Disease detection at the 48-month exit round of the HPV FOCAL cervical cancer screening trial in women per-protocol eligible for routine screening

HPV FOCAL is a randomized control trial of cervical cancer screening. The intervention arm received baseline screening for high-risk human papillomavirus (HPV) and the control arm received liquid-based cytology (LBC) at baseline and 24 months. Both arms received 48-month exit HPV and LBC cotesting. Exit results are presented for per-protocol eligible (PPE) screened women. Participants were PPE at exit if they had completed all screening and recommended follow-up and had not been diagnosed with cervical intraepithelial neoplasia Grade 2 or worse (CIN2+) earlier in the trial. Subgroups were identified based upon results at earlier trial screening. There were 9,457 and 9,552 and women aged 25–65 randomized to control and intervention and 7,448 (77.8%) and 8,281 (86.7%), respectively, were PPE and screened. Exit cotest results were similar (p = 0.11) by arm for PPE and the relative rate (RR) of CIN2+ for intervention vs. control was RR = 0.83 (95% CI: 0.56–1.23). The RR for CIN2+ comparing intervention women baseline HPV negative to control women with negative cytology at baseline and at 24 months, was 0.68 (95% CI: 0.43–1.06). PPE women who had a negative or CIN1 colposcopy in earlier rounds had elevated rates (per 1,000) of CIN2+ at exit, control 31 (95% CI: 14–65) and intervention 43 (95% CI: 25–73). Among PPE women HPV negative at exit LBC cotesting identified little CIN2+, Rate = 0.3 (95% CI: 0.1–0.7). This per-protocol analysis found that screening with HPV using a 4-year interval is as safe as LBC with a 2-year screening interval. LBC screening in HPV negative women at exit identified few additional lesions.     

Effectiveness of novel,lower cost molecular human papillomavirus‐based tests for cervical cancer screening in rural china

This study examined the efficacy of the OncoE6? Cervical Test, careHPV? and visual inspection with acetic acid (VIA) in identifying women at risk for cervical cancer and their capability to detect incident cervical precancer and cancer at 1‐year follow‐up. In a population of 7,543 women living in rural China, women provided a self‐collected and two clinician‐collected specimens and underwent VIA. All screen positive women for any of the tests, a ～10% random sample of test‐negative women that underwent colposcopy at baseline, and an additional ～10% random sample of test‐negative women who did not undergo colposcopy at baseline (n = 3,290) were recruited. 2,904 women were rescreened 1 year later using the same tests, colposcopic referral criteria, and procedures. Sensitivities of baseline tests to detect 1‐year cumulative cervical intraepithelial neoplasia Grade 3 or cancer (CIN3+) were 96.5% and 81.6% for careHPV? on clinician‐collected and self‐collected specimens, respectively, and 54.4% for OncoE6? test. The OncoE6? test was very specific (99.1%) and had the greatest positive predictive value (PPV; 47.7%) for CIN3+. Baseline and 1‐year follow‐up cervical specimens testing HPV DNA positive was sensitive (88.0%) but poorly predictive (5.5–6.0%) of incident CIN2+, whereas testing repeat HPV16, 18 and 45 E6 positive identified only 24.0% of incident CIN2+ but had a predictive value of 33.3%. This study highlights the different utility of HPV DNA and E6 tests, the former as a screening and the latter as a diagnostic test, for detection of cervical precancer and cancer.     

Health impact of delayed implementation of cervical cancer screening programs in India: A modeling analysis

India has the highest burden of cervical cancer in the world. To estimate the consequences of delaying implementation of organized cervical cancer screening, we projected the avertable burden of disease under different implementation scenarios of a screening program. We used an individual-based microsimulation model of human papillomavirus (HPV) infection and cervical cancer calibrated to epidemiologic data from India to project age-specific cancer incidence and mortality reductions associated with screening (once-in-a-lifetime among women aged 30–34 years) with one-visit visual inspection with acetic acid (VIA) and one- and two-visit HPV DNA testing. We then applied these reductions to a population model to project the lifetime cervical cancer cases and deaths averted under different implementation scenarios taking place from 2017 to 2026: (1) immediate implementation of screening with currently available screening tests (one-visit VIA, two-visit HPV testing); (2) immediate implementation of screening with currently available screening tests, with a switch to point-of-care one-visit HPV testing in 5 years; and (3) 5-year delayed implementation of screening with current screening tests or point-of-care HPV testing. Immediate implementation of two-visit HPV testing with a switch to one-visit HPV testing averted 574,100 cases and 382,500 deaths over the lifetimes of 81.4 million 30- to 34-year-old women screened once between 2017 and 2026. Delayed implementation with a one-visit HPV test averted 209,300 cases and 139,100 deaths. Delaying implementation of screening programs in high-burden settings will result in substantial morbidity and mortality among women beyond the age for adolescent HPV vaccination.     

