection and squamous intraepithelial lesions (SIL; 25.6%). Sixteen cases aged from 17 to 21 years (mean age 19.5 years) had low-grade SIL (LSIL; 19.5%) and five cases aged from 18 to 21 years (mean age 20.2 years) had high-grade SIL (HSIL; 6.1%). There was no significant difference between the mean age of patients with LSIL and HSIL. Two cases had atypical squamous cells of undetermined significance (ASCUS). In the present work it was found that HIV-seropositive adolescents have a high risk for preneoplastic lesions of the cervix (25.6%) as well as a high incidence of more aggressive lesions (6.1% of HSIL) when compared to the general population of adolescents. As it can be assumed that, if the age of acquisition of the infection in both groups (in the general population and HIV-seropositive women) is the same, it is probable that HIV infection in adolescents not only increases the frequency of HPV infections but also facilitates the evolution to more aggressive preneoplastic lesions of the cervix due to HPV. Diagn. Cytopathol. 1998;18:91–92. © 1998 Wiley-Liss, Inc.     

Role of different etiological factors in progression of cervical intraepithelial neoplasia

Implication of high risk-human Papillomavirus in the process of cervical carcinogenesis is well documented. However, carcinogenesis in the cervix is recognized as multifactorial and other unknown etiological factors are also presumed to contribute to development of cancer. The present communication was aimed to investigate the role of risk factors such as age, parity, cervical lesions, and gynecological symptoms in the progression of the intra-epithelial cervical neoplasia. The study followed 571 cytologically diagnosed cases of high-grade squamous intraepithelial lesions (HSIL) during 35 yr of cytological screening, which is in progress at Gynae OPD of Queen Mary's Hospital of the University since April 1971 and until June 2005, a total of 33,658 cervical smears have been cytologically evaluated. Analysis of different risk factors in 571 HSIL cases revealed high parity coupled with increasing age to play a significant role in the progression of SIL. Further aggravated cervical lesions such as suspicious and unhealthy cervix and persistent vaginal discharge were found to be contributing factor in the progression of SIL. All these factors were predominantly seen in 35 cases of severe dysplasia that have shown progression from moderate dysplasia. The study indicates that women of high parity, especially with high age, are more prone to progression of SIL and hence this group needs mandatory cytological evaluation. Further adequate treatment of mild cervical lesions and persistent vaginal discharge is necessary to avoid the aggravation of the lesion/symptom and subsequent progression of dysplasia.     

Role of socio-economic factors and cytology in cervical erosion in reproductive age group women

A cross-sectional study involving 357 females in the reproductive age group (15-44) was conducted in an urban community of Nagpur with the objective of studying the role of socio-economic factors & cytology in cervical erosion. Cervical erosion was detected in 82 (22.96%) females. Out of these mild dysplasia was seen in 9.75% females & moderate dysplasia in 2.43% females. High percentages of inflammatory smears i.e. (75.68%) were obtained in women with cervical erosion. Cervical erosion was more common in illiterate & women with low literacy status as compared to women with higher education. Majority of cases of cervical erosion (75.6%) were detected in women with high parity. A statistically significant association was found between lower socio-economic status, early age at marriage & ocurrence of cervical erosion (p<0.001 & p<0.01 respectively). The study concludes that socio-economic factors such as illiteracy and low literacy status, lower socio-economic status, early age at marriage and high parity are contributory for the occurrence of cervical erosion and regular cytological screening by Pap smear will help in early detection of carcinoma cervix and thereby reduce the morbidity and mortality caused by the same.     

