DNA sequences of human papillomavirus types 11, 16, and 18 in lesions of the uterine cervix in the west of Scotland.

Punch biopsy specimens of the cervix were examined both histologically and for the presence of human papillomavirus (HPV) DNA sequences. The presence of HPV DNA sequences was sought with the Southern blot technique using radioactively labelled HPV-6, 11, 16, and 18 DNA probes, both together and separately. Twenty six biopsy specimens were examined. Histological examination showed cervical intraepithelial neoplasia grade 2 or 3 in 16 specimens, viral changes (koilocytosis) in four, and inflammation or a normal appearance in three. Eleven specimens were negative for HPV DNA sequences, 10 contained HPV-16 DNA, four contained HPV-18 DNA, and one contained both HPV-18 and HPV-11 DNA. Episomal HPV-16 DNA was detected in one case of cervical intraepithelial neoplasia grade 3 and in five cases of cervical intraepithelial neoplasia grade 2/3 with koilocytosis; and episomal HPV-18 DNA was found in two specimens classed as cervical intraepithelial neoplasia grade 2/3, one of which also contained HPV-11 DNA, and in one specimen that showed viral changes alone. Integrated HPV DNA was found in six specimens (four with HPV-16 DNA and two with HPV-18 DNA), including two cases of chronically inflamed cervix with no histological evidence of viral infection or cervical intraepithelial neoplasia. Detection of viral DNA in early lesions may identify patients at risk of malignant progression. This is the first report of HPV-18 DNA in cervical intraepithelial neoplasia in Scotland.     

Human papillomavirus infection and cervical intraepithelial neoplasia in women with renal allografts.

An increased prevalence of cervical cancer has been observed in immunosuppressed women, but controlled studies are rare. Biopsy specimens from 49 women with renal allografts and 69 non-immunosuppressed controls (with no history of cervical intraepithelial neoplasia, vulval warts, or abnormal results of cervical smear tests) were assessed for colposcopic appearance, cytological and histological diagnosis, and the presence of human papillomavirus types 6/11 and 16/18 DNA sequences. At colposcopy 26 (53%) of the women with allografts had cervical abnormalities compared with 20 (29%) of the controls. The prevalence of cervical intraepithelial neoplasia was significantly higher in the women with allografts (24 (49%) compared with 7 (10%]. The overall rate of detection of human papillomavirus DNA did not differ significantly between the two groups. There was however, a significant difference in the rate of detection of human papillomavirus type 16/18 DNA (27% in the women with allografts and 6% in the controls). These data confirm that pathological and virological changes affecting the cervix are significantly increased in immunosuppressed women and emphasise the need for regular colposcopic examination.     

Human papillomavirus infection of the uterine cervix of women without cytological signs of neoplasia.

One hundred and six patients were studied whose cervical smears showed only non-specific inflammatory changes. Screening for genital pathogens yielded only a few positive cases. Histological examination of biopsy specimens taken by colposcopically directed tissue sampling showed cervical intraepithelial neoplasia in 13 of the women (12.3%). Deoxyribonucleic acid (DNA) hybridisation techniques were used to detect human papillomavirus, which was found in 24 patients (22.6%). In a second group of 104 patients with normal cervical cytology tissue biopsy samples were obtained and examined histologically but in no case was cervical intraepithelial neoplasia found. On DNA hybridisation, however, 12 patients (11.5%) were found to be positive for human papillomavirus. In this group finding human papillomavirus DNA was usually associated with a columnar ectopy. An association between human papillomavirus type 16 DNA and both cervical intraepithelial neoplasia and cervical cancer is well established. In this study it was type 16 which occurred most frequently in both groups.     

Prevalence of human papillomavirus genotypes in cervical cancer and precursor lesions

There are no data obtained in biopsy material on the prevalence of human papillomavirus (HPV) and HPV genotypes in Croatian women with cervical carcinoma and precursor lesions. Therefore, the prevalence of HPVand HPVgenotypes was investigated in archival material of cervical carcinoma and precursor lesions kept at Department of Pathology, School of Medicine, University of Rijeka. DNA was isolated from formalin fixed, paraffin embedded tissue, histologically classified as cervical intraepithelial neoplasia (CIN) III (n =43), squamous cell carcinoma (SCC) (n =54) and adenocarcinoma (ADC) (n =40). HPV testing was performed bypolimerase chain reaction (PCR) using generic and genotype specific primers. The prevalence of HPV DNA was 93.02%, 92.59%, and 92.5% in CIN III, SCC and ADC, respectively. In CIN III and SCC, HPV-16 was the most common high-risk genotype, identified in 65% and 52%, followed by HPV-18 in 22.5% and 28% of cases, respectively. HPV-18 showed a statistically significant prevalence in ADC (67.6%) as compared with SCC (chi(2)=9.924; p_ 0.01). Study results revealed a high prevalence of HPV-DNA in examined cervical lesions (>90%). HPV-16 predominated in SCC and HPV-18 in ADC. Single infection was more frequently present than multiple infections in all three histological groups.     