High‐grade cervical abnormalities and cervical cancer in women following a negative Pap smear with and without an endocervical component: A cohort study with 10 years of follow‐up

The proportion of Pap smears containing an endocervical component (ECC) has been declining in Australia. Given that ECC negative (ECC?) smears may be associated with reduced sensitivity, we undertook a retrospective cohort study to estimate rates of histologically confirmed high‐grade cervical abnormality (HGA) and cancer in women with negative Pap smears with and without an ECC. Women 18‐69 years with at least two Pap smears between 1 January 2001 and 31 December 2010 with the first smear in that period (index smear) showing no abnormality were eligible. Follow‐up ended at date of the first abnormal smear, date of histological diagnosis, date of hysterectomy, date of death, or 31 December 2010, whichever came first. ECC status was treated as a time varying exposure. Follow‐up was split at each smear after the index smear. Poisson regression was used to estimate adjusted incidence rates and incidence rate ratios (IRR) by ECC status. The incidence rate of histologically confirmed HGA was significantly lower following ECC? smears than after ECC+ smears (adjusted IRR: 0.69, 95%Confidence Interval (CI) 0.62‐0.77), particularly at older ages (interaction between ECC status and age, p = 0.001). In contrast, the overall rate of invasive cancer was not significantly different after ECC? than after ECC+ smears (IRR: 1.27, 95%CI 0.90‐1.77). In conclusion, women had a lower rate of confirmed HGA and no significant increase in the rate of invasive cervical cancer following ECC? smears. This study does not support differential (accelerated) follow‐up in women with a negative smear without an endocervical component.     

Visual inspection as a cervical cancer screening method in a primary health care setting in Africa

We evaluated the feasibility and performance of visual inspection with acetic acid (VIA) and Lugol's iodine (VILI) for cervical cancer screening in a primary health-care setting in Kinshasa, Congo. Women (1,528) aged > or =30 years were screened independently by nurses and physicians by VIA and VILI and Pap cytology. Biopsy samples were obtained from women with abnormal colposcopies and from 290 randomly chosen women with normal colposcopy. Cytological and histological examinations were performed in Lyon and Montreal, respectively. The prevalence of cervical intraepithelial neoplasia (CIN) of grades 1, 2 and 3 was 4.5, 1.3 and 4%, respectively. Using biopsy as the reference, the sensitivity, specificity and negative predictive value (NPV) for > or =CIN 2 for VIA-nurse were 55.5% (95% CI: 34.7-76.2), 64.6% (95% CI: 62.0-67.1) and 96.8% (95% CI: 93.5-98.7), respectively. The corresponding values for VILI-nurse were 44.0% (95% CI: 24.2-63.8), 74.6% (95% CI: 72.3-76.9) and 96.7% (95% CI: 93.7-98.6). The equivalent parameters for physicians were 71.1% (95% CI: 46.7-95.5), 71.3% (95% CI: 68.9-73.6) and 98.6% (95% CI: 96.0-99.7) for VIA and 68.3% (95% CI: 42.5-94.0), 76.2% (95% CI: 74.0-78.4) and 97.2% (95% CI: 95.3-98.5) for VILI. The sensitivity of cytology ranged between 31 and 72%, depending on the abnormality threshold used to define positivity, with a corresponding specificity range of 94-99% and a NPV range of 97-99%. Our results show that VIA and VILI performed by nurses and physicians are slightly more sensitive but less specific than Pap cytology across multiple combinations of test and lesion thresholds. Given their lower cost and easy deployment, visual inspection methods merit further assessment as cervical cancer screening methods for low-resource countries.     