Cervical cytology findings in women infected with the human immunodeficiency virus

It has been suggested that immunocompromised, HIV-infected patients are at risk of developing HPV infection and SIL. The well documented role of HPV and SIL in cervical carcinogenesis should lead to frequent, careful evaluation of HIV infected women. Forty-four cervical smears from 23 patients (20 HIV and 3 AIDS) were reviewed. While 11 of the 23 patients produced negative smears, 11 had abnormal cytological findings on at least one occasion. Sixteen smears (36 percent) from 10 patients (43%) showed evidence of HPV and/or SIL Two smears (two patients) were assigned to the benign epithelial atypia category. (One of these showed keratosis which may indicate HPV infection.) Six smears (three patients) represented either a severe Trichomonas, fungal (Candida sp.), or Herpes infection. Three smears were deemed unsatisfactory for diagnosis due to severe acute inflammation or obscuring blood. Five biopsies were available. In four, histologic findings supported the original cytologic diagnosis. One patient with a negative smear had a biopsy showing condyloma. This study further supports an association of HPV and/or cervical dysplasia with HIV. Careful evaluation and follow-up of HIV-infected women is essential.     

Papillomavirus and cervical cancer: a clinical and laboratory study

It is now widely accepted that HPV types 16, 18, 31, and 33 are associated with the development of high grade intraepithelial neoplasia and malignant lesions in the cervix. On this basis, the identification of HPV types in cervical scrape samples has been advocated as a supplement to cytological screening tests. However, little is known of the distribution of the virus at different sites in the lower female genital tract or of how this distribution may change during the natural course of HPV infection. In this survey, HPV DNA dot hybridizations and, in some instances, Southern blot hybridizations with mixed HPV 6/11 and 16/18 probes were undertaken to detect HPV DNA in cervical scrapes and biopsies of the cervix, vagina, and vulva. A total of 92 women attending a Sydney hospital were screened: 59 of these patients had cervical disease, either invasive cervical carcinoma (CaCx) or cervical intraepithelial neoplasia (CIN), grades I-III. A group of 33 women who lacked evidence of cervical abnormalities served as controls. HPV DNA, predominantly type 16/18, was detected in the cervical biopsies of 96% of the CaCx patients, 80% of the CIN III patients, and 65% of the CIN I-II patients. In contrast only 9% of the cervical biopsies from the control group contained detectable HPV 6, 11, 16, or 18 DNA. A high proportion of the women with cervical abnormalities had evidence of concurrent vaginal and/or vulval papillomavirus involvement. The significance of these findings for routine screening and subsequent management of patients with HPV-associated cervical disease is discussed.     

Use of anticontamination primers in the polymerase chain reaction for the detection of human papilloma virus genotypes in cervical scrapes and biopsies

A reliable application of the polymerase chain reaction (PCR) for detection of the human papilloma virus (HPV) genotypes in cervical smears and biopsies was developed. Primers flanking the HPV cloning site were used to avoid detection of cloned HPV plasmids. These anticontamination primers were used for the specific detection of HPV 6, 11, 16, 18, and 33 in cervical scrapes that had been tested previously for HPV with a combined modified filter in situ hybridization (modified FISH) and dot blotting procedure. The PCR appeared to be superior. Two groups of women were screened for HPV genotypes. Group A consisted of women belonging to a regularly screened population, and group B contained women attending a gynaecological clinic. It appeared that the overall prevalence of HPV in cytologically normal scrapes in the first group was 6%, whereas in the second group 12% was found. In scrapes with cytological dysplasia, the prevalence of HPV in group A and B was approximately 40% and 60%, respectively. HPV 16 was present predominantly. In biopsies of squamous cell carcinomas of the cervix uteri, an HPV prevalence rate of 90% was found, all of which contained only HPV 16 and 18. These data indicate an important role for HPV detection in the screening of cervical scrapes to identify women with an increased risk of cervical cancer.     