Comparison of the detection of cervical human papillomavirus infection by filter DNA hybridization of cytologic specimens and by in situ DNA hybridization of tissues

Cellular samples and subsequent cone biopsy samples from the same site in 18 patients were screened for infection with human papillomavirus (HPV) types 16 and 18 (HPV 16/18) by DNA hybridization. Filter hybridization of cells collected using cervical swabs was significantly less sensitive (with only 4 positive results) in detecting HPV 16/18 DNA sequences than was in situ hybridization of tissue sections (with 16 positive results). The in situ hybridization results correlated well with the cytologic and histologic findings of cervical intraepithelial neoplasia of grades II (mild dysplasia) and III (severe dysplasia and carcinoma in situ).     

Isolation of a novel human papillomavirus (type 51) from a cervical condyloma.

We cloned the DNA from a novel human papillomavirus (HPV) present in a cervical condyloma. When DNA from this isolate was hybridized at high stringency with HPV types 1 through 50 (HPV-1 through HPV-50), it showed weak homology with HPV-6 and -16 and stronger homology with HPV-26. A detailed restriction endonuclease map was prepared which showed marked differences from the maps for other HPVs that have been isolated from the female genital tract. Reassociation kinetic analysis revealed that HPV-26 and this new isolate were less than 10% homologous; hence, the new isolate is a novel strain of HPV. The approximate positions of the open reading frames of the new strain were surmised by hybridization with probes derived from individual open reading frames of HPV-16. In an analysis of 175 genital biopsies from patients with abnormal Papanicolaou smears, sequences hybridizing under highly stringent conditions to probes from this novel HPV type were found in 4.2, 6.1, and 2.4% of biopsies containing normal squamous epithelium, condylomata, and intraepithelial neoplasia, respectively. In addition, sequences homologous to probes from this novel isolate were detected in one of five cervical carcinomas examined.     

Detection of human papillomavirus DNA in skin warts from immunocompromised patients but not in semen from men whose wives have abnormal cervical cytology.

The epidemiology of human papillomaviruses (HPV) was studied in 61 immunocompromised patients (e.g. renal and cardiac transplants; Bowen's disease; genital cancer) undergoing therapy at the University Hospital of Wales at Cardiff U.K. Warts from various sites of these patients were studied for the presence of HPV types 6, 11, 16 and 18 using the dot-blot DNA hybridization technique. Four HPV-16 and one HPV-11 was detected. The presence of HPV-16 in our study is quite significant since it suggests the potential occurrence of genital HPV types in skin warts in immunocompromised patients and hence the need for screening such patients against HPV types. HPV, mainly types 16 and 18 are usually associated with genital cancer, cervical malignancies and cervical intraepithelial neoplasia. The semen of the husband of 30 women with cervical abnormalities and the semen of 30 husbands (control) of wives with normal cervix were tested for HPV-6, 11, 16 and 18. No HPV-DNA could be detected in all of the 60 specimen. This suggests that specimens were either truly negative for any of those types or because virus DNA could present in a small amount less than 5 pg/microliters in some patients. Whether semen plays a role in transmitting HPV is still controversial.     

Analysis of the physical state of different human papillomavirus DNAs in intraepithelial and invasive cervical neoplasm.