Management of HPV-positive women in cervical screening using results from two consecutive screening rounds

We studied whether triage of human papillomavirus (HPV)-positive women participating in an HPV-based screening programme can be improved by including the HPV result at the previous screen in the triage algorithm. We analyzed data of a subgroup of 366 women from the POBASCAM trial, screened by cytology and HPV cotesting. Women were included if they tested HPV-positive in the second HPV-based screening round. We evaluated the clinical performance of 16 strategies, consisting of cytology, HPV genotyping, and/or previous screen HPV result. The clinical endpoint was cervical precancer or cancer (CIN3+). The current Dutch triage testing policy for HPV-positive women is to refer women for colposcopy if they have abnormal cytology at baseline or after 6–18 months. In the second HPV-based screening round, this strategy yielded a negative predictive value (NPV) of 95.8% (95% confidence interval: 91.9–98.2) and colposcopy referral rate of 37.6% (32.3–43.2%). Replacing repeat cytology by the previous screen HPV result yielded a similar NPV (96.9%, 93.3–98.9) and colposcopy referral rate (38.8%, 33.4–44.4). A higher NPV (99.2%, 96.3–100%) at the cost of a higher colposcopy referral rate (49.2%, 43.6–54.8) was achieved when cytology was combined with HPV16/18 genotyping. The other 13 triage strategies yielded a lower NPV, a higher colposcopy referral rate or performed similarly but required additional testing. HPV-positive women in the second HPV-based screening round can be suitably managed by cytology, HPV16/18 genotyping and the HPV result at the previous screen, obviating the need for repeat testing of HPV-positive, cytology negative women.     

Increasing participation in cervical cancer screening: Offering a HPV self‐test to long‐term non‐attendees as part of RACOMIP,a Swedish randomized controlled trial

RACOMIP is a population‐based, randomized trial of the effectiveness and cost‐effectiveness of different interventions aimed at increasing participation in a well‐run cervical cancer screening program in western Sweden. In this article, we report results from one intervention, offering non‐attendees a high‐risk human papillomavirus (HPV) self‐test. Comparison was made with standard screening invitation routine or standard routine plus a telephone call. Women (8,800), aged 30–62, were randomly selected among women without a registered Pap smear in the two latest screening rounds. These women were randomized 1:5:5 to one of three arms: 800 were offered a high‐risk HPV self‐test, 4,000 were randomized to a telephone call (reported previously) and 4,000 constituted a control group (standard screening invitation routine). Results were based on intention to treat analysis and cost‐effectiveness was calculated as marginal cost per cancer case prevented. The endpoint was the frequency of testing. The total response rate in the self‐testing arm was 24.5%, significantly higher than in the telephone arm (18%, RR 1.36, 95% CI 1.19–1.57) and the control group (10.6%, RR 2.33, 95% CI 2.00–2.71). All nine women who tested positive for high‐risk HPV attended for a cervical smear and colposcopy. From the health‐care sector perspective, the intervention will most likely lead to no additional cost. Offering a self‐test for HPV as an alternative to Pap smears increases participation among long‐term non‐attendees. Offering various screening options can be a successful method for increasing participation in this group.     

Initial results from a randomized trial of cervical visual screening in rural south India

The impact of a single round of screening of visual inspection with acetic acid (VIA) on cervical cancer incidence and mortality was investigated in a cluster randomized trial in south India. Women 30-59 years of age in 113 clusters in Dindigul District were randomized to VIA screening (57 clusters, 48,225 women) by nurses and to a control group (56 clusters, 30,167 women). 30,577 eligible women were screened between May 2000 and April 2003; 2,939 (9.6%) screen-positive women were investigated with colposcopy by nurses and 2,777 (9.1%) women had biopsy. CIN 1 was diagnosed in 1,778 women, CIN 2-3 lesions were found in 222, and there were 69 screen detected invasive cervical cancers. The detection rates of lesions per 1,000 screened women were 58.2 for CIN 1, 7.3 for CIN 2-3, and 2.3 for invasive cancer. The detection rate of high-grade lesions in our study was 2-3-fold higher than those observed in repeatedly screened populations in developed countries. 71% of women with CIN 1 and 80% of those with CIN 2-3 lesions accepted cryotherapy provided by nurses and surgical treatment by mid-level clinicians. Overall, 97 and 34 incident cervical cancer cases were observed in the intervention and control arms, respectively. The intervention arm accrued 124,144 person years and the control arm accrued 90,172 during the study period. The age standardized cervical cancer incidence rates were 92.4/100,000 person-years in the intervention and 43.1/100,000 in the control arms. In the screened arm, 35.0% of cases were in Stage I as opposed to none in the control arm. The preliminary findings from our study indicate that not only is a VIA-based screening programme feasible, safe and acceptable to a population in rural settings, it also results in early detection of cervical neoplasia.     