Epidemiology of cervical cancer in Colombia

Worldwide, cervical cancer is the third most common cancer in women, and the first or second most common in developing countries. Cervical cancer remains in Colombia the first cause of cancer mortality and the second cause of cancer incidence among women, despite the existence of screening programs during the last 3 decades. Bucaramanga, Manizales and Cali reported rates around 20 per 100,000and Pasto 27 per 100,000. The Cali cancer registry has reported a progressive decrease in the age standardized incidence and mortality rates of cervical cancer over the past 40 years. Reasons for the decline in incidence and mortality of cervical cancer are multiple and probably include: improvement in socio-economic conditions, decrease in parity rates and some effect of screening programs. Human papilloma Virus is the main cause of cervical cancer, HPV natural history studies have now revealed that HPVs are the commonest of the sexually transmitted infections in most populations. Most HPV exposures result in spontaneous clearance without clinical manifestations and only a small fraction of the infected persons, known as chronic or persistent carriers, will retain the virus and progress to precancerous and cancer. HPV 16 and 18 account for 70% of cervical cancer and the 8 most common types. (HPV 16, 18, 45, 33, 31, 52, 58 and 35) account for about 90% of cervical cancer. Case-control studies also allowed the identification of the following cofactors that acting together with HPV increase the risk of progression from HPV persistent infection to cervical cancer: tobacco, high parity, long term use of oral contraceptives and past infections with herpes simplex type 2 and Chlamydia trachomatis. The demonstration that infection with certain types of human papillomavirus (HPV) is not only the main cause but also a necessary cause of cervical cancer has led to great advances in the prevention of this disease on two fronts: (i) Primary prevention by the use of prophylactic HPV vaccines; and (ii) secondary prevention by increasing the accuracy of cervical cancer screening.     

Frequency and clinical significance of human beta-herpesviruses in cervical samples from Italian women

Human papillomaviruses (HPVs) are necessary, but not sufficient, for the development of cervical cancer (CC). Human beta-herpesviruses (beta-HHVs) have been suggested as possible cofactors in the oncogenesis of CC. In this cross-sectional study, the prevalence and possible association of cytomegalovirus (CMV), HHV-6 and -7 with HPV presence was investigated by quantitative real-time PCR assays in cervical samples obtained from 208 italian women. The two most common high-risk HPV types found were 31 and 16. Overall, the positive rates for CMV, HHV-6 and HHV-7 were 66%, 25%, and 6%, respectively. In particular, the prevalence of CMV was found to be extremely high irrespective of either the cytological category or HPV positivity. The prevalence of HHV-6 DNA was significantly higher in high-grade squamous intraepithelial lesions (HSIL) respect to normal women (P < 0.017); by contrast, the prevalence HHV-7 DNA was generally low and not associated with SIL. Copresence of CMV and HHV-6 DNA was found to be significantly higher in patients with SIL respect to normal women (P < 0.05). No correlation was demonstrated between the viral load of all three beta-HHVs and the different cytological stages or with the HPV presence. A few patients with severe disease however showed very high viral loads which for HHV-6 may be indicative of viral integration. In conclusion, this study suggests that CMV and HHV-7 alone are probably not implicated in the oncogenesis of CC whilst HHV-6 alone or together with CMV may contribute to the development of CC.     

The role of routine outpatient cytological screening for early detection of carcinoma of the cervix in India

Cytological evaluation of cervical smears has been carried out in 4,338 women attending the Gynecology and Obstetrics Department and Family Planning Clinic of Queen Mary's Hospital, Lucknow, India, since April 1971. The incidence of cervical dysplasia was found to be 4.6% (205 out of 4,338) in the series, while malignant smears were detected in 54 patients (1.2%). In five cases, malignant smears were encountered in women with apparently normal cervices, highlighting the advantage of exfoliative cytology in screening subjects without cervical pathology. The remaining 49 cases with malignant smears had lesions on the cervix that had been clinically diagnosed as carcinoma. The diagnosis of malignancy was confirmed by biopsy in all 54 cases showing malignant smears; however, in 10 cases clinically diagnosed as carcinoma of the cervix, and subsequently confirmed histologically, the diagnosis was missed by cytology, the smears being reported as inflammatory in seven and inadequate in three. Cytological evidence of herpes simplex infection was seen in the smears in 23 out of 54 cases of carcinoma, and trichomonal infection was present in 15, indicating some relationship of these infections with the development of neoplastic changes in the cervical epithelium. Eleven of the total 54 cases of carcinoma of the cervix were in the age group of 26-35 yr, and four were in subjects with only two children. This emphasizes the need for the routine cytologic screening of all child-bearing women with parities of two and above, regardless of their age, if any meaningful results are to be obtained in a cancer-screening program in India in view of the prevailing custom of early marriage.     