The integration of human papillomavirus (HPV) DNA into the human genome has been generally accepted as a characteristic of malignant lesions. To gain a better understanding of this phenomenon, genomic DNA from 181 cervical biopsy specimens was isolated and analyzed for HPV type and physical state of the HPV genome. These specimens represented the full spectrum of cervical disease, from condyloma to invasive carcinoma. Discrimination between integrated and episomal HPV DNA was accomplished by the detection of HPV-human DNA junction fragments on Southern blots. In most cases in which ambiguous Southern blot results were obtained, the specimens were reanalyzed by two-dimensional gel electrophoresis. Of the 100 biopsy specimens of cervical intraepithelial neoplasia analyzed, only 3 showed integrated HPV DNA, in contrast to 56 (81%) of 69 cervical carcinomas (P less than 0.001) showing integrated HPV DNA. Of the 40 carcinomas containing HPV 16 DNA, 29 (72%) had integrated HPV DNA, of which 8 (20%) also had episomal HPV DNA. In 11 (27%) cancers, only episomal HPV 16 DNA was detected. All 23 HPV 18-containing carcinomas had integrated HPV DNA, and 1 also had episomal HPV 18 DNA. The difference between HPV types 16 and 18 with respect to frequency of integration was statistically significant (P less than 0.01). The results of this study indicate that detectable integration of HPV DNA, regardless of type, occurs infrequently in cervical intraepithelial neoplasia. The absence of HPV 16 DNA integration in some carcinomas implies that integration is not always required for malignant progression. In contrast, the consistent integration of HPV 18 DNA in all cervical cancers examined may be related to its greater transforming efficiency in vitro and its reported clinical association with more aggressive cervical cancers.     

The Cytological Prediction of Cervical Intraepithelial Neoplasia In Colposcopically Directed Biopsies

The tissue sections and preceding cervical smears of 1262 women who had colposcopic cervical biopsies were reviewed and the reports correlated. Close correlation between the cytological and histological findings, to within one histological grade of cervical intraepithelial neoplasia (CIN), was noted in 86% of cases. However, the biopsy was negative, or contained evidence of wart virus infection only, in 24% of cases where dyskaryotic cells had been observed in the cervical smear. Of particular concern was the fact that negative histological findings were recorded in 13% of cases where the smear contained cells showing a moderate dyskaryosis and in 1.26% of cases where the smear showed severe dyskaryosis. This suggests that colposcopically directed biopsies do not always reflect the underlying pathological changes in the cervix. Management of these cases is discussed. In 45 women with a normal cervical smear prior to biopsy, histology revealed seven cases of CIN 3 and one case of invasive squamous carcinoma. This indicates that referral for colposcopy is advisable whenever there is clinical suspicion of cancer, even if the cervical smear report is normal.     

Genital human papillomavirus testing by in situ hybridization in liquid atypical cytologic materials and follow-up biopsies

OBJECTIVE: To describe cases of HPV testing by DNA in situ hybridization performed on atypical cervicovaginal samples collected by a liquidsed method that were negative for HPV DNA on cytology but revealed cervical intraepithelial neoplasia on follow-up biopsies. STUDY DESIGN: Three hundred ninety-five consecutive SurePath atypical squamous cells of undetermined significance (ASC-US) cytologic samples from asymptomatic, reproductive-age women were tested for human papillomaviruses (HPVs) by the in situ hybridization (ISH) method (Ventana Inform HPV Test, Tucson, Arizona, U.S.A). One hundred (25%) cases underwent follow-up colposcopic biopsy within 3 months of cytology. All the tests (cytology, ISH, histology) were independently evaluated without knowledge of the other tests. RESULTS: One hundred twenty-two (33%) cytologic samples were positive for HPVs. Of a total of 100 (HPV positive and negative) follow-up biopsies, 55 were positive for cervical intraepithelial neoplasia (CIN). Fourteen cases of biopsy-proven CIN tested negative for all HPV types in the prior cytologic samples. Retesting of the 14 CIN tissues by ISH was negative in 10, positive for HPV in 2 and inconclusive in 2. CONCLUSION: There is a small but significant (14%) false negative rate with HPV testing by the Ventana ISH method. Clinically suspicious cases should be followed even if an HPV test is negative.     