Neither one‐time negative screening tests nor negative colposcopy provides absolute reassurance against cervical cancer

A population sample of 10,049 women living in Guanacaste, Costa Rica, was recruited into a natural history of human papillomavirus (HPV) and cervical neoplasia study in 1993–1994. At the enrollment visit, we applied multiple state‐of‐the‐art cervical cancer screening methods to detect prevalent cervical cancer and to prevent subsequent cervical cancers by the timely detection and treatment of precancerous lesions. Women were screened at enrollment with 3 kinds of cytology (often reviewed by more than one pathologist), visual inspection and cervicography. Any positive screening test led to colposcopic referral and biopsy and/or excisional treatment of CIN2 or worse. We retrospectively tested stored specimens with an early HPV test (hybrid capture tube test) and for >40 HPV genotypes using a research PCR assay. We followed women typically 5–7 years and some up to 11 years. Nonetheless, 16 cases of invasive cervical cancer were diagnosed during follow‐up. Six cancer cases were failures at enrollment to detect abnormalities by cytology screening; 3 of the 6 were also negative at enrollment by sensitive HPV DNA testing. Seven cancers represent failures of colposcopy to diagnose cancer or a precancerous lesion in screen‐positive women. Finally, 3 cases arose despite attempted excisional treatment of precancerous lesions. Based on this evidence, we suggest that no current secondary cervical cancer prevention technologies applied once in a previously under‐screened population is likely to be 100% efficacious in preventing incident diagnoses of invasive cervical cancer. © 2009 UICC     

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

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 population‐specific age distribution of CIN2/3 should be an integral exercise in evaluating the effectiveness of a screening program.     

The influence of type‐specific human papillomavirus infections on the detection of cervical precancer and cancer: A population‐based study of opportunistic cervical screening in the United States

There are limited data on the prospective risks of detecting cervical precancer and cancer in United States (US) populations specifically where the delivery of opportunistic cervical screening takes place outside managed care and in the absence of organized national programs. Such data will inform the management of women with positive screening results before and after widespread human papillomavirus (HPV) vaccination and establishes a baseline preceding recent changes in US cervical cancer screening guidelines. Using data reported to the statewide passive surveillance systems of the New Mexico HPV Pap Registry, we measured the 3‐year HPV type‐specific cumulative incidence of cervical intraepithelial neoplasia grade 2 or more severe (CIN2+) and grade 3 or more severe (CIN3+) detected during real‐world health care delivery across a diversity of organizations, payers, clinical settings, providers and patients. A stratified sample of 47,541 cervical cytology specimens from a screening population of 379,000 women underwent HPV genotyping. Three‐year risks for different combinations of cytologic interpretation and HPV risk group ranged from <1% (for several combinations) to approximately 70% for CIN2+ and 55% for CIN3+ in women with high‐grade (HSIL) cytology and HPV16 infection. A substantial proportion of CIN2+ (35.7%) and CIN3+ (30.9%) were diagnosed following negative cytology, of which 62.3 and 78.2%, respectively, were high‐risk HPV positive. HPV16 had the greatest 3‐year risks (10.9% for CIN2+,8.0% for CIN3+) followed by HPV33, HPV31, and HPV18. Positive results for high‐risk HPV, especially HPV16, the severity of cytologic interpretation, and age contribute independently to the risks of CIN2+ and CIN3+.     