Atypical glandular cells of undetermined significance (AGUS): cytopathologic features, histopathologic results, and human papillomavirus DNA detection.

We intensively reviewed 137 smears initially classified as atypical glandular cells of undetermined significance (AGUS) to refine cytological criteria for evaluating these cases, evaluate histological outcomes, and assess the value of human papillomavirus (HPV) DNA testing in management. Consenting, nonpregnant study participants were identified from a cohort of 46,009 women receiving routine Pap smear screening in a managed care setting. Colposcopy was performed on all women, and at least one histological sample was obtained from each. Review diagnoses were assigned to smears and biopsy specimens by two separate panels of pathologists. DNA testing for cancer-associated HPV types was performed on rinses of cytological samplers after a smear and thin-layer slide had been made. On review, 47 (34%) smears were reclassified as negative, 44 (32%) as AGUS, 30 (22%) as atypical squamous cells of undetermined significance (ASCUS), and 16 (12%) as squamous intraepithelial lesions (SIL). The 19 smears interpreted as high-grade intraepithelial lesions on review included 13 high-grade SIL (HSIL), two HSIL with AGUS, favor neoplastic (endocervical adenocarcinoma in situ [AIS]), and four AGUS, favor neoplastic (AIS). Review histological diagnoses were negative in 105 (77%), squamous or glandular atypia in four (3%), low-grade SIL (LSIL) in nine (7%), HSIL in 12 (9%), AIS in five (4%, including two with concurrent HSIL), and endometrial carcinoma in one (1%). HPV testing identified 11 (92%) of 12 women with histologically confirmed HSIL and all five with AIS (100%). A high-grade intraepithelial lesion or carcinoma is detected in approximately 14% of women with community-based diagnoses of AGUS who are referred for immediate evaluation. Use of refined cytological criteria and HPV DNA testing may permit improved management of women with AGUS.     

Human papillomavirus DNA in urine samples of women with or without cervical cancer and their male partners compared with simultaneously collected cervical/penile smear or biopsy specimens.

Infection of specific types of high-risk human papillomaviruses (HPVs) causes cervical cancer in women. Conventional test for genital HPV infection requires collection of scraped cervical cells or biopsy specimens, which involves invasive procedures. Utility of non-invasive urine sampling for detection of HPV in women and their male sexual partners is controversial. The validation of this urine-based HPV DNA test is of immense value not only in screening large population and children but also for HPV vaccine monitoring in adolescents. We examined the frequency of high risk HPV types 16 and 18 in simultaneously collected urine samples and cervical scrapes or biopsy specimens from women with cervical cancer and their single lifetime male sexual partners in order to validate the utility of urine sampling as a reliable non-invasive method for detection of genital HPV infection. Thirty women with invasive cervical cancer and their husbands along with 30 age-matched normal healthy women including their husbands were recruited for the study. Cervical biopsies/scrapes from women subjects and penile scrapes from their husbands and urine samples from all of them were collected before taking biopsy or scrapes. HPV-L1 consensus primer as well as high-risk HPV (HPV 16 and 18) type-specific oligo-primers were used for PCR detection of HPV DNA. The total frequency of HPV in women with cervical cancer was found to be 83% (25/30) while it was only 67% (20/30) in their male partners but there was virtually no difference in results between urine and scrape or tissue biopsy either in women or their male partners. Although healthy women and their husbands showed similar frequency of HPV infection both in urine and scrape samples, there was a significant difference (p=0.05) in the prevalence of high risk HPV type 16 in women with cervical cancer (70%) and their male partners (30%). Similar was the trend between control women and their male partners. The results also showed a very high prevalence of HPV type 16 among Indian women with cervical cancer while its frequency was significantly low in their single lifetime male partners. The case by case matching of HPV positivity and negativity between urine and cervical/penile scrapes or biopsies obtained from women and their male partners demonstrated that the non-invasive urine sampling can be reliably used for screening genital HPV infection in both men and women.     

