| Background:Vulval Vulval cancer accounts for about 3%-5% of the female reproductive system tumor, the common symptoms are iterative chronic pruritus in vulvae,cauliflower-like lump, nodular bump,pain or bleeding of the bump as well as ulcers,some may undergo dysuria for advanced stage patients.Vaginal cancer accounts for about 1-2% of the female reproductive system tumor, it is mostly reported in posterior vaginal paries and the upper third part, the common symptoms are cauliflower-like lump,nodular bump as well as ulcers,abnormal vaginal bleeding and discharge etc. Although these two kinds of tumor are rare, the number of cases in our country increases year by year in recent years, which does great harm to female’s physical and mental health.Human papillomavirus (Human papillomavirus, HPV) is a circular double stranded DNA virus, constructed with double stranded DNA (about 8000 BPS) and outer capsid protein.lt is celleuar immortalizable and highly species specific,prone to epithelium.The virus DNA integrates with the DNA of the host cells.skin.Mucosa columnar epithelium and squamous epithelium is the most sensitive tissue.lt has been recognized that high-risk HPV infection is the main cause of cervical cancer,however,little research has been done about the relationship between vulva cancer, vagina cancer and HPV infection.Firstly,what’s the correlation between HPV infection and vulva cancer, vagina cancer,secondly,HPV subtype distribution for vulva cancer, vagina cancer,thirdly,whether the most common HPV subtype reported in Guangdong province consistents with other province or abroad,fourthly,how about the prognosis of HPV related vulva cancer and vaginal cancer,whether HPV is a effective indicator to predict tumor recurrence and whether HPV vaccine can be used to prevent vulva cancer and vagina cancer.Considering all the above questions, this project enrolled all the patients of vulva cancer and vagina cancer who are hospitalized in Obstetrics and Gynecology department of 10 major hospitals in Guangdong Province,classified HPV subtype and detected the viral load.Clinical pathology was also taken into consideration in order to make follow-up plan,the relationship between HPV infection and prognosis of vulva cancer and vagina cancer were explored, providing the theoretical basis for the application of vaccine in preventing vulva cancer and vagina cancer.Objective:To classify HPV subtype and detect the viral load combined with pathological results and clinical staging to investigate the situation and distribution of HPV subtype,as well as the correlation between viral load and cancer staging.Follow-up Follow-up was conducted for all the patients with vulva cancer or vagina cancer to investigate the recurrence rate and survival rate,probing if test for the HPV genotype can be used as a indicator of tumor recurrence.Methods:1、41 patients with primary vulva cancer and 18 patients with primary vagina cancer were enrolled from 10 hospitals in Guangdong province from September 2012 to September 2014.The vulva cancer patients were among 28 to 76 years old with a mean age of 55.14±12.04(S.D.) compared to 51.22±11.79(S.D.) in the vagina cancer group. HPV infection rate in the vaginal cancer group was 66.67%,2、The patients enrolled in the study were detected by HPV type, viral load testing and TCT.Hybrid capture Ⅱ tests(HC-Ⅱ) and HPV genotyping were used to detect the virus of HPV. The HPV genotyping is mainly to detect)were used to by flowing cytometry and fluorescence hybridization technology (Luminex surported by Shanghai Tellgen company)were detected 26 human papillomavirus subtypes.Hybrid capture 2 tests(HC2)were used to detect the virus load of high-risk HPV subtypes.3、The pathologic diagnosis were confirmed by more than two senior professors from Zhujiang Hospital, clinical staging is referred to the International Federation of gynecology and Obstetrics of vulva cancer (FIGO,2009),vagina cancer (FIGO, 2006).4、According to the requirements of the patients were followed up tumor.The follow-up included examination of the general symptoms and treatment of postoperative patients,postoperative complications,gynecological examination,the classification of HPV and the viral load testing, pelvic and urinary ultrasound examination, Thinprep cytologic testand, colposcopy and biopsy when necessary,recorded the adjuvant therapy, diet,recurrence time as well as survival condition. If patients died during follow-up, the time and cause of death were recorded.5、SPSS 19.0 was used for statistics analysis,chi square test and Fisher’s exact test were used for categorical measures, and the t-test was used for continuous measures. For all the tests a two-sided P value of less than 0.05 was considered to indicate statistical significance.Results:1、Among 41 vulvar cancers,65.85% were HPV positive, more than two subtypes of infection were 22 cases, single high-risk subtype infection in 5 cases, more than two subtype infection rate was 81.48%.The prevalence of HPV subtypewere88.89%(16,24/27),18.52%(52,5/27),14.81%(58,4/27),7.4%(31,2/27),3.7 %(33,1/27) respectively. The positive rate of HPV for 18 cases with vaginal cancer was 66.67%, Nine cases of vaginal cancer had multiple infection while 3 cases had single infection,10 cases were tested HPV-16 positive in vaginal cancer patients,HPV-52 (3/12,25%)、HPV-58 (2/12,16.67%)、HPV-33 (2/12,16.67)、 HPV-18 (1/12,8.33%) respectively.2、The average age of vulva cancer patients with HPV positive group