Opportunities to improve the prevention and treatment of cervical cancer

Human papillomavirus (HPV) is a causal agent for approximately 5.3% of cancers worldwide, including cervical cancer, and subsets of genital and head and neck cancer. Persistent HPV infection is a necessary, but not sufficient, cause of cervical cancer. Of the >100 HPV genotypes, only about a dozen, termed "high-risk", are associated with cancer. HPV-16 is present in approximately 50% of all cervical cancers and HPV-16, HPV-18, HPV-31 and HPV-45 together account for approximately 80%. Most high-risk HPV infections are subclinical, and are cleared by the host's immune system. The remainder produces low or high-grade squamous intraepithelial lesions (SILs), also called cervical intraepithelial neoplasia (CIN), which also may regress spontaneously. However persistent high grade SIL represents the precursor lesion of cervical cancer and carcinogenic progression is associated with integration of the viral DNA, loss of E2 and upregulation of viral oncogene expression, and chromosomal rearrangements like 3q gain. Cytologic screening of the cervix for SIL and intervention has reduced the incidence of cervical cancer in the US by an estimated 80% and HPV viral DNA and other molecular tests may improve screening further. The licensure of a preventive HPV vaccine ushers in a new era, but issues remain, including: protection restricted to a few oncogenic HPV types, access in low resource settings and impact on current cytologic screening protocols. Importantly, preventive HPV vaccination does not help with current HPV infection or disease. Here we examine the potential of second-generation preventive HPV vaccines and therapeutic HPV vaccination to address these outstanding issues.     

Quantitative DNA analysis of low grade cervical intraepithelial neoplasia and human papillomavirus infection by static and flow cytometry.

Quantitative deoxyribonucleic acid (DNA) analysis of cervical biopsy specimens from 26 women with cytological, colposcopic, and histological evidence of mild cervical atypia consistent with cervical intraepithelial neoplasia grade I, reactive atypia, or human papillomavirus infection alone or in combination was performed in a comparative evaluation of Feulgen microspectrophotometry, the fast interval processor image analysis system, and flow cytometry. The fast interval processor image analysis system showed a distinct advantage over the other methods, being faster and allowing the operator to see the cells that were selected for measurement. The three methods of measurement together showed that the DNA content of at least 2% of the cells measured exceeded 5C (C being the haploid amount of DNA in a normal cell and 2C representing the diploid complement of a normal cell) in all cases of cervical intraepithelial neoplasia grade I and reactive atypia and in 87% of those reported as showing human papillomavirus infection alone. In contrast, the DNA content of cervical biopsy specimens from the transformation zone of 11 normal controls did not exceed 4C. This study shows the value of using a DNA threshold--that is, the "5C exceeding rate"--to distinguish between normal and neoplastic appearances of the cervix. These results support the view that cervical infection by human papillomavirus is a true precursor of neoplasia.     

PCR diagnosis of HPV in cervical biopsies of CIN and invasive neoplasia formerly diagnosed as HPV negative

OBJECTIVE: To evaluate whether the polymerase chain reaction (PCR) enhances the diagnosis of human papillomavirus (HPV) in biopsies of the uterine cervix with cervical intraepithelial neoplasia (CIN) or invasive neoplasia. STUDY DESIGN: Samples of 71 paraffin-embedded cervical tissue blocks from patients seen in the period 1997-1998 were analyzed. Samples were selected according to age (18-60 years old) and an active sexual life and divided in to 3 groups: test (samples with CIN or invasive neoplasia and a negative HPV diagnosis), positive controls (samples with CIN or invasive neoplasia and a positive HPV diagnosis) and negative controls (samples without CIN or invasive neoplasia and a negative HPV diagnosis). Samples were subjected to DNA extraction and PCR for HPV detection. RESULTS: PCR analysis matched the colposcopic and cytopathologic diagnoses in the positive and negative controls. However, 77% of samples in test group were HPV positive. CONCLUSION: CIN, an invasive neoplasm, is associated with the presence of HPV. Colposcopy and cytopathology are efficient but not sufficient to identify HPV. Thus, despite the high cost, PCR can be used as an additional examination, in women with cervical lesions.     

Southern blot and dot blot hybridisation compared to PCR for the detection of human papillomavirus DNA in biopsies of the uterine cervix from women with dysplasia

The aim of this study was to compare the sensitivity of Southern blot (SB) and dot blot (DB) hybridisation with polymerase chain reaction (PCR) for the detection of HPV in cervical biopsies from samples with differing histology. One hundred and forty seven women with cervical dysplasia had biopsies performed; one sample was analyzed for HPV DNA from types 6/11, 16, and 18 by SB, DB and PCR (L1 consensus primer and type specific probes) while an adjacent sample was examined histologically. The histology of the samples was normal in 40 (27%), squamous metaplasia in 25 (17%), inflammation 2 (1%) HPV infection 24 (17%), cervical intraepithelial neoplasia (CIN) grade I in 11 (7%), CIN II in 18 (12%), CIN III in 22 (15%), while 5 (3%) had invasive cancer. The number of biopsies positive for HPV DNA from types 6/11, 16, and 18, using the different hybridisation methods was 56 (38%) by dot blot, 57 (39%) by Southern blot hybridisation and 66 (45%) by PCR. When the L1 consensus primer was used 100 (68%) specimens were positive by PCR. The sensitivity of SB and DB hybridisation, as compared with PCR (type specific probes 6/11, 16, 18) was greater in biopsies with abnormal histology (histological grades of HPV infection and greater, as a group) (sensitivity of SB 83%, DB 74%) than those with normal and metaplastic change (as a group) (sensitivity of SB 44%, DB 35%) (P < 0.005 for SB and DB) (inflammation excluded from analysis). This study demonstrated that the sensitivity of SB and DB hybridisation, relative to PCR is greater in samples with abnormal histology than in samples with normal histology.     