Prevalence and genotype distribution of human papillomavirus in non-neoplastic cervical tissue lesion: cervical erosion

Human papillomavirus (HPV) infection is the commonest sexually transmitted infection, which is associated with various clinical conditions, ranging from asymptomatic infection to malignant disease of the cervix. The aim of this study was to evaluate the prevalence and genotypic distribution of HPV in women with cervical erosion and to compare the results with those in women with a clinically normal cervix. A further aim was to establish the association between HPV infection and cervical cytology results in women with and without cervical erosion. Cervical samples were collected by liquid-based method and consecutively evaluated for the presence of HPV DNA and for cervical cytology. HPV DNA was tested by a nested polymerase chain reaction (PCR) and typed by reverse dot blot genotyping. Cytological classification was made according to Bethesda 2001 criteria. The overall HPV prevalence was 16.9%; HPV DNA was positive in 20.2% of women with cervical erosion and 12.8% in women with normal cervix (P < 0.05). Multiple infections were found in 34.1% of the HPV-positive women. Commonest types were HPV 18 (32.9%), HPV 16 (29.5%), HPV 54 (20.5%), and HPV 6 (17%). Cervical cytology results were abnormal for 5.2% of women with cervical erosion and for 1.3% with clinically normal cervix (P < 0.05). This study detected a high prevalence of HPV infection in women with cervical erosion compared to women with a normal cervix. This data may contribute to the HPV epidemiology in the southeastern Turkey. It is recommended that women with cervical erosion should be given priority in HPV screening programs.     

Gyn?kologische Krebsvorsorge in Deutschland

Cervical cancer screening was introduced in Germany 40?years ago and the incidence of cancer of the cervix has subsequently decreased by close to 70%. The remaining incidence of 5,600?cases per year represents only 2.8% of all newly occurring cases of cancer in women and these cases occur mainly in patients who do not participate in regular screening. Thus, cervical cancer screening by cytological smears has been proven to be successful. The structure of the German cancer screening program is characterized by decentralized organization, exclusive involvement of medical specialists such as gynecologists and pathologists and strict quality assurance. The recruitment is 50% on a yearly basis and the cumulative participation over 3?years reaches 79%. Since 2008 all laboratories are required to report complete data sets to local quality control agencies.The Joint Federal Committee in charge of evaluating new technologies in Germany mandated an inquiry into the possible role of screening by human papillomavirus (HPV) testing. According to this report published by the Institute for Quality Assurance and Efficiency in Healthcare there are indications for advantages. There are, however, no data in the literature as to possible disadvantages of HPV testing. A similar study for the US Preventive Services Task Force was published in May?2011 with almost identical conclusions.     

Cytological physiognomies and genotype distribution of human papillomaviruses among HPV/HIV co-infected and HPV mono-infected women

BackgroundCo-infection of High Risk Human Papillomavirus (HR-HPV) and HIV is thought to favour initiation of intraepithelial squamous cell lesion and subsequent progression to cervical carcinoma.ObjectivesEvaluation of cytological physiognomies in relation to possible age influence and the genotype distribution of human papillomaviruses among HPV/HIV co-infected and HPV monoinfected women in Kisii, Kenya.MethodsThe case-control study enrolled 42 HPV/HIV co-infected and 42 HPV monoinfected women. Cervical swabs were collected in ThinPrep vials for HPV tying and cytological analysis. HPV subtypes were assayed by Xpert® HPV system (GXHPV-CE-10).ResultsMono-infected women aged 30–39 years had the highest proportion of low grade squamous intraepithelial lesion (LSIL) at 14 (16.67%) while the co-infected aged 50–59 years had the highest proportion of high grade squamous intraepithelial lesion (HSIL) at 9 (10.71%). HPV-16 genotype was the most predominant and it increased with age rise. Older coinfected and mono-infected women (>40 years) had HSIL and LSIL as the most predominant cytological grade respectively.ConclusionThe predominance of HPV-16 and HPV-18/45 genotypes in the study setting is a consideration that would benefit targeted prophylactic vaccination programs. HPV testing and cervical cancer screening for young and older women on a regular basis ought to be reinforced.     