had a mean age of 52.66±10.97(S.D.), compared to 61.36±12.71(S.D.) in the negative group, the age of the two groups had statistically significant (P=0.021).20 cases were tested positive for HPV infection among patients under 60 years of age,7 cases for the younger group, HPV negative group over 60 years old in 10 cases,60 cases under the age of 4, through statistical analysis over the age of 60 and the following were distributed in the two groups was not statistically significant(P=0.07). HPV positive group the average age of vaginal cancer patients in 49+3.17 years;HPV negative group the average age was 55.67+5.35 years old, the age of the two groups had no statistical significance (P=0.271).3、Squamous cell carcinoma was the most common pathological type of vulvar cancer, including 21 cases of keratinizing squamous cell carcinoma,11 cases were HPV positive, the positive rate of HPV was 52.4%,there were 11 cases of non-keratinizing squamous cell carcinoma,9 cases of HPV positive, the positive rate was 81.8%,there were 7 cases of the basal and verrucous carcinoma,6 cases of HPV positive, the positive rate was 85.7%, the positive rate was higher in non-keratinizing squamous and verrucous group,but there was no statistically significant difference between HPV negative group and positive group in pathological types and clinical stage and pathological differentiation (p>0.05). Among the18 cases of vagina cancer,13 cases were squamous cell carcinoma, accounting for about 72.22%, HPV positive group was 9 cases inpatients with squamous cell carcinoma of the vagina, the negative group was 4 cases,accounting for 69.23% of the patients with vaginal squamous cell carcinoma, the positive rate of vaginal squamous cell carcinoma HPV analysis may be relatively high from the pathologicaltype.4、Patients were divided into two groups according to the amount of viral DNA with a borderline point of 100 pg/ml,The low viral load group had a mean of 38.67 ±17.86(12 cases), high viral load load group 15 cases and the average viral load was 879.04+702 26pg/ml, two groups of viral load load had significant difference (P=0.001). The clinical staging of I-II during low load in 10 cases,11 cases of patients with high viral load,virus load was no statistically significant differences between high and low in the staging(P=0.228).2 cases of differentiation and low differentiation group with low load, high load in 3 cases; in high differentiation group and 10 patients with low load, high load in 12 patients, thelevel and degree of pathological differentiation and statistical analysis of viral load had no statistical difference (P=0.612).5、Within the follow-up period a total of 8 patients with recurrent vulvar cancer cases, including 2 cases of HPV positive group, HPV negative group 6 cases,2 years in the HPV positive group and HPV negative group patients relapse rate had statistical difference (P=0.012); HPVpositive group no patients died within 2 years,2 cases of death in patients with HPV negative group. No significant differences between the two groups of patients with recurrence rate and survival rate of vaginal cancer.6、After 3 months of low load group negative rate was 66.67%, high load group negative rate was 20%, two groups had statistical significance (P=0.006); after 6 months of low load groupnegative rate is 91.67%, high load group negative rate of 86.67%, the two groups had no statistical difference (P=0.586)。7、3 patients HC-Ⅱ examination after treatment was still positive in the27 cases of HPV positive with vulvar cancer:two patients after treatments were the same HPV subtypes with before treatments and the biopsy were suggested recurrence after follow-up of 11 months and 18 months respectively.The other one patient with preoperative subtypes were 52 and58, but postoperative subtypes were 33 and 56, although theviral load is positive, so far no recurrence. Three cases were HC-Ⅱ positives for Vaginal cancer patients:During the follow-up period,two patients who were the same HPV subtypes with before and after treatments were showed recurrence by biopsy.Another one patients who was diagnosed the endometrial adenocarcinoma was HC-Ⅱ positive after repeatedly review, but each subtype of HPV examination was not the same, no evidences were revealed the recurrence.Conclusions:1、The occurrence of vulvar and vaginal cancer may be associated with HPV infection. HPV infection is a major cause of vulvar cancer especially in younger patients. Our result indicates that HPV-16 is the most common type for vulva cancer and vagina cancer in Guangdong province, followed by HPV-52, HPV-58, HPV-33 etc, which provides the theoretical basis for the application of HPV vaccine in vulva and vagina cancer.2、The clinical stage and pathological differentiation shows no statistically significant differences between the HPV viral load groups.3、Squamous cell carcinoma was the most common pathological type of vulvar and vaginal cancer, the positive rate was higher in non-keratinizing squamous and verrucous subtypes,which showed that there was a connection between pathological types and HPV infection.4、Our experimental results shows that HPV-associated vulva cancer is likely to have better prognosis than the negative, more cases are required to evaluate this hypothesis.5、HPV genotyping was the better predicted recurrence for HPV infection of tumor than TCT.HPV genotype can be used as an indicator of tumor recurrence. |
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