The current position and the future perspectives of cervical cancer screening

Cervical screening programs for detecting cancer and precancer have dramatically reduced the incidence and mortality rates of cervical cancer since the 1960s. The efficacy of the screening programs depends on participation and the accuracy of the screening tests. Unfortunately, the participation rates are suboptimal; more than half the women with cervical cancer have not or have only sporadically been screened. Increasing participation is the best way of maximizing the program’s benefit. Furthermore, cytology screening lacks high sensitivity for high-grade cervical intraepithelial neoplasia (≥CIN2). High-risk human papillomavirus (hrHPV) screening is more sensitive in the detection of cervical intraepithelial neoplasia than cytology screening, but less specific, so that additional triage testing is still mandatory. The aim of this article is to reflect on the efficacy of current cervical cancer screening and on promising future screening strategies with primary hrHPV testing and additional triage strategies for hrHPV-positive screening results.     

Differences in human papillomavirus type distribution in high‐grade cervical intraepithelial neoplasia and invasive cervical cancer in Europe

Knowledge of differences in human papillomavirus (HPV)‐type prevalence between high‐grade cervical intraepithelial neoplasia (HG‐CIN) and invasive cervical cancer (ICC) is crucial for understanding the natural history of HPV‐infected cervical lesions and the potential impact of HPV vaccination on cervical cancer prevention. More than 6,000 women diagnosed with HG‐CIN or ICC from 17 European countries were enrolled in two parallel cross‐sectional studies (108288/108290). Centralised histopathology review and standardised HPV‐DNA typing were applied to formalin‐fixed paraffin‐embedded cervical specimens dated 2001–2008. The pooled prevalence of individual HPV types was estimated using meta‐analytic methods. A total of 3,103 women were diagnosed with HG‐CIN and a total of 3,162 with ICC (median ages: 34 and 49 years, respectively), of which 98.5 and 91.8% were HPV‐positive, respectively. The most common HPV types in women with HG‐CIN were HPV16/33/31 (59.9/10.5/9.0%) and in ICC were HPV16/18/45 (63.3/15.2/5.3%). In squamous cell carcinomas, HPV16/18/33 were most frequent (66.2/10.8/5.3%), and in adenocarcinomas, HPV16/18/45 (54.2/40.4/8.3%). The prevalence of HPV16/18/45 was 1.1/3.5/2.5 times higher in ICC than in HG‐CIN. The difference in age at diagnosis between CIN3 and squamous cervical cancer for HPV18 (9 years) was significantly less compared to HPV31/33/‘other’ (23/20/17 years), and for HPV45 (1 year) than HPV16/31/33/‘other’ (15/23/20/17 years). In Europe, HPV16 predominates in both HG‐CIN and ICC, whereas HPV18/45 are associated with a low median age of ICC. HPV18/45 are more frequent in ICC than HG‐CIN and associated with a high median age of HG‐CIN, with a narrow age interval between HG‐CIN and ICC detection. These findings support the need for primary prevention of HPV16/18/45‐related cervical lesions.     

Comparison of HPV-based assays with Papanicolaou smears for cervical cancer screening in Morelos State,Mexico

Objective: To compare the performance of human papillomavirus (HPV) assays with conventional Pap cytology for cervical cancer (CC) screening in Mexico. Methods: Pap smears, self-collected vaginal specimens (SS) for HPV testing, and clinician-collected cervical specimens (CS) for HPV testing were obtained from 7868 women, aged 15–85 years old, attending CC screening at the Mexican Institute of Social Security (IMSS) between May and October, 1999. SS and CS specimens were screened for oncogenic HPV DNA by Hybrid Capture 2. Women who received cytological interpretations of atypical squamous cells of undetermined significance (ASCUS), and/or a positive HPV test were referred for colposcopy and histologic studies. The relative estimates for sensitivity, specificity and predictive values of each test were calculated using histological diagnoses of cervical intraepithelial neoplasia (CIN) grades 2 or 3, or CC histological diagnosis. Results: Oncogenic HPV detection rate was 11.6% for SS, and 9.3% for CS. Pap smear abnormalities were observed in 2.4% of the women. Of 1147 women who had at least one abnormal test result, 88.5% underwent colposcopy, and 101 biopsy-confirmed CIN2/3 or cancer cases were identified. The relative sensitivity estimates for the Pap test, SS and CS were 59.4% (95% CI: 49.2–68.9), 71.3% (95% CI: 61.3–79.6), and 93.1% (95% CI: 85.8–96.9), respectively, while the specificities were 98.3% (95% CI: 98.0–98.6), 89.2% (95% CI: 88.5–89.9), and 91.8% (95% CI: 91.2–92.4), respectively. The positive predictive values of Pap, SS and CS were 36.1, 9.1 and 14.9, the colposcopy referrals needed to detect a case of CIN2/3 or cancer were 2.8, 11.0 and 6.7, respectively. Discussion: Both HPV assays detected more cases of CIN2/3 or CC than Pap cytology alone. However, the HPV assays increased the number of colposcopy referrals. Our study suggests that HPV testing could be an effective way to improve the performance of CC screening.     