The presence of high-risk HPV combined with specific p53 and p16INK4a expression patterns points to high-risk HPV as the main causative agent for adenocarcinoma in situ and adenocarcinoma of the cervix

Adenocarcinoma in situ (ACIS) and adenocarcinoma (AdCA) of the cervix are frequently missed in population-based screening programmes. Adding high-risk HPV (hrHPV) testing to cervical cancer screening might improve the detection rate of ACIS and AdCA. Since the exact proportion of AdCAs of the cervix that can be attributed to hrHPV infection is still a matter of debate, a comprehensive study was performed of hrHPV presence in ACIS and AdCA of the cervix. Archival formalin-fixed specimens of indisputable ACIS (n=65) and AdCA (n=77) of the cervix were tested for hrHPV DNA by GP5+/6+ PCR-enzyme immunoassay (EIA) and type-specific E7 PCR for 14 hrHPV types. Further immunostaining for p16INK4A and p53 was performed to assess alternative pathways of carcinogenesis potentially unrelated to HPV. hrHPV DNA was found in all (100%) ACISs and 72 (94%) cervical AdCAs, whereas none of 20 endometrial AdCAs scored hrHPV-positive. HPV 18 was most prevalent and found as single or multiple infection in 68% of ACISs and 55% of cervical AdCAs. Diffuse immunostaining for p16INK4a, a potential marker of hrHPV E7 function, was significantly more frequent in hrHPV-positive cervical AdCAs (19/20; 95%) than in those without hrHPV (1/5; 20%; p<0.001). Immunostaining for p53, pointing to stabilized wild-type or mutant p53 protein, was significantly more frequent in hrHPV cervical AdCAs negative for hrHPV (p=0.01). No difference in p16INK4a and p53 immunostaining was found between hrHPV-negative cervical AdCAs and endometrial AdCAs. Hence, only a minority of cervical AdCAs displayed absence of HPV DNA and immunostaining profiles suggestive of an aetiology independent of HPV. Since all ACISs and nearly all cervical AdCAs were hrHPV-positive, the incorporation of hrHPV testing in cervical cancer screening programmes is likely to decrease markedly the incidence of cervical AdCA.     

Prevalence,evolution, and features of infection with human papillomavirus: A 15‐year longitudinal study of routine screening of a women population in the north of Spain

Determination of the prevalence of type‐specific human papillomavirus (HPV) is important for the development of new vaccines and to prevent malignancy. The objective of this study was to determine HPV infection in two areas in the north of Spain, and their evolution in the last 15 years. Between 1991 and 2007, 7,930 fresh cervical swabs were obtained from 5,554 women (37.8 ± 11.8 years old). From them, 425 have been followed‐up for an average of 3.7 ± 2.08 years after sampling (range 2–14.6), and 71 for 7.7 ± 2.2 years (range 5–14). Methods based on polymerase chain reaction (PCR) were carried out. Samples from 1,598 (28.8%) women were positive for HPV: 40.9% were under 25 years of age, 34.2% in the 25–35 year age group, 27.2% in the 36–45 year age group, and 19.6% older than 45 years (P < 0.001). HPV was found in 34.4% of the women with cytological alterations versus 23% of women without cervical changes (P < 0.0001). HPV‐16 was present in 25.8% of the women, although the study identified 26 different HPV genotypes. After 3 years of follow‐up, HPV remained or became undetectable in 87% of the cases, and in 5 years 70.3%. The prevalence of HPV is associated with younger women and women with cytological changes in the cervix. Although HPV‐16 is more prevalent, HPV types not included in available vaccines were found the most commonly. The low 3‐year (even 5‐year) cumulative incidence rate of HPV infection suggests that cervical screening every 3 (or even 5) years is safe and effective. J. Med. Virol. 82:597–604, 2010. © 2010 Wiley‐Liss, Inc.