HLA DOA1 and DOB1 loci in Honduran women with cervical dysplasia and invasive cervical carcinoma and their relationship to human papillomavirus infection.

Molecular and epidemiological studies have demonstrated that certain types of human papillomavirus (HPV), mainly HPV-16 and HPV-18, are the primary causes of cervical cancer and its precursor lesions; there is now evidence for a clear association with specific HLA class I and class II loci contributing independently to the expression of cervical cancer. Among Honduran women carcinoma of the cervix is the most common type of cancer, and infections with high-risk HPV types are highly prevalent. To study the interactive role of viral-host genetics, we performed PCR amplification of DNA and sequence-specific oligonucleotide probe typing on cervical scrapes from 49 women [24 with cervical intraepithelial neoplasia stage III or cervical cancer (severe cases) and 25 with stage I or II cervical intraepithelial neoplasia (mild cases)] and 75 control subjects to look for possible associations between HPV and HLA class II DQA1 and DQB1 alleles in the development of dysplasias and invasive cancer. This analysis revealed a predominance of HLA-DQA1*0301 among severe-case patients [relative risk (RR) = 3.45, p = 0.008), whereas DQA1*0501 was negatively associated (RR = 0.30, p = 0.03), suggesting a protective effect of this allele. HPV typing showed a decreased relative risk among the HPV-16 or HPV-18 carrying patients and other HPV-related positive patients in the presence of DQB1*0602 compared with positive control subjects (p = 0.04). No statistically significant allele frequency difference was observed between mild dysplasia cases and control subjects. The results suggest that DQA1*03011, which is in linkage desequilibrium with all HLA-DR4 alleles, confers an increased risk for severe cervical dysplasia and invasive cancer, whereas DQA1*0501, which is in several DR52 haplotypes, has a protective effect. Furthermore, specific HLA-DQB1 sequences may be important in determining the immune response to HPV peptides and may affect the risk for cervical cancer after HPV infection in mestizo Honduran women.     

Original cervical cytology and follow-up biopsy results in positive high risk human papillomavirus DNA tests with high-level resuls

OBJECTIVE: To ascertain Pap test and biopsy results of specimens with high level of human papillomavirus (HPv) DNA and compare atypical squamous cells of undetermined signiqicance (ASC-US) populations with HPV DNA. STUDY DESIGN: Positive HPV tests with relative light unit (RLU) values > or =1000 were identified and original Pap test and follow-up biopsy results recorded. Pap test and biopsy results for ASC-US were compared to positive results with RLU <1000. RESULTS: From 1892 total HPV-positive tests, 156 specimens with high RLU were identified; 145 had biopsies. The interpretations of the corresponding Pap tests were as follows: negative for intraepithelial lesion and malignancy, 3; ASC-US, 87; ASC, cannot exclude high grade squamous intraepithelial lesion, 5; low grade squamous intraepithelial lesion, 40 and high grade squamous intraepithelial lesion, 10. Biopsies showed 60 negative, 58 cervical intraepithelial neoplasia (CIN) 1 and 27 CIN 2+. In the highly positive ASCUS group, biopsy showed higher percentage of CIN 1 (33% vs. 16%) compared to the low-positive group. CONCLUSION: Compared to low-positive results, high-positive results showed more abnormal Pap tests. CIN 1 was a more likely result for high-positive ASCUS. More transient infections may account for these findings. The results do not argue for different management schemes between the categories.     

Identification of the HPV-16 E6 protein from transformed mouse cells and human cervical carcinoma cell lines.