子宫颈抹片检查常规筛查宫颈组织、癌前病变或癌变在发展中国家门诊中的运用(英文)

Objective  

Papanicolou (Pap) smear screening has dramatically reduced the incidence of invasive cervical cancer worldwide. Pap smear screening is still not widely available in developing countries and therefore cannot be used as mass screening tool. This study was designed to establish the role of Pap smear as a routine investigation for females presented to gynecological department.     

Impact of utilizing p16INK4A immunohistochemistry on estimated performance of three cervical cancer screening tests

The histopathological diagnosis of cervical intraepithelial neoplasia grade 2,3 (CIN 2,3) is subjective and prone to variability. In our study, we analyzed the impact of utilizing a biomarker (p16(INK4A)) together with histopathology to refine the "gold standard" utilized for evaluating the performance of 3 different cervical cancer screening tests: cervical cytology, human papillomavirus (HPV) DNA testing and visual inspection with acetic acid (VIA). Cervical biopsies from 2 South African cervical cancer screening studies originally diagnosed by a single pathologist were reevaluated by a second pathologist and a consensus pathology diagnosis obtained. Immunohistochemical staining for p16(INK4A) was then performed. The estimated sensitivity of some cervical cancer screening tests was markedly impacted by the criteria utilized to define CIN 2,3. Use of routine histopathology markedly underestimated the sensitivity of both conventional cytology and HPV DNA testing compared to an improved gold standard of consensus pathology and p16(INK4A) positivity. In contrast, routine histopathology overestimated the sensitivity of VIA. Our results demonstrate that refining the diagnosis of CIN 2,3 through the use of consensus pathology and immunohistochemical staining for p16(INK4A) has an important impact on measurement of the performance of cervical cancer screening tests. The sensitivity of screening tests such as HPV DNA testing and conventional cytology may be underestimated when an imperfect gold standard (routine histopathology) is used. In contrast, the sensitivity of other tests, such as VIA, may be overestimated with an imperfect gold standard.     

女性下生殖道HPV感染与宫颈上皮内瘤变及宫颈癌关系的病理研究

目的：探讨女性下生殖道高危型人乳头状瘤病毒（high risk human papillomavirus,HR－HPV）感染与宫颈上皮内瘤变（cervical intraepithelial neoplasia,CIN）及宫颈癌的关系。方法：选择2013年2月－2015年4月我院收治的236例CIN及宫颈癌患者为观察组,进行下生殖道HPV（人乳头状瘤病毒）检测,分析CIN及宫颈癌与HPV感染的关系,并与对照组有宫颈炎但无CIN及宫颈癌的126例患者进行对比研究。结果：HR－HPV感染率随着患者CIN 的严重程度而升高,宫颈癌的HR－HPV感染率最高为91．89％,明显高于对照组差异具有统计学意义（P＜0．05）。HR－HPV双重感染率以及HR－HPV多重感染率与单一HR－HPV患者的病毒感染率相比较高,差异具有统计学意义（P＜0．05）。且患者随着病情的加重,单型、双重、多重HR－HPV感染率从CINⅠ期、CINⅡ期、CINⅢ期呈递增趋势。结论：HR－HPV感染及HR－HPV多重感染是导致宫颈上皮内瘤变及宫颈癌发生的重要诱因,对高危型 HPV 病毒的持续感染,及时的诊断并予以有效的治疗,能够阻滞癌前病变的发展,对于预防宫颈上皮内瘤变及宫颈癌,降低宫颈癌的死亡率具有重要临床意义。