Human cervical carcinoma cell lines that harbor human papillomavirus (HPV) have been reported to retain selectively and express HPV sequences which could encode viral E6 and E7 proteins. The potential importance of HPV E6 to tumors is suggested further by the observation that bovine papillomavirus (BPV) E6 can induce morphologic transformation of mouse cells in vitro. To identify HPV E6 protein, a polypeptide encoded by HPV-16 E6 was produced in a bacterial expression vector and used to raise antisera. The antisera specifically immunoprecipitated the predicted 18-kd protein in two human carcinoma cell lines known to express HPV-16 RNA and in mouse cells morphologically transformed by HPV-16 DNA. The 18-kd E6 protein was distinct from a previously identified HPV-16 E7 protein. The HPV-16 E6 antibodies were found to be type specific in that they did not recognize E6 protein in cells containing HPV-18 sequences and reacted weakly, if at all, to BPV E6 protein. The results demonstrate that human tumors containing HPV-16 DNA can express an E6 protein product. They are consistent with the hypothesis that E6 may contribute to the transformed phenotype in human cervical cancers that express this protein.     

Prevalence of human papillomavirus types in women with pre-neoplastic and neoplastic cervical lesions in the Federal District of Brazil

As a contribution to the public health authorities in planning prophylactic and therapeutic vaccine strategies, we describe the prevalence of human papillomavirus (HPV) types in women presenting abnormal cytological results in Pap smear screening tests in the Federal District, Central Brazil. We studied 129 cervical scraping samples from women whose cytological tests showed either pre-neoplastic or neoplastic lesions. Amplification of HPV DNA was performed by polymerase chain reaction using consensus primers MY09 and MY11 followed by identification of isolates by restriction fragment length polymorphism. We detected HPV DNA in 62% of the samples, including HPV-16 in 43.8%, HPV-58 in 12.5%, HPV-31 in 10%, HPV-53 in 6.3%, each of HPV-18 and HPV-33 in 3.8% of the isolates. Other types (HPV-35, -52, -66, -CP8304, -6, -11, and -CP8061) were less frequent (= or < 2.5% each). The prevalence of HPV-58 was relatively higher in this population than in data in South America, but similar to results obtained in other studies in Latin America, Europe, and Eastern Asia. Case-control studies need to be carried out to establish the association between the prevalence of HPV types specially the less frequent high-risk types and cervical cancer.     

Significance of HPV-58 Infection in Women Who Are HPV-Positive,Cytology-Negative and Living in a Country with a High Prevalence of HPV-58 Infection

Purpose

Cervical cytology and human papillomavirus (HPV) DNA co-testing is recommended as a screening method for detecting cervical lesions. However, for women who are HPV-positive but cytology-negative, the appropriate management and significance of HPV-58 infection remain unknown.

Methods

This study of prevalent HPV detected at baseline with a median follow-up of 3.2 years evaluated the risk factors associated with cervical abnormalities and assessed the significance of HPV-58 infection. A total of 265 women were enrolled. All high-grade squamous intraepithelial lesions (HSIL) that were detected by cytology were confirmed by histology. Histological diagnoses of cervical intraepithelial neoplasia 2/3 were classified as HSIL. Women were classified into four groups according to the HPV genotype that was detected at their first visit: HPV-58 (n = 27), HPV-16 (n = 52; 3 women had HPV-58 co-infection), ten other high risk (HR) types (n = 79), or low/undetermined risk types (n = 107).

Results

Of 265 women, 20 (7.5%) had HSIL on their follow-up examinations. There were significant differences in the cumulative incidence of HSIL between the four groups (p<0.001). The 5-year cumulative incidence rates of HSIL were 34.0% (95% CI: 17.3–59.8%) in HPV-58 positive cases, 28.0% (95% CI: 13.8–51.6) in HPV-16 positive cases, 5.5% (95% CI: 2.1–14.0%) in one of the ten other types of HR-HPV positive cases, and 0% in women with low/undetermined risk HPV. When seen in women with HR-HPV (n = 158), persistent HPV infection was a significant factor associated with the development of HSIL (hazard ratio = 15.459, 95% CI: 2.042–117.045). Women with HPV-58 had a higher risk (hazard ratio = 5.260, 95% CI: 1.538–17.987) for the development of HSIL than women with HPV-16 (hazard ratio = 3.822, 95% CI: 1.176–12.424) in comparison with women with other types of HR-HPV.

Conclusion

HPV-58 has a high association with the development of HSIL in women who are HPV-positive and cytology-negative.